Bone, Osteoporosis
15. May 2020
Generation of Gene-Corrected Functional Osteoclasts From Osteopetrotic Induced Pluripotent Stem Cells
Background: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene.
Methods: IMO iPSCs were generated from a patient carrying a homozygou…
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Journal:
Authors:
- Xian X,
- Moraghebi R,
- Löfvall H,
- Fasth A,
- Henriksen K,
- Richter J,
- Woods NB,
- Moscatelli I,
Endocrinology, Obesity
4. May 2020
Dose Frequency Optimization of the Dual Amylin and Calcitonin Receptor Agonist KBP-088: Long-Lasting Improvement in Food Preference and Body Weight Loss
Dual amylin and calcitonin receptor agonists (DACRAs) are novel candidates for treatment of type 2 diabetes and obesity because of their beneficial effects on body weight, blood glucose, insulin sensitivity, and food preference, at least short-term. DACRAs activate the receptors for a prolonged time…
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Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Endocrinology, Obesity, Type 2-Diabetes, Hepatic System
21. Apr 2020
The Calcitonin Receptor Plays a Major Role in Glucose Regulation as a Function of Dual Amylin and Calcitonin Receptor Agonist Therapy
Amylin treatment improves body weight and glucose control, although it is limited by a short action and need for high doses. Dual amylin and calcitonin receptor agonists (DACRAs) are dual amylin and calcitonin receptor agonists with beneficial effects beyond those of amylin. However, to what extent …
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Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Endocrinology, Obesity, Hepatic System
14. Apr 2020
The Dual Amylin and Calcitonin Receptor Agonist, KBP-066, Induces an Equally Potent Weight Loss Across a Broad Dose Range While Higher Doses May Further Improve Insulin Action
Pharmacological treatment with dual amylin and calcitonin receptor agonists (DACRAs) cause significant weight loss and improvement of glucose homeostasis. In this study, the maximally efficacious dose of the novel DACRA, KeyBiosciencePeptide (KBP)-066, was investigated. Two different rat models were…
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Journal:
Authors:
- Sonne N,
- Larsen AT,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Hepatic System, Non-Alcoholic Steatohepatitis, Non-Alcoholic Fatty Liver Disease
6. Jan 2020
Addition of trans fat and alcohol has divergent effects on atherogenic diet-induced liver injury in rodent models of steatohepatitis.
Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) are common causes of chronic liver disease. The overlap between ALD and NAFLD suggests the existence of metabolic steatohepatitis. Development of in vivo models that reflect various aspects of human steatohepatitis is essenti…
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Authors:
- Daniels SJ,
- Leeming DJ,
- Detlefsen S,
- Bruun MF,
- Hjuler ST,
- Henriksen K,
- Hein P,
- Krag A,
- Karsdal MA,
- Nielsen MJ,
- Brockbank S,
- curwys S,
Cardiovascular System, Central Nervous System
6. Nov 2019
A caspase-6-cleaved fragment of Glial Fibrillary Acidic Protein as a potential serological biomarker of CNS injury after cardiac arrest.
Blood levels of Glial Fibrillary Acidic protein (GFAP) reflect processes associated with different types of CNS injury. Evidence suggests that GFAP is cleaved by caspases during CNS injury, hence positioning GFAP fragments as potential biomarkers of injury-associated processes. We set out to develop…
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Journal:
Authors:
- Jonesco DS,
- Hassager C,
- Frydland M,
- Kjærgaard J,
- Karsdal MA,
- Henriksen K,
Rheumatology, Bone, Osteoporosis, Osteoarthritis, Biomarker position
30. Sep 2019
Biochemical markers in osteoarthritis with lessons learned from osteoporosis.
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th…
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Authors:
Obesity, Endocrinology
1. Jul 2019
The Dual Amylin and Calcitonin Receptor Agonist KBP-088 Induces Weight Loss and Improves Insulin Sensitivity Superior to Chronic Amylin Therapy
KBP-088 (KeyBiosciencePeptide 088) is a potent dual amylin and calcitonin receptor agonist (DACRA). DACRAs are known to elicit potent activity in terms of typical amylin-induced responses, such as reducing food intake and body weight. However, to what extent amylin infusion can mimic the effects of …
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Journal:
Authors:
- Larsen AT,
- Sonne N,
- Andreassen KV,
- Gehring K,
- Karsdal MA,
- Henriksen K,
Osteoporosis, Bone
10. Jun 2019
Hematopoietic stem cell-targeted neonatal gene therapy with a clinically applicable lentiviral vector corrects osteopetrosis in oc/oc mice.
Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by nonfunctional osteoclasts. Approximately 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. Gene therapy represents a potential alternative treatment …
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Journal:
Authors:
- Löfvall H,
- Rothe M,
- Schambach A,
- Henriksen K,
- Richter J,
- Moscatelli I,
Bone, Rheumatology, Osteoarthritis
5. Jun 2019
A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model
OBJECTIVES:
Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor a…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Lövfall H,
- Karsdal MA,
- Andreassen KV,
- Thudium CS,
- Henriksen K,
31. May 2019
Serum tau fragments as predictors of death or poor neurological outcome after out-of-hospital cardiac arrest
Background: Anoxic brain injury is the primary cause of death after resuscitation from out-of-hospital cardiac arrest (OHCA) and prognostication is challenging. The aim of this study was to evaluate the potential of two fragments of tau as serum biomarkers for neurological outcome.
Methods: Sing…
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Journal:
Authors:
- Grand J,
- Kjaergaard J,
- Nielsen N,
- Friberg H,
- Crongerg T,
- Bro-Jeppesen J,
- Karsdal MA,
- Nielsen HB,
- Frydland M,
- Henriksen K,
- Matsson N,
- Zetterberg H,
- Hassager C,
Endocrinology
23. May 2019
Circulating Biomarkers of Testosterone's Anabolic Effects on Fat-Free Mass
BACKGROUND:
Biomarkers that predict response to anabolic therapies could expedite the development of function promoting anabolic drugs. This study aimed to identify serum biomarkers that are responsive to testosterone administration and associated with increases in fat-free mass (FFM).
METHODS:
…
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Journal:
Authors:
- Huang G,
- Rocha GV,
- Pencina KM,
- Cox K,
- Krishnan V,
- Henriksen K,
- Mitchell P,
- Sissons SE,
- Li Z,
- Nedergaard AF,
- Karsdal MA,
- Sun S,
- Storer TW,
- Basaria S,
- Bhasin S,
Hepatic System, Non-Alcoholic Steatohepatitis
1. Mar 2019
Biochemical and histological characterisation of an experimental rodent model of non-alcoholic steatohepatitis - Effects of a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist and a glucagon-like peptide-1 analogue
BACKGROUND:
Non-alcoholic steatohepatitis (NASH) is a prevalent disease that is highly associated with the metabolic syndrome and type II diabetes. The development of in vivo models that reflect all nuances of the human NASH pathology is essential for drug discovery and development. We aimed to fur…
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Journal:
Authors:
- Daniels SJ,
- Leeming DJ,
- Detlefsen S,
- Bruun MF,
- Hjuler ST,
- Henriksen K,
- Hein P,
- Karsdal MA,
- Brockbank S,
- Cruwys S,
Rheumatology, Bone
28. Feb 2019
GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro
C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe…
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Journal:
Authors:
- Löfvall H,
- Katri A,
- Dabrowska A,
- Karsdal MA,
- Luo Y,
- He Y,
- Manon-Jensen T,
- Dziegiel MH,
- Bay-Jensen AC,
- Thudium CS,
- Henriksen K,
Rheumatology, Rheumatoid Arthritis, Bone
22. Feb 2019
Combining Naproxen and a Dual Amylin and Calcitonin Receptor Agonist improves pain and structural outcomes in the Collagen-Induced Arthritis rat model
BACKGROUND:
Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction w…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Löfvall H,
- Ding M,
- Karsdal MA,
- Andreassen KV,
- Schneider Thudium C,
- Henriksen K,
Rheumatology, Osteoarthritis
6. Nov 2018
A Novel High Sensitivity Type II Collagen Blood-Based Biomarker, PRO-C2, for Assessment of Cartilage Formation
N-terminal propeptide of type II collagen (PIINP) is a biomarker reflecting cartilage formation. PIINP exists in two main splice variants termed as type IIA and type IIB collagen NH₂-propeptide (PIIANP, PIIBNP). PIIANP has been widely recognized as a cartilage formation biomarker. However, the utili…
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Journal:
Authors:
- Luo Y,
- He Y,
- Gudmann NS,
- Henriksen K,
- Simonsen O,
- Ladel C,
- Michaels M,
- Mobasheri A,
- Karsdal MA,
- Bay-Jensen AC,
Bone, Extracellular Matrix Research
2. Oct 2018
Alterations in non-type I collagen biomarkers in osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a rare disorder of connective tissue caused by abnormalities in the synthesis or processing of type I collagen. Type I collagen is the most abundant type of collagen and is expressed in almost all connective tissues. Given that type I collagen interacts with other col…
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Journal:
Authors:
- Nicol L,
- Morar P,
- Wang Y,
- Henriksen K,
- Sun S,
- Karsdal MA,
- Smith R,
- Nagamani SCS,
- Shapiro J,
- Lee B,
- Orwoll E,
Central Nervous System, Alzheimer’s Disease
11. Apr 2018
Two novel blood-based biomarker candidates measuring degradation of tau are associated with dementia: a prospective study
BACKGROUND:
Truncated tau appears to be specifically related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer's disease (AD); however, the relevance of truncated Tau measurements in…
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Karsdal MA,
- Brix S,
- Henriksen K,
Bone, Extracellular Matrix Research, Osteoarthritis
10. Apr 2018
Osteoclasts degrade bone and cartilage knee joint compartments through different resorption processes
BACKGROUND:
Osteoclasts have been strongly implicated in osteoarthritic cartilage degradation, at least indirectly via bone resorption, and have been shown to degrade cartilage in vitro. The osteoclast resorption processes required to degrade subchondral bone and cartilage-the remodeling of which i…
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Journal:
Authors:
- Löfvall H,
- Newbould H,
- Karsdal MA,
- Dziegiel MH,
- Richter J,
- Henriksen K,
- Thudium CS,
Extracellular Matrix Research
29. Mar 2018
Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix
The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small c…
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Journal:
Authors:
- Kehlet SN,
- Willumsen N,
- Armbrecht G,
- Dietzel R,
- Brix S,
- Henriksen K,
- Karsdal MA,
Extracellular Matrix Research
1. Dec 2017
Objective Cognitive Impairment and Progression to Dementia in Women: The Prospective Epidemiological Risk Factor Study.
