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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Hepatic System, Alcoholic Liver Disease
13. Dec 2012
Phosphodiesterase inhibition mediates matrix metalloproteinase activity and the level of collagen degradation fragments in a liver fibrosis ex vivo rat model
BACKGROUND:
Accumulation of extracellular matrix (ECM) and increased matrix metalloproteinase (MMP) activity are hallmarks of liver fibrosis. The aim of the present study was to develop a model of liver fibrosis combining ex vivo tissue culture of livers from CCl(4) treated animals with an ELISA de…
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Authors:
- Veidal SS,
- Nielsen MJ,
- Leeming DJ,
- Karsdal MA,
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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Authors:
- Wang Y,
- Sørensen MG,
- Zheng Q,
- Zhang C,
- Karsdal MA,
- Henriksen K,
Rheumatology, Spondyloarthropathies
17. Nov 2012
Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study
Ankylosing spondylitis (AS) is characterized by gradual cementation of the vertebrae, a process that is described by excessive extracellular matrix remodeling. Specific matrix metalloproteinase (MMP)-derived collagen fragments are released to the circulation, and measurement of those might act as bi…
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Authors:
- Bay-Jensen AC,
- Leeming DJ,
- Kleyer A,
- Veidal SS,
- Schett G,
- Karsdal MA,
Bone, Osteoporosis
28. Oct 2012
Recommendations on the management of fragility fracture risk in women younger than 70 years
The risk for fragility fracture represents a problem of enormous magnitude. It is estimated that only a small fraction of women with this risk take the benefit of preventive measures. The relationship between estrogen and bone mass is well known as they are the other factors related to the risk for …
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Authors:
- Palacios S,
- Christiansen C,
- Sánchez Borrego R,
- Gambacciani M,
- Hadji P,
- Karsdal MA,
- Lambrinoudaki I,
- Lello S,
- O'Beirne B,
- Romao F,
- Rozenberg S,
- Stevenson JC,
- Ben-Rafael Z,
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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Authors:
- Neutzsky-Wulff AV,
- Andreassen KV,
- Hjuler ST,
- Feigh M,
- Bay-Jensen AC,
- Zheng Q,
- Henriksen K,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
4. Oct 2012
IL-6 receptor inhibition positively modulates bone balance in rheumatoid arthritis patients with an inadequate response to anti-tumor necrosis factor therapy: biochemical marker analysis of bone metabolism in the tocilizumab RADIATE study (NCT00106522)
OBJECTIVE:
To evaluate changes in biochemical markers of bone metabolism in response to tocilizumab in patients with anti-tumor necrosis factor-refractory rheumatoid arthritis (RA).
METHODS:
RADIATE was a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial. C-reactive pro…
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Authors:
- Karsdal MA,
- Schett G,
- Emery P,
- Harari O,
- Byrjalsen I,
- Kenwright A,
- Bay-Jensen AC,
- Platt A,
Rheumatology, Rheumatoid Arthritis
20. Sep 2012
Matrix metalloproteinase-dependent turnover of cartilage, synovial membrane, and connective tissue is elevated in rats with collagen induced arthritis
BACKGROUND:
Rheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints. The thickness of the synovial membrane increases and surrounding tissue degrades, leading to altered collagen balance in the tissues. In this study, we investigated the altered tissue bal…
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Authors:
- Siebuhr AS,
- Wang J,
- Karsdal MA,
- Bay-Jensen AC,
- Y J,
- Q Z,
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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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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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,
Respiratory System, Idiopathic Pulmonary Fibrosis, Chronic Obstructive Pulmonary Disease
20. Jul 2012
Measurement of MMP-9 and -12 degraded elastin (ELM) provides unique information on lung tissue degradation
BACKGROUND:
Elastin is an essential component of selected connective tissues that provides a unique physiological elasticity. Elastin may be considered a signature protein of lungs where matrix metalloprotease (MMP) -9-and -12, may be considered the signature proteases of the macrophages, which in …
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Authors:
- Skjøt-Arkil H,
- Clausen RE,
- Nguyen QH,
- Wang Y,
- Zheng Q,
- Martinez FJ,
- Hogaboam CM,
- Han M,
- Klickstein LB,
- Larsen MR,
- Nawrocki A,
- Leeming DJ,
- Karsdal MA,
Respiratory System, Chronic Obstructive Pulmonary Disease, Idiopathic Pulmonary Fibrosis
11. Jul 2012
Serological investigation of the collagen degradation profile of patients with chronic obstructive pulmonary disease or idiopathic pulmonary fibrosis
In both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), abnormally high collagen remodeling occurs within the lung tissue. Matrix metalloproteinase (MMP)-degraded type I, III, IV, V and VI collagen and a disintegrin and metalloproteinase with thrombospondin moti…
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Authors:
- Leeming DJ,
- Sand JM,
- Nielsen MJ,
- Genovese F,
- Martinez FJ,
- Hogaboam CM,
- Han MK,
- Klickstein LB,
- Karsdal MA,
Extracellular Matrix Research, Cardiovascular System, Acute Myocardial Infarct
6. Jul 2012
Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
BACKGROUND:
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical s…
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Authors:
- Vassiliadis E,
- Rasmussen LM,
- Byrjalsen I,
- Larsen DV,
- Chaturvedi R,
- Hosbond S,
- Saabye L,
- Diederichsen AC,
- Genovese F,
- Duffin KL,
- Zheng Q,
- Chen X,
- Leeming DJ,
- Christiansen C,
- Karsdal MA,
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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Authors:
- Chen-An P,
- Andreassen KV,
- Henriksen K,
- Karsdal MA,
- Bay-Jensen AC,
Hepatic System, Alcoholic Liver Disease
7. Jun 2012
Circulating levels of a collagen type v propeptide fragment in a carbon tetrachloride reversible model of liver fibrosis
AIM:
To measure levels of the collagen V formation marker CO5-1230 during liver fibrosis progression and regression.
