Suppression of MMP activity in bovine cartilage explants cultures has little if any effect on the release of aggrecanase-derived aggrecan fragments
Progressive loss of articular cartilage is a central hallmark in many joint disease, however, the relative importance of individual proteolytic pathways leading to cartilage erosion is at present unknown. We therefore investigated the time-dependant release ex vivo of MMP- and aggrecanase-derived fr…
Journal:
Authors:
- Wang B,
- Chen P,
- Jensen AC,
- Karsdal MA,
- Madsen SH,
- Sondergaard BC,
- Zheng Q,
- Qvist P,
PLCL1 rs7595412 variation is not associated with hip bone size variation in postmenopausal Danish women
BACKGROUND:
Bone size (BS) variation is under strong genetic control and plays an important role in determining bone strength and fracture risk. Recently, a genome-wide association study identified polymorphisms associated with hip BS variation in the PLCL1 (phospholipase c-like 1) locus. Carriers …
Journal:
Authors:
- Cauchi S,
- Byrjalsen I,
- Durand E,
- Karsdal MA,
- Froguel P,
Long-term prevention with hormone-replacement therapy after the menopause: which women should be targeted?
For decades, hormone-replacement therapy (HRT) was considered safe and was the first choice in prevention of postmenopausal osteoporosis induced by estrogen deficiency. Numerous experimental and epidemiological studies further supported a protective effect of exogenous female sex hormones on atherog…
Journal:
Authors:
- Alexandersen P,
- Karsdal MA,
- Christiansen C,
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…
Journal:
Authors:
- Leeming DJ,
- Henriksen K,
- Byrjalsen I,
- Qvist P,
- Madsen SH,
- Garnero P,
- Karsdal MA,
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…
Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Nielsen RH,
- Madsen AN,
- Larsen LK,
- Christiansen C,
- Beck-Nielsen H,
- Karsdal MA,
Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers
INTRODUCTION:
At present, no disease-modifying osteoarthritis drugs (DMOADS) are approved by the FDA (US Food and Drug Administration); possibly partly due to inadequate trial design since efficacy demonstration requires disease progression in the placebo group. We investigated whether combinations…
Journal:
Authors:
- Dam EB,
- Loog M,
- Christiansen C,
- Byrjalsen I,
- Folkesson J,
- Nielsen M,
- Qazi AA,
- Pettersen PC,
- Garnero P,
- Karsdal MA,
Low-dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene
The aim of this study was to investigate whether transdermal low-dose estradiol treatment induces changes in mammographic density or heterogeneity compared with raloxifene, whether if these changes relate to changes in bone formation/resorption markers, and whether these findings indicate elevation …
Journal:
Authors:
- Nielsen M,
- Raundahl J,
- Pettersen PC,
- Loog M,
- Karemore G,
- Karsdal MA,
- Christiansen C,
Cartilage formation measured by a novel PIINP assay suggests that IGF-I does not stimulate but maintains cartilage formation ex vivo
OBJECTIVES:
The aim of this study was to investigate the time-dependent effect of insulin-like growth factor-I (IGF)-I on cartilage, evaluated by a novel procollagen type II N-terminal propeptide (PIINP) formation assay. This was performed in a cartilage model.
METHODS:
Bovine articular cartila…
Journal:
Authors:
- Madsen SH,
- Sondergaard BC,
- Bay-Jensen AC,
- Karsdal MA,
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…
Journal:
Authors:
- Henriksen K,
- Neutzsky-Wulff AV,
- Bonewald LF,
- Karsdal MA,
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…
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,
Influence of food intake on the bioavailability and efficacy of oral calcitonin
AIMS:
To investigate the influence of food intake on the bioavailability and pharmacodynamic effects of salmon calcitonin (sCT).
METHODS:
A single-blind, randomized, partly placebo-controlled study was conducted in 36 healthy postmenopausal female volunteers aged 62-74 years. The influence of f…
Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Azria M,
- Arnold M,
- Choi L,
- Riis BJ,
- Christiansen C,
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…
Journal:
Authors:
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…
Journal:
Authors:
- Henriksen K,
- Gram J,
- Neutzsky-Wulff AV,
- Jensen VK,
- Dziegiel MH,
- Bollerslev J,
- Karsdal MA,
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…
Journal:
Authors:
- Segovia-Silvestre T,
- Neutzsky-Wulff AV,
- Sorensen MG,
- Christiansen C,
- Bollerslev J,
- Karsdal MA,
- Henriksen K,