BACKGROUND:
Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer's disease have failed.
OBJECTIVES:
The objective of this study was to identify subgroups of individuals with objecti…
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Karsdal MA,
- Brix S,
- Henriksen K,
Bone, Osteoporosis
20. Jul 2017
Targeting NSG mice-engrafting cells with a clinically applicable lentiviral vector corrects osteoclasts in Infantile Malignant Osteopetrosis
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically…
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Journal:
Authors:
- Moscatelli I,
- Löfvall H,
- Schneider Thudium C,
- Rothe M,
- Montano C,
- Kertész Z,
- Sirin M,
- Schulz A,
- Schambach A,
- Henriksen K,
- Richter J,
Central Nervous System, Biomarker position
10. May 2017
Modifiable risk factors promoting neurodegeneration is associated with two novel brain degradation markers measured in serum
There has been limited success with blood-based biomarkers of neurodegeneration. One perceived reason is that blood has no direct contact to the brain. Recently developed blood-based biomarkers of tau-degradation have shown promise as potential tools for peripheral assessment of neurodegeneration; h…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Brix S,
- Workman CT,
- Nielsen HB,
- Christiansen C,
- Dragsbæk K,
- Neergaard JS,
Type 2-Diabetes, Obesity, Endocrinology
24. Apr 2017
The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Works as Adjunct to Metformin on Fasting Hyperglycemia and HbA1c in a Rat Model of Type 2 Diabetes
KBP-042 is a dual amylin and calcitonin receptor agonist that increases glucose tolerance and insulin action and reduces body weight in rat models of obesity and prediabetes. The objective of the present study was to 1) evaluate KBP-042 as a treatment of late-stage type 2 diabetes in a rat model and…
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Journal:
Authors:
- Hjuler ST,
- Gydesen S,
- Andreassen KV,
- Karsdal MA,
- Henriksen K,
Endocrinology, Type 2-Diabetes
7. Apr 2017
Metabolic Syndrome, Insulin Resistance, and Cognitive Dysfunction: Does Your Metabolic Profile Affect Your Brain?
Dementia and type 2 diabetes are both characterized by long prodromal phases, challenging the study of potential risk factors and their temporal relation. The progressive relation among metabolic syndrome, insulin resistance (IR), and dementia has recently been questioned, wherefore the aim of this …
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Nielsen HB,
- Brix S,
- Karsdal MA,
- Henriksen K,
Extracellular Matrix Research, Osteoarthritis
22. Mar 2017
Biomarker of extracellular matrix remodelling C1M and proinflammatory cytokine IL-6 are related to synovitis and pain in endstage knee osteoarthritis patients
Little is known about local and systemic biomarkers in relation to synovitis and pain in end-stage osteoarthritis (OA) patients. We investigated the associations between the novel extracellular matrix biomarker, C1M, and local and systemic interleukin 6 (IL-6) with synovitis and pain. Serum C1M, pla…
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Journal:
Authors:
- Radojcic MR,
- Thudium CS,
- Henriksen K,
- Tan K,
- Karlsten R,
- Dudley A,
- Chessell I,
- Karsdal MA,
- Bay-Jensen AC,
- Arbit E,
- Guermazi A,
Obesity
14. Mar 2017
Optimization of Tolerability and Efficacy of Dual Amylin and Calcitonin Receptor Agonist, KBP-089, through Dose Escalation and Combination with a GLP-1 Analogue
Amylin and GLP-1 agonism induce a well-known anorexic effect at dose initiation, which is managed by dose escalation. In this study, we investigated how to optimize tolerability, while maintaining efficacy of KBP-089. Furthermore, we tested the GLP-1 add-on potential of KBP-089 in HFD rats. KBP-089 …
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Journal:
Authors:
- Gydesen S,
- Andreassen KV,
- Hjuler ST,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Type 2-Diabetes
6. Mar 2017
Weight change and risk of hyperglycaemia in elderly women
BACKGROUND:
Hyperglycaemia increases the risk of type 2 diabetes, heart disease and stroke, and is influenced by weight. However, the impact of preceding weight change on blood glycemia levels in late-life is less well understood.
AIM:
We studied the interplay between weight change and risk of …
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Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Christiansen C,
- Karsdal MA,
- Beck-Nielsen H,
- Brix S,
- Henriksen K,
Osteoporosis
3. Feb 2017
Forced expression of human M-CSF in CD34+ cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro
OBJECTIVES:
Here, we tested the hypothesis that human M-CSF (hM-CSF) overexpressed in cord blood (CB) CD34+ cells would induce differentiation and survival of monocytes and osteoclasts in vitro and in vivo.
METHODS:
Human M-CSF was overexpressed in cord blood CD34+ cells using a lentiviral vect…
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Journal:
Authors:
- Montano Almendras CP,
- Thudium CS,
- Löfvall H,
- Moscatelli I,
- Schambach A,
- Henriksen K,
- Richter J,
Type 2-Diabetes
21. Jan 2017
A novel Dual Amylin and Calcitonin Receptor Agonist (DACRA), KBP-089, induces weight loss through a reduction in fat, but not lean mass, while improving food preference
BACKGROUND AND PURPOSE:
Obesity and associated co-morbidities, such as type 2 diabetes and non-alcoholic fatty liver disease, are major health challenges. Hence, there is an important need to develop weight loss therapies with the ability to reduce the co-morbidities.
EXPERIMENTAL APPROACH:
The…
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Journal:
Authors:
- Gydesen S,
- Hjuler ST,
- Freving Z,
- Andreassen KV,
- Sonne N,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Bone
14. Dec 2016
High throughput, quantitative analysis of human osteoclast differentiation and activity
Osteoclasts are multinuclear cells that degrade bone under both physiological and pathophysiological conditions. Osteoclasts are therefore a major target of osteoporosis therapeutics aimed at preserving bone. Consequently, analytical methods for osteoclast activity are useful for the development of …
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Journal:
Authors:
- Diepenhorst NA,
- Nowell CJ,
- Rueda P,
- Henriksen K,
- Pierce T,
- Cook AE,
- Pastoureau P,
- Sabatini M,
- Charman WN,
- Christopoulos A,
- Summers RJ,
- Sexton PM,
- Langmead CJ,
Central Nervous System, Alzheimer’s Disease
18. Nov 2016
Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patien…
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Journal:
Authors:
- O'Bryant SE,
- Mielke MM,
- Rissman RA,
- Lista S,
- Vanderstichele H,
- Zetterberg H,
- Lewczuk P,
- Posner H,
- Hall J,
- Johnson L,
- Fong YL,
- Luthman J,
- Jeromin A,
- Batrla-Utermann R,
- Villarreal A,
- Britton G,
- Snyder PJ,
- Henriksen K,
- Grammas P,
- Gupta V,
- Martins R,
- Hampel H,
Central Nervous System, Traumatic Brain Injury
15. Nov 2016
Serum tau fragments predict return to play in concussed professional ice hockey players
INTRODUCTION:
The diagnosis of sports-related concussion is mainly based on subjective clinical symptoms and neuropsychological tests. Thus, reliable brain injury biomarkers to assess when it is safe to return to play are highly desirable. The overall objective of this study was to evaluate the uti…
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Journal:
Authors:
- Shahim P,
- Linemann T,
- Inekci D,
- Karsdal MA,
- Blennow K,
- Tegner Y,
- Zetterberg H,
- Henriksen K,
Hepatic System, Type 2-Diabetes
20. Oct 2016
Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to anti-fibrotic therapy
There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic tria…
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Authors:
- Karsdal MA,
- Henriksen K,
- Nielsen MJ,
- Byrjalsen I,
- Leeming DJ,
- Gardner SD,
- Goodman ZD,
- Patel K,
- Krag A,
- Christiansen C,
- Schuppan D,
Bone, Osteoporosis
1. Oct 2016
A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D
This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D …
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Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Andersen JR,
- Bihlet AR,
- Russo LA,
- Alexandersen P,
- Valter I,
- Qvist P,
- Lau E,
- Riis BJ,
- Christiansen C,
- Karsdal MA,
- SMC021 investigators,
Type 2-Diabetes
15. Sep 2016
Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women: Challenging the current definition
The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) a…
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Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Laursen JM,
- Hansen HB,
- Christiansen C,
- Beck-Nielsen H,
- Karsdal MA,
- Brix S,
- Henriksen K,
Type 2-Diabetes
8. Sep 2016
Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes
AIMS/HYPOTHESIS:
The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of pro…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Genovese F,
- Leeming DJ,
- Nielsen MJ,
- Riis BJ,
- Christiansen C,
- Byrjalsen I,
- Schuppan D,
Bone
30. Aug 2016
Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies
For several decades, serological biomarkers of neuromuscular diseases as dystrophies, myopathies and myositis have been limited to routine clinical biochemistry panels. Gauging the pathological progression is a prerequisite for proper treatment and therefore identifying accessible, easy to monitor b…
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Journal:
Authors:
- Arvanitidis A,
- Henriksen K,
- Karsdal MA,
- Nedergaard AF,
Bone
19. Aug 2016
Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy
Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We …
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Journal:
Authors:
- Thudium CS,
- Moscatelli I,
- Löfvall H,
- Kertész Z,
- Montano C,
- Bjurström CF,
- Karsdal MA,
- Schulz AS,
- Richter J,
- Henriksen K,
Endocrinology, Type 2-Diabetes
1. Aug 2016
The dual amylin- and calcitonin-receptor agonist KBP-042 increases insulin sensitivity and induces weight loss in rats with obesity
OBJECTIVE:
In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 µg/kg-10 µg/kg) compared with saline-treated and pair-fed controls.