METHODS:
Monoclonal antibodies were raised against the sequence TAALGDIMGH located at the start of the C-terminal propeptide between amino acid position 1230' and 1239' (CO5-1230…
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Authors:
- Vassiliadis E,
- Veidal SS,
- Hansen C,
- Karsdal MA,
- Leeming DJ,
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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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,
Hepatic System, Alcoholic Liver Disease
16. May 2012
Enzyme-linked immunosorbent serum assay specific for the 7S domain of Collagen Type IV (P4NP 7S): A marker related to the extracellular matrix remodeling during liver fibrogenesis
AIM:
The present study describes the ability of a newly developed N-terminal pro-peptides of type IV collagen 7S domain (P4NP 7S) competitive enzyme-linked immunosorbent assay (ELISA) for describing liver fibrosis. The assay applies a monoclonal antibody specific for a PIVNP 7S epitope 100% homolog…
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Authors:
- Leeming DJ,
- Nielsen MJ,
- Dai Y,
- Veidal SS,
- Vassiliadis E,
- Zhang C,
- He Y,
- Vainer B,
- Zheng Q,
- Karsdal MA,
Cardiovascular System, Atherosclerosis
10. May 2012
Novel cardiac-specific biomarkers and the cardiovascular continuum
The concept of the cardiovascular continuum, introduced during the early 1990s, created a holistic view of the chain of events connecting cardiovascular-related risk factors with the progressive development of pathological-related tissue remodelling and ultimately, heart failure and death. Understan…
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Authors:
- Vassiliadis E,
- Barascuk N,
- Didangelos A,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
7. May 2012
MMP mediated type V collagen degradation (C5M) is elevated in ankylosing spondylitis
OBJECTIVES:
Type V collagen has been demonstrated to control fibril formation. The aim of this study was to develop an ELISA capable of detecting a fragment of type V collagen generated by MMP-2/9 and to evaluate the assay as biomarker for ankylosing spondylitis (AS).
DESIGN AND METHODS:
A frag…
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Authors:
- Veidal SS,
- Larsen DV,
- Chen X,
- Sun S,
- Zheng Q,
- Bay-Jensen AC,
- Leeming DJ,
- Nawrocki A,
- Larsen MR,
- Schett G,
- 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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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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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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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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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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Authors:
- Skjøt-Arkil H,
- Barascuk N,
- Larsen L,
- Dziegiel M,
- Henriksen K,
- Karsdal MA,
Rheumatology, Osteoarthritis
18. Jan 2012
The distribution pattern of critically short telomeres in human osteoarthritic knees
INTRODUCTION
Telomere shortening is associated with a number of common age-related diseases. A role of telomere shortening in osteoarthritis (OA) has been suggested, mainly based on the assessment of mean telomere length in ex vivo expanded chondrocytes. We addressed this role directly in vivo by u…
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Authors:
- Harbo M,
- Bendix L,
- Bay-Jensen AC,
- Graakjaer J,
- Søe K,
- Andersen TL,
- Kjaersgaard-Andersen P,
- Koelvraa S,
- Delaisse JM,
Hepatic System, Extracellular Matrix Research
3. Jan 2012
Molecular serum markers of liver fibrosis
Fibrosis is a hallmark histologic event of chronic liver diseases and is characterized by the excessive accumulation and reorganization of the extracellular matrix (ECM). The gold standard for assessment of fibrosis is liver biopsy. As this procedure has various limitations, including risk of patien…
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Journal:
Authors:
- Liu T,
- Wang X,
- Karsdal MA,
- Leeming DJ,
- Genovese F,