METHODS:
Rats with obesity received daily s.c…
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Journal:
Authors:
- Hjuler ST,
- Gydesen S,
- Andreassen KV,
- Pedersen SL,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Osteoporosis, Bone
1. Jun 2016
Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice
In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery …
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Journal:
Authors:
- Wendelboe MH,
- Thomsen JS,
- Henriksen K,
- Vegger JB,
- Brüel A,
Alzheimer’s Disease
1. Mar 2016
Late-Life Risk Factors for All-Cause Dementia and Differential Dementia Diagnoses in Women: A Prospective Cohort Study
Since the first evidence of a decline in dementia incidence was reported in 2011, the focus on modifiable risk factors has increased. The possibility of risk factor intervention as a prevention strategy has been widely discussed; however, further evidence in relation to risk factors is still needed.…
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Journal:
Authors:
Endocrinology
7. Dec 2015
Collagen Type III and VI Turnover in Response to Long-Term Immobilization
BACKGROUND:
Muscle mass and function are perturbed by immobilization and remobilization. When muscle mass changes, the quality and quantity of the extracellular matrix protein, particularly the collagens, change with it. In this study, we investigated the temporal profile of three peptide biomarker…
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Journal:
Authors:
- Sun S,
- Henriksen K,
- Karsdal MA,
- Byrjalsen I,
- Rittweger J,
- Armbrecht G,
- Belavý DL,
- Felsenberg D,
- Nedergaard AF,
Endocrinology
6. Dec 2015
Collagen fragment biomarkers as serological biomarkers of lean body mass - a biomarker pilot study from the DAHANCA25B cohort and matched controls
BACKGROUND:
Loss of muscle mass and function is an important complication to ageing and a range of pathologies, including, but not restricted to, cancer, organ failures, and sepsis. A number of interventions have been proposed ranging from exercise to anabolic pharmacological therapy, with varying …
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Journal:
Authors:
- Nedergaard A,
- Dalgas U,
- Primdahl H,
- Johansen J,
- Overgaard J,
- Overgaard K,
- Henriksen K,
- Karsdal MA,
- Lønbro S,
Bone, Osteoporosis
27. Oct 2015
Role of biochemical markers in the management of osteoporosis
Estrogen and bone health form a cornerstone of osteoporosis management. Diagnosis of osteoporosis is performed using bone mineral density (BMD), despite the limitations associated with this. Within the last 25 years, numerous bone turnover markers (BTM) have been developed, and this has led to a mar…
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Authors:
Bone, Osteoporosis
8. Sep 2015
Null mutation of chloride channel 7 (Clcn7) impairs dental root formation but does not affect enamel mineralization
ClC-7, located in late endosomes and lysosomes, is critical for the function of osteoclasts. Secretion of Cl(-) by the ruffled border of osteoclasts enables H(+) secretion by v-H(+)-ATPases to dissolve bone mineral. Mice lacking ClC-7 show altered lysosomal function that leads to severe lysosomal st…
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Journal:
Authors:
- Guo J,
- Bervoets TJ,
- Henriksen K,
- Everts V,
- Bronckers AL,
Endocrinology, Type 2-Diabetes
5. Sep 2015
KBP-042 improves bodyweight and glucose homeostasis with indices of increased insulin sensitivity irrespective of route of administration
KBP-042 is a synthetic peptide dual amylin- and calcitonin-receptor agonist (DACRA) developed to treat type 2 diabetes by inducing a significant weight loss while improving glucose homeostasis. In this study the aim was to compare two different formulations: An oral formulation (1mg/kg) to subcutane…
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Journal:
Authors:
- Hjuler ST,
- Andreassen KV,
- Gydesen S,
- Karsdal MA,
- Henriksen K,
Alzheimer’s Disease, Central Nervous System
10. Jul 2015
Serum fragments of Tau for the differential diagnosis of Alzheimer's disease
Differential diagnosis of AD is still a challenge due to overlapping features with other types of dementia. Biomarkers for the differential diagnosis of AD can improve the diagnostic value of the disease and ensure an appropriate treatment of patients. The aim of this study was to evaluate the poten…
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Journal:
Authors:
- Inekci D,
- Henriksen K,
- Linemann T,
- Karsdal MA,
- Habib A,
- Bisgaard, C,
- Eriksen FB,
- Vilholm OJ,
Bone, Osteoporosis
1. Jul 2015
Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation
Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losin…
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Journal:
Authors:
- McGee-Lawrence M,
- Buckendahl P,
- Carpenter C,
- Henriksen K,
- Vaughan M,
- Donahue S,
Alzheimer’s Disease, Central Nervous System
11. Jun 2015
Relationship between serum levels of tau fragments and clinical progression of Alzheimer's disease
Enzyme-generated fragments of tau have been linked to neuronal death and may serve as serum biomarkers of cognitive loss. Two competitive ELISAs detecting an ADAM10-generated fragment (Tau-A) or a caspase-3-generated fragment (Tau-C) were measured in baseline serum samples from patients with mild to…
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Authors:
Central Nervous System, Alzheimer’s Disease
11. May 2015
Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research
The lack of readily available biomarkers is a significant hindrance toward progressing to effective therapeutic and preventative strategies for Alzheimer's disease (AD). Blood-based biomarkers have potential to overcome access and cost barriers and greatly facilitate advanced neuroimaging and cerebr…
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Journal:
Authors:
- O'Bryant SE,
- Gupta V,
- Henriksen K,
- Edwards M,
- Jeromin A,
- Lista S,
- Bazenet C,
- Soares H,
- Lovestone S,
- Hampel H,
- Montine T,
- Blennow K,
- Carrillo M,
- Graff-Radford N,
- Laske C,
- Breteler M,
- Shaw L,
- Trojanowski JQ,
- Schupf N,
- Rissman RA,
- Fagan AM,
- Oberoi P,
- Umek R,
- Weiner MW,
- Grammas P,
- Posner H,
- Martins R,
- STAR-B and BBBIG working groups,
Alzheimer’s Disease, Central Nervous System
11. May 2015
The potential of pathological protein fragmentation in blood-based biomarker development for dementia - with emphasis on Alzheimer's disease
The diagnosis of dementia is challenging and early stages are rarely detected limiting the possibilities for early intervention. Another challenge is the overlap in the clinical features across the different dementia types leading to difficulties in the differential diagnosis. Identifying biomarkers…
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Journal:
Authors:
- Inekci D,
- Jonesco DS,
- Kennard S,
- Karsdal MA,
- Henriksen K,
Bone, Osteoporosis
10. May 2015
Novel targets for the prevention of osteoporosis - lessons learned from studies of metabolic bone disorders
Osteoporosis is a major health care problem, and whereas efficacious treatments for vertebral fracture reduction are available for osteoporosis patients, these therapies are still limited with respect to capacity for restoration of bone loss, as well as efficacy on non-vertebral fractures, such as h…
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Endocrinology, Type 2-Diabetes
1. May 2015
Lessons learned from the clinical development of oral peptides
The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken t…
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Journal:
Authors:
- Karsdal MA,
- Riis BJ,
- Mehta N,
- Stern W,
- Arbit E,
- Christiansen C,
- Henriksen K,
Extracellular Matrix Research
9. Oct 2014
Measurement of a MMP-2 degraded Titin fragment in serum reflects changes in muscle turnover induced by atrophy
PURPOSE:
In this study we sought to determine whether a Titin peptide fragment can serve as a clinical biomarker for changes in muscle mass.
METHODS:
Mass spectrometry was used to identify Titin fragment in urine. An antibody against this Titin sequence was raised and used to develop a competit…
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Journal:
Authors:
- Sun S,
- Henriksen K,
- Karsdal MA,
- Armbrecht G,
- Belavý DL,
- Felsenberg D,
- Rittweger J,
- Wang Y,
- Zheng Q,
- Nedergaard AF,
Endocrinology, Type 2-Diabetes
14. Aug 2014
Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats
We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present st…
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Journal:
Authors:
- Feigh M,
- Hjuler ST,
- Andreassen KV,
- Gydesen S,
- Ottosen I,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Endocrinology, Type 2-Diabetes
31. Jul 2014
A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats
The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced obes…
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Journal:
Authors:
- Andreassen KV,
- Feigh M,
- Hjuler ST,
- Gydesen S,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Bone
22. Jul 2014
A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation
Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating that…
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Journal:
Authors:
- Thudium CS,
- Moscatelli I,
- Flores C,
- Thomsen JS,
- Brüel A,
- Gudmann NS,
- Hauge EM,
- Karsdal MA,
- Richter J,
- Henriksen K,
Type 2-Diabetes, Obesity, Endocrinology
6. May 2014
A Novel Oral Dual Amylin and Calcitonin Receptor Agonist (KBP-042) Exerts Anti-Obesity and Anti-Diabetic Effects in Rats
The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced obes…
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Journal:
Authors:
- Andreassen KV,
- Feigh M,
- Hjuler ST,
- Gydesen S,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Osteoarthritis
19. Mar 2014
The active form of MMP-3 is a marker of synovial inflammation and cartilage turnover in inflammatory joint diseases
BACKGROUND:
Matrix metalloproteinase-3 (MMP-3) plays an important role in the pathology of rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Measurement of active MMP-3 in clinical samples could provide information about progression of rheumatoid diseases, and potentially response to treat…
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Journal:
Authors:
- Sun S,
- Bay-Jensen AC,
- Karsdal MA,
- Siebuhr AS,
- Zheng Q,
- Maksymowych WP,
- Christiansen TG,
- Henriksen K,
Endocrinology, Type 2-Diabetes
18. Mar 2014
Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias
Salmon calcitonin (sCT) and human calcitonin (hCT) are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(a)R) with respect to activation of cAMP signaling, β-arrestin recruitment, l…
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Journal:
Authors:
- Andreassen KV,
- Hjuler ST,
- Furness SG,
- Sexton PM,
- Christopoulos A,
- Nosjean O,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis
6. Feb 2014
The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?
Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, affecting bone, cartilage and synovium that thereby presents multiple targets for treatment. This manuscript wil…
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Journal:
Authors:
- Karsdal MA,
- Bay-Jensen AC,
- Lories RJ,
- Abramson S,
- Spector T,
- Pastoureau P,
- Christiansen C,
- Attur M,
- Henriksen K,
- Goldring SR,
- Kraus V,
Rheumatology, Rheumatoid Arthritis
27. Jan 2014
Rheumatoid arthritis - A case for Personalized Health Care?
Ethical, clinical, and economic considerations highlight the pressing need to advance the identification of optimal treatments for each individual patient. Personalized health care (PHC) may provide a significant benefit in the treatment of a number of clinical indications characterized by costly th…
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Journal:
Authors:
- Karsdal MA,
- Bay-Jensen AC,
- Henriksen K,
- Christiansen C,
- Genant HK,
- Chamberlain C,
- Platt A,
Rheumatology, Osteoarthritis
22. Jan 2014
Osteoarthritis--a case for personalized health care?
For both economic and ethical reasons, identification of the optimal treatment for each individual patient is a pressing concern, not only for the patients and their physician, but also health care payers and the pharmaceutical industry. In the field of osteoarthritis (OA) this is of particular rele…
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Journal:
Authors:
- Karsdal MA,
- Christiansen C,
- Ladel C,
- Henriksen K,
- Kraus VB,
- Bay-Jensen AC,
Bone
15. Jan 2014
Osteoclast-derived coupling factors in bone remodeling
In the bone remodeling process that takes place throughout the skeleton at bone multicellular units, intercellular communication processes are crucial. The osteoblast lineage has long been known to program osteoclast formation and hence resorption, but the preservation of bone mass and integrity req…
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Journal:
Authors:
- Henriksen K,
- Karsdal MA,
- Martin TJ,
10. Jan 2014
Developing novel blood-based biomarkers for Alzheimer's disease
Alzheimer's disease is the public health crisis of the 21st century. There is a clear need for a widely available, inexpensive and reliable method to diagnosis Alzheimer's disease in the earliest stages, track disease progression, and accelerate clinical development of new therapeutics. One avenue o…
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Journal:
Authors:
- Fillit HM,
- Weiner MW,
- Shineman DW,
- Bain LJ,
- West T,
- Ward M,
- Trushina E,
- Teeling J,
- Soares H,
- Sjøgren M,
- Sarasa M,
- O'Bryant SE,
- Mielke MM,
- Lovestone S,
- Jeromin A,
- Henriksen K,
- Grodstein F,
- Carrillo MC,
- Snyder HM,
Central Nervous System, Alzheimer’s Disease
8. Jan 2014
The future of blood-based biomarkers for Alzheimer's disease
Treatment of Alzheimer's disease (AD) is significantly hampered by the lack of easily accessible biomarkers that can detect disease presence and predict disease risk reliably. Fluid biomarkers of AD currently provide indications of disease stage; however, they are not robust predictors of disease pr…
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Journal:
Authors:
- Henriksen K,
- O'Bryant SE,
- Hampel H,
- Trojanowski JQ,
- Montine TJ,
- Jeromin A,
- Blennow K,
- Lönneborg A,
- Wyss-Coray T,
- Soares H,
- Bazenet C,
- Sjögren M,
- Hu W,
- Lovestone S,
- Karsdal MA,
- Weiner MW,
- Blood-Based Biomarker Interest Group,
Rheumatology
12. Dec 2013
Type VI collagen turnover-related peptides-novel serological biomarkers of muscle mass and anabolic response to loading in young men
BACKROUND:
Immobilization-induced loss of muscle mass is a complex phenomenon with several parallels to sarcopenic and cachectic muscle loss. Muscle is a large organ with a protein turnover that is orders of magnitude larger than most other tissues. Thus, we hypothesize that muscle loss and regain …
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Journal:
Authors:
- Nedergaard A,
- Sun S,
- Karsdal MA,
- Henriksen K,
- Kjær M,
- Lou Y,
- He Y,
- Zheng Q,,
- Suetta C,
Bone
11. Dec 2013
Osteoclasts are not crucial for hematopoietic stem cell maintenance in adult mice
The osteoclast is vital for establishment of normal hematopoiesis in the developing animal. However, its role for maintenance of hematopoiesis in adulthood is more controversial. To shed more light on this process, we transplanted hematopoietic stem cells from two osteopetrotic mouse models, with la…
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Journal:
Authors:
- Flores C,
- Moscatelli I,
- Thudium CS,
- Gudmann NS,
- Thomsen JS,
- Brüel A,
- Karsdal MA,
- Henriksen K,
- Richter J,
Bone
5. Nov 2013
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorpt…
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Journal:
Authors:
- Moscatelli I,
- Thudium CS,
- Flores C,
- Schulz A,
- Askmyr M,
- Gudmann NS,
- Andersen NM,
- Porras O,
- Karsdal MA,
- Villa A,
- Fasth A,
- Henriksen K,
- Richter J,
Rheumatology
16. Oct 2013
Musculoskeletal ageing and primary prevention
Loss of musculoskeletal mass and function is a natural ageing trait, reinforced by an unhealthy life style. Loss of bone (osteoporosis) and muscle (sarcopaenia) are conditions whose prevalence are increasing because of the change in population distribution in the western world towards an older mean …
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Journal:
Authors:
- Nedergaard A,
- Henriksen K,
- Karsdal MA,
- Christiansen C,
Rheumatology, Osteoarthritis
6. Oct 2013
The development and characterization of an ELISA specifically detecting the active form of cathepsin K
OBJECTIVE:
Cathepsin K plays essential roles in bone resorption and is intensely investigated as a therapeutic target for the treatment of osteoporosis. Hence an assessment of the active form of cathepsin K may provide important biological information in metabolic bone diseases, such as osteoporosi…
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Journal:
Authors:
- Sun S,
- Karsdal MA,
- Bay-Jensen AC,
- Sørensen MG,
- Zheng Q,
- Dziegiel MH,
- Maksymowych WP,
- Henriksen K,
Biomarker position
18. Aug 2013
Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways -- implications for modern clinical chemistry
The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…
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Journal:
Authors:
Bone
29. Jul 2013
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34+ cells restores osteoclast function in infantile malignant osteopetrosis
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorpt…
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Journal:
Authors:
- Moscatelli I,
- Thudium CS,
- Flores C,
- Schulz A,
- Askmyr M,
- Gudmann KN,
- Andersen NM,
- Porras O,
- Karsdal MA,
- Villa A,
- Fasth A,
- Henriksen K,
- Richter J,
Bone
13. Jul 2013
Autosomal dominant osteopetrosis revisited: lessons from recent studies
Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the …
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Journal:
Authors:
- Bollerslev J,
- Henriksen K,
- Nielsen MF,
- Brixen K,
- Van Hul W,
Rheumatology, Rheumatoid Arthritis
31. May 2013
Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways - implications for modern clinical chemistry
The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…
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Journal:
Authors:
Endocrinology
29. May 2013
Menopause, estrogens and frailty
The controversy surrounding the results from the Women's Health Initiative (WHI) trials published a decade ago caused a significant decline in the use of menopausal hormone replacement therapy. However, these results have been vehemently contested and several lines of evidence suggest that in perime…
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Journal:
Authors:
- Nedergaard A,
- Henriksen K,
- Karsdal MA,
- Christiansen C,
Central Nervous System, Alzheimer’s Disease
22. May 2013
An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function
OBJECTIVE:
Alzheimer's disease (AD) is a devastating neurological disease characterized by pathological proteolytic cleavage of tau protein, which appears to initiate death of the neurons. The objective of this study was to investigate whether a proteolytic fragment of the tau protein could serve a…
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Journal:
Authors:
- Henriksen K,
- Wang Y,
- Sørensen MG,
- Barascuk N,
- Suhy J,
- Pedersen JT,
- Duffin KL,
- Dean RA,
- Pajak M,
- Christiansen C,
- Zheng Q,
- Karsdal MA,
Hepatic System, Alcoholic Liver Disease
19. Apr 2013
The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters
AIM:
The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3).
METHODS:
The monoclonal antibody wa…
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Journal:
Authors:
- Nielsen MJ,
- Nedergaard AF,
- Sun S,
- Veidal SS,
- Larsen L,
- Zheng Q,
- Suetta C,
- Henriksen K,
- Christiansen C,
- Karsdal MA,
- Leeming DJ,
Extracellular Matrix Research
11. Mar 2013
Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure
Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive ti…
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Journal:
Authors:
- Karsdal MA,
- Nielsen MJ,
- Sand JM,
- Henriksen K,
- Genovese F,
- Bay-Jensen AC,
- Adamkewicz JI,
- Christiansen C,
- Leeming DJ,
Endocrinology
4. Mar 2013
Serological muscle loss biomarkers: an overview of current concepts and future possibilities
BACKGROUND:
The skeletal muscle mass is the largest organ in the healthy body, comprising 30-40 % of the body weight of an adult man. It confers protection from trauma, locomotion, ventilation, and it represents a "sink" in glucose metabolism and a reservoir of amino acids to other tissues such as …
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Journal:
Authors:
- Nedergaard A,
- Karsdal MA,
- Sun S,
- Henriksen K,
Bone
3. Mar 2013
Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1-31)NH(2)] in postmenopausal women with osteoporosis
CONTEXT:
Treatment of osteoporosis with subcutaneous (SC) injections of rhPTH(1-34) or rhPTH(1-84) is associated with significant improvements in BMD and reductions in osteoporotic fractures. However, subcutaneous injections can be associated with discomfort and thus deteriorating compliance.
OB…
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Journal:
Authors:
- Henriksen K,
- Andersen JR,
- Riis BJ,
- Mehta N,
- Tavakkol R,
- Alexandersen P,
- Byrjalsen I,
- Valter I,
- Nedergaard BS,
- Teglbjaerg CS,
- Stern W,
- Sturmer A,
- Mitta S,
- Nino AJ,
- Fitzpatrick LA,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
14. Feb 2013
Investigation of chondrocyte hypertrophy and cartilage calcification in a full-depth articular cartilage explants model
Articular cartilage deterioration, which includes cartilage degradation and chondrocyte hypertrophy, is a hallmark of degenerative joint diseases (DJD). Chondrocyte hypertrophy is initiated in the deep layer of the cartilage; thus, a robust explants model for investigation of hypertrophy should incl…
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Journal:
Authors:
- Chen-An P,
- Andreassen KV,
- Henriksen K,
- Karsdal MA,
- Bay-Jensen AC,
Endocrinology, Type 2-Diabetes
4. Feb 2013
Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats
OBJECTIVE:
Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects …
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Journal:
Authors:
- Feigh M,
- Andreassen KV,
- Hjuler ST,
- Nielsen RH,
- Christiansen C,
- Henriksen K,
- Karsdal MA,
Rheumatology, Osteoarthritis
18. Dec 2012
The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet?
The female predominance of polyarticular osteoarthritis (OA), and in particular the marked increase of OA in women after the menopause points to a likely involvement of female sex hormones in the maintenance of cartilage homeostasis. This perception has inspired many research groups to investigate t…
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Journal:
Authors:
Central Nervous System, Alzheimer’s Disease
12. Dec 2012
Will posttranslational modifications of brain proteins provide novel serological markers for dementias?
Drug development for dementias is significantly hampered by the lack of easily accessible biomarkers. Fluid biomarkers of dementias provide indications of disease stage, but have little prognostic value, cannot detect early pathological changes, and can only be measured in CSF (cerebrospinal fluid) …
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Journal:
Authors:
- Wang Y,
- Sørensen MG,
- Zheng Q,
- Zhang C,
- Karsdal MA,
- Henriksen K,
Endocrinology, Type 1-Diabetes
10. Oct 2012
Future detection and monitoring of diabetes may entail analysis of both β-cell function and volume: how markers of β-cell loss may assist
Disease heterogeneity is as major issue in Type II Diabetes Mellitus (T2DM), and this patient inter-variability might not be sufficiently reflected by measurements of glycated haemoglobin (HbA1c).Β-cell dysfunction and β-cell death are initiating factors in development of T2DM. In fact, β-cells are …
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Andreassen KV,
- Hjuler ST,
- Feigh M,
- Bay-Jensen AC,
- Zheng Q,
- Henriksen K,
- Karsdal MA,
Endocrinology, Type 2-Diabetes
16. Sep 2012
Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats
BACKGROUND AND PURPOSE:
Oral salmon calcitonin (sCT), a dual-action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet-induced obese rats. Here, we have evaluated the anti-diabetic efficacy of oral sCT using parameters of glycaemic control and beta-cell morphology in male …
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Journal:
Authors:
- Feigh M,
- Andreassen KV,
- Neutzsky-Wulff AV,
- Petersen ST,
- Hansen C,
- Bay-Jensen AC,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Henriksen K,
- Karsdal MA,
Bone
16. Sep 2012
A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts
Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium was c…
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Journal:
Authors:
- Henriksen K,
- Andreassen KV,
- Thudium CS,
- Gudmann KN,
- Moscatelli I,
- Crüger-Hansen CE,
- Schulz AS,
- Dziegiel MH,
- Richter J,
- Karsdal MA,
- Neutzsky-Wulff AV,
Rheumatology, Osteoarthritis
1. Jul 2012
The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage
OBJECTIVE:
Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. W…
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Journal:
Authors:
- Chen-An P,
- Andreassen KV,
- Henriksen K,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Spondyloarthropathies
30. May 2012
Investigation of two novel biochemical markers of inflammation, matrix metalloproteinase and cathepsin generated fragments of C-reactive protein, in patients with ankylosing spondylitis
OBJECTIVES:
Ankylosing spondylitis (AS) is a chronic inflammation of the spine and the sacroiliac joints. Current markers of inflammation, such as C-reactive protein (CRP), are reflecting the production of an acute phase reactant rather than tissue specific inflammation, but the use of CRP as a dia…
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Journal:
Authors:
- Skjøt-Arkil H,
- Schett G,
- Zhang C,
- Larsen DV,
- Wang Y,
- Zheng Q,
- Larsen MR,
- Nawrocki A,
- Bay-Jensen AC,
- Henriksen K,
- Christiansen C,
- Alexandersen P,
- Leeming DJ,
- Karsdal MA,
Bone
5. Apr 2012
Generation of human osteoclasts from peripheral blood
Osteoclasts are multi-nucleated cells that have the unique ability to resorb calcified bone matrix. They derive from haematopoietic precursor cells, and can be generated in vitro by stimulation of peripheral blood mononuclear cells with the cytokines M-CSF and RANKL. In this chapter, we describe the…
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Journal:
Authors:
- Henriksen K,
- Karsdal MA,
- Taylor A,
- Tosh D,
- Coxon FP,
Hepatic System, Alcoholic Liver Disease
5. Apr 2012
Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology
AIM:
To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes.
METHODS:
A monoclonal antibody against the sequence RLRSSVPGV-citrullin…
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Journal:
Authors:
- Vassiliadis E,
- Oliveira CP,
- Alvares-da-Silva MR,
- Zhang C,
- Carrilho FJ,
- Stefano JT,
- Rabelo F,
- Pereira L,
- Kappel CR,
- Henriksen K,
- Veidal SS,
- Vainer B,
- Duffin KL,
- Christiansen C,
- Leeming DJ,
- Karsdal MA,
Bone, Osteoporosis
13. Mar 2012
Disruption of the V-ATPase functionality as a way to uncouple bone formation and resorption - a novel target for treatment of osteoporosis
The unique ability of the osteoclasts to resorb the calcified bone matrix is dependent on secretion of hydrochloric acid. This process is mediated by a vacuolar H+ ATPase (V-ATPase) and a chloride-proton antiporter. The structural subunit of the V-ATPase, a3, is highly specific for osteoclasts, and …
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Journal:
Authors:
- Thudium CS,
- Jensen VK,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis
15. Feb 2012
Mice over-expressing salmon calcitonin have strongly attenuated osteoarthritic histopathological changes after destabilization of the medial meniscus
OBJECTIVE:
Calcitonin is well-known for its inhibitory actions on bone-resorbing osteoclasts and recently potential beneficial effects on cartilage were shown. We investigated effects of salmon calcitonin (sCT) on the articular cartilage and bone, after destabilization of the medial meniscus (DMM) …
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Journal:
Authors:
- Sondergaard BC,
- Catala-Lehnen P,
- Huebner AK,
- Bay-Jensen AC,
- Schinke T,
- Henriksen K,
- Schilling S,
- Haberland M,
- Nielsen RH,
- Amling M,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
10. Feb 2012
Tumor necrosis factor-α and receptor activator of nuclear factor-κB ligand augment human macrophage foam-cell destruction of extracellular matrix through protease-mediated processes
By secreting proteases such as cathepsins and matrix metalloproteinases (MMPs), macrophage foam cells may be a major cause of ruptured atherosclerotic plaques. The aims of the present study were to investigate in vitro role of human macrophage foam cells in degrading type I collagen, a major compone…
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Journal:
Authors:
- Skjøt-Arkil H,
- Barascuk N,
- Larsen L,
- Dziegiel M,
- Henriksen K,
- Karsdal MA,
Bone, Osteoporosis
11. Dec 2011
Glucocorticoids exert context-dependent effects on cells of the joint in vitro
INTRODUCTION:
Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthri…
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Journal:
Authors:
- Madsen SH,
- Andreassen KV,
- Christensen ST,
- Karsdal MA,
- Sverdrup FM,
- Bay-Jensen AC,
- Henriksen K,
Bone
7. Nov 2011
Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options
Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry-based measurements of bone mineral density. However, within the…
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Authors:
Extracellular Matrix Research
16. Oct 2011
Serological biochemical markers of surrogate efficacy and safety as a novel approach to drug repositioning
How do pharmaceutical companies find new uses for old or failed drugs? Is there a way to 'manage serendipity' at the very first stage of identifying compounds that could be developed into new drugs? Several approaches are now being pursued by various companies that are dedicated to drug repositionin…
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Authors:
Endocrinology, Type 2-Diabetes
13. Oct 2011
A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats
AIM:
To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes.…
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Journal:
Authors:
- Feigh M,
- Henriksen K,
- Andreassen KV,
- Hansen C,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
14. Jul 2011
Characterization of an Ex vivo Femoral Head Model Assessed by Markers of Bone and Cartilage Turnover
OBJECTIVE:
The pathophysiology of osteoarthritis involves the whole joint and is characterized by cartilage degradation and altered subchondral bone turnover. At present, there is a need for biological models that allow investigation of the interactions between the key cellular players in bone/cart…
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Journal:
Authors:
- Madsen SH,
- Goettrup AS,
- Thomsen G,
- Christensen ST,
- Schultz N,
- Henriksen K,
- Bay-Jensen AC,
- Karsdal MA,
Bone
15. Jun 2011
Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification
Osteoclasts degrade bone matrix by secretion of hydrochloric acid and proteases. We studied the processes involved in the degradation of the organic matrix of bone in detail and found that lysosomal acidification is involved in this process and that MMPs are capable of degrading the organic matrix i…
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Journal:
Authors:
- Henriksen K,
- Sørensen MG,
- Nielsen RH,
- Gram J,
- Schaller S,
- Dziegiel MH,
- Everts V,
- Bollerslev J,
- Karsdal MA,
Bone
11. Jun 2011
Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength
Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption.To shed light …
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Journal:
Authors:
- Henriksen K,
- Flores C,
- Thomsen JS,
- Brüel AM,
- Thudium CS,
- Neutzsky-Wulff AV,
- Langenbach GE,
- Sims N,
- Askmyr M,
- Martin TJ,
- Everts V,
- Karsdal MA,
- Richter J,
Endocrinology, Type 2-Diabetes
27. May 2011
Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy
BACKGROUND:
Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a cl…
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Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Qvist P,
- Beck-Nielsen H,
- Hansen G,
- Riis BJ,
- Perrild H,
- Svendsen OL,
- Gram J,
- Karsdal MA,
- Christiansen C,
- BALLET Trial Investigators,
Extracellular Matrix Research
16. May 2011
Post-translational modifications of the extracellular matrix are key events in cancer progression: opportunities for biochemical marker development
The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, designated neoepitopes. Neoepitopes are post-translational modifications (PTMs) of proteins and are derived by processes, such as protease cleavage, citrullination, nitrosylation, glycosylation and…
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Journal:
Authors:
- Leeming DJ,
- Bay-Jensen AC,
- Vassiliadis E,
- Larsen MR,
- Henriksen K,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
8. Apr 2011
Biochemical markers of ongoing joint damage in rheumatoid arthritis--current and future applications, limitations and opportunities
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with potentially debilitating joint inflammation, as well as altered skeletal bone metabolism and co-morbid conditions. Early diagnosis and aggressive treatment to control disease activity offers the highest likelihood of …
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Journal:
Authors:
- Karsdal MA,
- Woodworth T,
- Henriksen K,
- Maksymowych WP,
- Genant H,
- Vergnaud P,
- Christiansen C,
- Schubert T,
- Qvist P,
- Schett G,
- Platt A,
- Bay-Jensen AC,
Bone
5. Apr 2011
Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials
Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Bay-Jensen AC,
- Molloy B,
- Arnold M,
- John MR,
- Byrjalsen I,
- Azria M,
- Riis BJ,
- Qvist P,
- Christiansen C,
Oncology, Bone
3. Mar 2011
Serum N-Terminal Propeptide of Collagen Type I is Associated with the Number of Bone Metastases in Breast and Prostate Cancer and Correlates to Other Bone Related Markers
BACKGROUND:
A number of biomarkers have been proven potentially useful for their ability to indicate bone metastases (BM) in cancer patients. The aim of this study was to investigate the relative utility of a newly developed N-terminal propeptide of collagen type I (PINP) human serum assay for the …
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Journal:
Authors:
- Leeming DJ,
- Koizumi M,
- Qvist P,
- Barkholt V,
- Zhang C,
- Henriksen K,
- Byrjalsen I,
- Karsdal MA,
Bone
15. Feb 2011
Osteoclast activity and subtypes as a function of physiology and pathology--implications for future treatments of osteoporosis
Osteoclasts have traditionally been associated exclusively with catabolic functions that are a prerequisite for bone resorption. However, emerging data suggest that osteoclasts also carry out functions that are important for optimal bone formation and bone quality. Moreover, recent findings indicate…
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Journal:
Authors:
- Henriksen K,
- Bollerslev J,
- Everts V,
- Karsdal MA,
Bone
4. Nov 2010
A quantitative assay for lysosomal acidification rates in human osteoclasts
The osteoclast initiates resorption by creating a resorption lacuna. The ruffled border surrounding the lacunae arises from exocytosis of lysosomes. To dissolve the inorganic phase of the bone, the vacuolar adenosine triphosphatase, located in the ruffled border, pumps protons into the resorption la…
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Journal:
Authors:
- Jensen VK,
- Nosjean O,
- Dziegiel MH,
- Boutin JA,
- Sørensen MG,
- Karsdal MA,
- Henriksen K,
Bone, Osteoporosis
26. Oct 2010
Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption
BACKGROUND:
Bone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidifi…
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Journal:
Authors:
- Sørensen MG,
- Karsdal MA,
- Dziegiel MH,
- Boutin JA,
- Nosjean O,
- Henriksen K,
Bone
10. Oct 2010
Oral salmon calcitonin--pharmacology in osteoporosis
IMPORTANCE OF THE FIELD:
Osteoporosis is a slow progressive disease with develops over decades, and where intervention is needed for an extended number of years. This highlights the need for safe intervention possibilities, which have sustained beneficial effects post-treatment.
AREAS COVERED IN…
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Authors:
Bone, Osteoporosis
5. Oct 2010
Enzyme-linked immunosorbent serum assays (ELISAs) for rat and human N-terminal pro-peptide of collagen type I (PINP)--assessment of corresponding epitopes
OBJECTIVES:
The present study describes two newly developed N-terminal pro-peptides of collagen type I (PINP) competitive enzyme-linked immunosorbent assays (ELISAs) for the assessment of corresponding PINP epitopes in the rat- and human species.
METHODS:
Monoclonal antibodies were raised again…
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Journal:
Authors:
- Leeming DJ,
- Larsen DV,
- Zhang C,
- Hi Y,
- Veidal SS,
- Nielsen RH,
- Henriksen K,
- Zheng Q,
- Barkholt V,
- Riis BJ,
- Byrjalsen I,
- Qvist P,
- Karsdal MA,
Bone
15. Aug 2010
Severe developmental bone phenotype in ClC-7 deficient mice
Bone development is dependent on the functionality of three essential cell types: chondrocytes, osteoclasts and osteoblasts. If any of these cell types is dysfunctional, a developmental bone phenotype can result. The bone disease osteopetrosis is caused by osteoclast dysfunction or impaired osteocla…
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Sims NA,
- Supanchart C,
- Kornak U,
- Felsenberg D,
- Poulton IJ,
- Martin TJ,
- Karsdal MA,
- Henriksen K,
Extracellular Matrix Research, Biomarker position
10. Jul 2010
Novel combinations of Post-Translational Modification (PTM) neo-epitopes provide tissue-specific biochemical markers--are they the cause or the consequence of the disease?
The aim of this review is to discuss the potential usefulness of novel advances in the class of biochemical markers, neo-epitopes. Neo-epitopes are post-translational modifications (PTMs) of proteins formed by processes such as protease cleavage, citrullination, nitrosylation, glycosylation and isom…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Leeming DJ,
- Woodworth T,
- Vassiliadis E,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
17. Jun 2010
Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis--the effect of sex, Kellgren-Lawrence (KL) score, body mass index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation
BACKGROUND:
Osteoarthritis (OA) involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL) score, Body Mass In…
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Journal:
Authors:
Bone, Osteoporosis
1. Jun 2010
Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption--implications for osteoclast quality
BACKGROUND:
Normal osteoclasts resorb bone by secretion of acid and proteases. Recent studies of patients with loss of function mutations affecting either of these processes have indicated a divergence in osteoclastic phenotypes. These difference in osteoclast phenotypes may directly or indirectly …
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Sørensen MG,
- Kocijancic D,
- Leeming DJ,
- Dziegiel MH,
- Karsdal MA,
- Henriksen K,
Bone
15. May 2010
Should biochemical markers of bone turnover be considered standard practice for safety pharmacology
The success in biomedical sciences such as genomics and proteomics is not paralleled in the medical product development methods. The consequence of this is a lack of translation into improved drug safety and efficacy. Therefore the US Food and Drug Administration (FDA) introduced the Critical Path I…
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Journal:
Authors:
- Henriksen K,
- Bohren KM,
- Bay-Jensen AC,
- Karsdal MA,
Rheumatology, Osteoarthritis
28. Feb 2010
Which elements are involved in reversible and irreversible cartilage degradation in osteoarthritis?
Osteoarthritis (OA) is a disease of the entire joint. Different treatment strategies for OA have been proposed and tested clinically without the desired efficacy. One reason for the scarcity of current chondroprotective agents may be the insufficient understanding of the patho-physiology of the join…
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Journal:
Authors:
- Bay-Jensen AC,
- Hoegh-Madsen S,
- Dam E,
- Henriksen K,
- Sondergaard BC,
- Pastoureau P,
- Qvist P,
- Karsdal MA,
Bone
18. Feb 2010
The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study
BACKGROUND:
The aim of this study was to investigate the pharmacokinetic and pharmacodynamic parameters of oral salmon calcitonin (oSCT) administered over 14 days to men and women presenting with osteoarthritis (OA).
MATERIALS AND METHODS:
The study was a phase-I, 2-week, placebo-controlled, do…
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Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Henriksen K,
- Riis BJ,
- Lau EM,
- Arnold M,
- Christiansen C,
Bone
16. Jan 2010
Investigations of inter- and intraindividual relationships between exposure to oral salmon calcitonin and a surrogate marker of pharmacodynamic efficacy
AIMS:
The aims of the study were to investigate interindividual variations in the bioavailability of salmon calcitonin (sCT) following single oral 0.8 mg doses at three different times of the day, and intraindividual variation in sCT bioavailability at each end of a 14-day treatment period. We also…
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Authors:
Bone, Osteoporosis
20. Sep 2009
Is bone quality associated with collagen age?
The World Health Organization defines osteoporosis as a systemic disease characterized by decreased bone tissue mass and microarchitectural deterioration, resulting in increased fracture risk. Since this statement, a significant amount of data has been generated showing that these two factors do not…
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Journal:
Authors:
- Leeming DJ,
- Henriksen K,
- Byrjalsen I,
- Qvist P,
- Madsen SH,
- Garnero P,
- Karsdal MA,
Endocrinology, Type 2-Diabetes
15. Aug 2009
A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats
Agonists of Perioxisome Proliferator-Activator Receptor gamma (PPARgamma), which work as insulin sensitizers, are approved for type 2 diabetes. However, adverse effects, such as oedemas, infarctions, and increased fracture rates, limit their applicability. We performed a head-to-head comparison of e…
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Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Nielsen RH,
- Madsen AN,
- Larsen LK,
- Christiansen C,
- Beck-Nielsen H,
- Karsdal MA,
Bone
4. Jun 2009
Local communication on and within bone controls bone remodeling
Bone remodeling is required for healthy calcium homeostasis and for repair of damage occurring with stress and age. Osteoclasts resorb bone and osteoblasts form bone. These processes normally occur in a tightly regulated sequence of events, where the amount of formed bone equals the amount of resorb…
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Journal:
Authors:
- Henriksen K,
- Neutzsky-Wulff AV,
- Bonewald LF,
- Karsdal MA,
Extracellular Matrix Research
14. May 2009
Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development
The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of prote…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Leeming DJ,
- Mitchell P,
- Duffin K,
- Barascuk N,
- Klickstein L,
- Aggarwal P,
- Nemirovskiy O,
- Byrjalsen I,
- Qvist P,
- Bay-Jensen AC,
- Dam EB,
- Madsen SH,
- Christiansen C,
Bone
2. Feb 2009
A pharmacokinetic and pharmacodynamic comparison of synthetic and recombinant oral salmon calcitonin
The aim of this study was to assess the bioavailability and pharmacodynamic efficacy of synthetic salmon calcitonin (ssCT) and recombinant salmon calcitonin (rsCT) in healthy postmenopausal women. The study was a single-blind, randomized study. Participants were 36 postmenopausal women 62 to 74 year…
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Journal:
Authors:
Bone
23. Jan 2009
Characterization of acid flux in osteoclasts from patients harboring a G215R mutation in ClC-7
The chloride-proton antiporter ClC-7 has been speculated to be involved in acidification of the lysosomes and the resorption lacunae in osteoclasts; however, neither direct measurements of chloride transport nor acidification have been performed. Human osteoclasts harboring a dominant negative mutat…
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Journal:
Authors:
- Henriksen K,
- Gram J,
- Neutzsky-Wulff AV,
- Jensen VK,
- Dziegiel MH,
- Bollerslev J,
- Karsdal MA,
Bone
12. Jan 2009
Advances in osteoclast biology resulting from the study of osteopetrotic mutations
Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast p…
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Journal:
Authors:
- Segovia-Silvestre T,
- Neutzsky-Wulff AV,
- Sorensen MG,
- Christiansen C,
- Bollerslev J,
- Karsdal MA,
- Henriksen K,
Bone
4. Sep 2008
Ion transporters involved in acidification of the resorption lacuna in osteoclasts
Osteoclasts possess a large amount of ion transporters, which participate in bone resorption; of these, the vacuolar-adenosine trisphosphatase (V-ATPase) and the chloride-proton antiporter ClC-7 acidify the resorption lacuna. However, whether other ion transporters participate in this process is cur…
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Journal:
Authors:
- Henriksen K,
- Sørensen MG,
- Jensen VK,
- Dziegiel MH,
- Nosjean O,
- Karsdal MA,
Rheumatology, Osteoarthritis
16. Jun 2008
Should subchondral bone turnover be targeted when treating osteoarthritis?
OBJECTIVE:
Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This re…
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Journal:
Authors:
- Karsdal MA,
- Leeming DJ,
- Dam EB,
- Henriksen K,
- Alexandersen P,
- Pastoureau P,
- Altman RD,
- Christiansen C,
Bone
3. Jun 2008
Characterization of the bone phenotype in ClC-7-deficient mice
Mice deficient in the chloride channel ClC-7, which is likely involved in acidification of the resorption lacuna, display severe osteopetrosis. To fully characterize the osteopetrotic phenotype, the phenotypes of osteoclasts and osteoblasts were evaluated. ClC-7(-/-) mice and their corresponding wil…
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis
8. May 2008
Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity
INTRODUCTION:
Physiological and pathophysiological cartilage turnover may coexist in articular cartilage. The distinct enzymatic processes leading to irreversible cartilage damage, compared with those needed for continuous self-repair and regeneration, remain to be identified. We investigated the c…
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Journal:
Authors:
- Karsdal MA,
- Madsen SH,
- Christiansen C,
- Henriksen K,
- Fosang AJ,
- Sondergaard BC,
Bone
22. Mar 2008
Calcitonin: a drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality
Postmenopausal osteoporosis results from a continuous imbalance between bone resorption and bone formation, favoring bone resorption. An increasing number of treatments for osteoporosis are in development and on the market. A range of differences and similarities are found between these treatment op…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Arnold M,
- Christiansen C,
Bone
22. Oct 2007
Diphyllin, a novel and naturally potent V-ATPase inhibitor, abrogates acidification of the osteoclastic resorption lacunae and bone resorption
Dissolution of the inorganic phase of bone by the osteoclasts mediated by V-ATPase and ClC-7 is a prerequisite for bone resorption. Inhibitors of osteoclastic V-ATPase or ClC-7 are novel approaches for inhibition of osteoclastic bone resorption. By testing natural compounds in acidification assays, …
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Neutzsky-Wulff AV,
- Dziegiel MH,
- Karsdal MA,
Bone
7. Sep 2007
Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival
Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased osteo…
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Journal:
Authors:
- Nielsen RH,
- Karsdal MA,
- Sørensen MG,
- Dziegiel MH,
- Henriksen K,
Bone
18. Jun 2007
Osteoclasts prefer aged bone
We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of age…
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Journal:
Authors:
- Henriksen K,
- Leeming DJ,
- Byrjalsen I,
- Nielsen RH,
- Sorensen MG,
- Dziegiel MH,
- Martin TJ,
- Christiansen C,
- Qvist P,
- Karsdal MA,
Bone
18. May 2007
Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases
Numerous experimental and clinical observations suggest that overall changes in bone resorption during menopause or treatment with hormone replacement therapy (HRT) are combined effects of changes in osteoclast number and function. Moreover, due to a coupling between osteoclastic bone resorption and…
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Journal:
Authors:
- Henriksen K,
- Tankó LB,
- Qvist P,
- Delmas PD,
- Christiansen C,
- Karsdal MA,
Bone
15. May 2007
Characterization of osteoclasts derived from CD14+ monocytes isolated from peripheral blood
Bone resorption is solely mediated by osteoclasts. Therefore, a pure osteoclast population is of high interest for the investigation of biological aspects of the osteoclasts, such as the direct effect of growth factors and hormones, as well as for testing and characterizing inhibitors of bone resorp…
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Schaller S,
- Henriksen DB,
- Nielsen FC,
- Dziegiel MH,
- Karsdal MA,
Bone
12. May 2007
Biochemical markers in preclinical models of osteoporosis
Although several treatments for osteoporosis exist, further understanding of the mode of action of current treatments, as well as development of novel treatments, are of interest. Thus, preclinical models of osteoporosis are very useful, as they provide the possibility for gaining knowledge about th…
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Schaller S,
- Karsdal MA,
Bone
22. Apr 2007
Are nonresorbing osteoclasts sources of bone anabolic activity?
Some osteopetrotic mutations lead to low resorption, increased numbers of osteoclasts, and increased bone formation, whereas other osteopetrotic mutations lead to low resorption, low numbers of osteoclasts, and decreased bone formation. Elaborating on these findings, we discuss the possibility that …
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Journal:
Authors:
- Karsdal MA,
- Martin TJ,
- Bollerslev J,
- Christiansen C,
- Henriksen K,
Bone
25. Aug 2006
Estrogen directly attenuates human osteoclastogenesis, but has no effect on resorption by mature osteoclasts
Estrogen deficiency arising with the menopause promotes marked acceleration of bone resorption, which can be restored by hormone replacement therapy. The inhibitory effects of estrogen seem to involve indirect cytokine- mediated effects via supporting bone marrow cells, but direct estrogen-receptor …
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Authors:
- Sørensen MG,
- Henriksen K,
- Dziegiel MH,
- Tankó LB,
- Karsdal MA,
Rheumatology, Osteoarthritis
14. Aug 2006
Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes
OBJECTIVE:
Calcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes …
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Journal:
Authors:
- Sondergaard BC,
- Wulf H,
- Henriksen K,
- Schaller S,
- Oestergaard S,
- Qvist P,
- Tankó LB,
- Bagger YZ,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
3. Aug 2006
Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation
OBJECTIVE:
To investigate how the time of initiation influences the effects of estrogen therapy on type II collagen (CII) turnover and the structural integrity of articular cartilage in ovariectomized rats and to determine whether estrogen exerts direct effects on the catabolic function of chondroc…
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Journal:
Authors:
- Oestergaard S,
- Sondergaard BC,
- Hoegh-Andersen P,
- Henriksen K,
- Qvist P,
- Christiansen C,
- Tankó LB,
- Karsdal MA,
Oncology, Bone
15. Jul 2006
Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion
We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (alphaalphaCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localiz…
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Authors:
- Leeming DJ,
- Delling G,
- Koizumi M,
- Henriksen K,
- Karsdal MA,
- Li B,
- Qvist P,
- Tankó LB,
- Byrjalsen I,
Rheumatology, Osteoarthritis
14. Jul 2006
Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA?
OBJECTIVE:
Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. Recent observations suggest that calcitonin may act on both osteoclasts and chondrocytes. The present review was sought to summarize eme…
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Journal:
Authors:
- Karsdal MA,
- Tankó LB,
- Riis BJ,
- Sondergaard BC,
- Henriksen K,
- Altman RD,
- Qvist P,
- Christiansen C,
Rheumatology, Osteoarthritis
23. Mar 2006
Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation
OBJECTIVE:
Both matrix metalloprotease (MMP) activity and cathepsin K (CK) activity have been implicated in cartilage turnover. We investigated the relative contribution of MMP activity and CK activity in cartilage degradation using ex vivo and in vivo models.
METHODS:
Bovine articular cartilag…
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Journal:
Authors:
- Søndergaard BC,
- Henriksen K,
- Wulf H,
- Oestergaard S,
- Schurigt U,
- Bräuer R,
- Danielsen I,
- Christiansen C,
- Qvist P,
- Karsdal MA,
Bone
5. Nov 2005
Osteoclasts from patients with autosomal dominant osteopetrosis type I caused by a T253I mutation in low-density lipoprotein receptor-related protein 5 are normal in vitro, but have decreased resorption capacity in vivo
Autosomal dominant osteopetrosis type I (ADOI) is presumably caused by gain-of-function mutations in the LRP5 gene. Patients with a T253I mutation in LRP5 have a high bone mass phenotype, characterized by increased mineralizing surface index but abnormally low numbers of small osteoclasts. To invest…
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Journal:
Authors:
- Henriksen K,
- Gram J,
- Høegh-Andersen P,
- Jemtland R,
- Ueland T,
- Dziegiel MH,
- Schaller S,
- Bollerslev J,
- Karsdal MA,
Bone
18. Oct 2005
The role of chloride channels in osteoclasts: ClC-7 as a target for osteoporosis treatment
Chloride ions play a major role in osteoclast biology and bone homeostasis. In addition to its general cellular roles, chloride is involved in the specific bone resorption activity of osteoclasts. The chloride channel ClC-7 has been shown to be mandatory for bone resorption. It is necessary for the …
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Journal:
Authors:
- Schaller S,
- Henriksen K,
- Sørensen MG,
- Karsdal MA,
Bone
2. Jun 2005
In vitro, ex vivo, and in vivo methodological approaches for studying therapeutic targets of osteoporosis and degenerative joint diseases: how biomarkers can assist
Although our approach to the clinical management of osteoporosis (OP) and degenerative joint diseases (DJD)-major causes of disability and morbidity in the elderly-has greatly advanced in the past decades, curative treatments that could bring ultimate solutions have yet to be found or developed. Eff…
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Journal:
Authors:
- Schaller S,
- Henriksen K,
- Hoegh-Andersen P,
- Søndergaard BC,
- Sumer EU,
- Tankó LB,
- Qvist P,
- Karsdal MA,
Bone
5. Feb 2005
Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption
Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhibit…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Sørensen MG,
- Gram J,
- Schaller S,
- Dziegiel MH,
- Heegaard AM,
- Christophersen P,
- Martin TJ,
- Christiansen C,
- Bollerslev J,
Bone
16. May 2004
Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II
Autosomal dominant osteopetrosis II (ADOII) is a relatively benign disorder caused by a missense mutation in the ClCN7 gene. In this study, we characterize the osteoclasts from patients with ADOII, caused by a G215R mutation, and investigate the effect on osteoclast function in vitro. Osteoclasts fr…
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Journal:
Authors:
- Henriksen K,
- Gram J,
- Schaller S,
- Dahl BH,
- Dziegiel MH,
- Bollerslev J,
- Karsdal MA,
Bone
1. Mar 2004
The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation
Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone formati…
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Journal:
Authors:
- Schaller S,
- Henriksen K,
- Sveigaard C,
- Heegaard AM,
- Hélix N,
- Stahlhut M,
- Ovejero MC,
- Johansen JV,
- Solberg H,
- Andersen TL,
- Hougaard D,
- Berryman M,
- Shiødt CB,
- Sørensen BH,
- Lichtenberg J,
- Christophersen P,
- Foged NT,
- Delaissé JM,
- Engsig MT,,
- Karsdal MA,
Bone
23. Sep 2003
RANKL and vascular endothelial growth factor (VEGF) induce osteoclast chemotaxis through an ERK1/2-dependent mechanism
Development of bone depends on a continuous supply of bone-degrading osteoclasts. Although several factors such as the matrix metalloproteinases and the integrins have been shown to be important for osteoclast recruitment, the mechanism of action remains poorly understood. In this study we investiga…
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Journal:
Authors:
- Henriksen K,
- Karsdal MA,
- Delaisse JM,
- Engsig MT,
Bone
20. Aug 2003
Transforming growth factor-beta controls human osteoclastogenesis through the p38 MAPK and regulation of RANK expression
Although RANK-L is essential for osteoclast formation, factors such as transforming growth factor-beta (TGF-beta) are potent modulators of osteoclastogenic stimuli. To systematically investigate the role of TGF-beta in human osteoclastogenesis, monocytes were isolated from peripheral blood by three …
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Journal:
Authors:
- Karsdal MA,
- Hjorth P,
- Henriksen K,
- Kirkegaard T,
- Nielsen KL,
- Lou H,
- Delaissé JM,
- Foged NT,