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Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM–increased serum CIIM in subjects with severe radiographic osteoarthritis.

April 1, 2011

Clin Biochem

Abstract OBJECTIVES In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers. METHODS A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against the neoepitope were developed. CIIM was measured in cartilage explants in the presence or absence […]

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Oral salmon calcitonin reduces cartilage and bone pathology in an osteoarthritis rat model with increased subchondral bone turnover.

April 1, 2011

Osteoarthritis Cartilage

Abstract OBJECTIVES Traumatic osteoarthritis (OA) is possibly augmented by effects from loss of sex hormones. Salmon calcitonin is shown to reduce OA pathogenesis and bone resorption. We investigated the effects of oral salmon calcitonin treatment and ovariectomy on cartilage and bone pathology in a traumatic OA model. METHODS Six groups with 10 7-month-old female Sprague […]

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Aggrecanase- and matrix metalloproteinase-mediated aggrecan degradation is associated with different molecular characteristics of aggrecan and separated in time ex vivo.

May 1, 2010

Biomarkers

Abstract Aggrecan is one of the first proteins to be depleted from articular cartilage in early osteoarthritis. We investigated the molecular differences between matrix metalloproteinase (MMP)- and aggrecanase-mediated aggrecan degradation, as a consequence of their distinct time-dependent degradation profiles. Cartilage degradation was induced by cytokine stimulation in bovine articular cartilage explants and quantified by a […]

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Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes.

April 5, 2010

BMC Musculoskelet Disord

Abstract BACKGROUND Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteoglycans and collagen-type-II synthesis in osteoarthritic (OA) cartilage. METHODS Human OA cartilage explants were cultured with […]

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MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation–divergence in pathways leading to aggrecanase and MMP-mediated articular cartilage degradation.

March 1, 2010

Osteoarthritis Cartilage

Abstract OBJECTIVES Matrix metalloproteinases (MMPs) and aggrecanases are essential players in cartilage degradation. However, the signaling pathways that results in MMP and/or aggrecanase synthesis and activation are not well understood. We investigated the molecular events leading to MMP- and aggrecanase-mediated cartilage degradation. METHODS Cartilage degradation was induced in bovine articular cartilage explants by oncostatin M […]

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Application of biochemical markers in development of drugs for treatment of osteoarthritis.

February 1, 2010

Biomarkers

Abstract Osteoarthritis is a chronic disease for which no efficacious medical intervention is yet available. Recent disappointments in late-stage clinical development of disease-modifying osteoarthritic drugs (DMOADs) have precipitated efforts in biomarker discovery aimed at developing an analytical tool box with the potential to improve the clinical development process. In this review, we seek to provide […]

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Which elements are involved in reversible and irreversible cartilage degradation in osteoarthritis?

February 1, 2010

Rheumatol Int

Abstract 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 joint and whether the joint damage is reversible or irreversible. In […]

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The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study.

February 1, 2010

Osteoarthritis Cartilage

Abstract 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, double-blind, double-dummy, randomized, gender-stratified study including 73 subjects aged 57-75 years. Patients had […]

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Biochemical markers of joint tissue turnover.

February 1, 2010

Assay Drug Dev Technol

Abstract Recent disappointments in late stage developments of anti-osteoarthritic drugs have reinforced efforts to develop better biomarkers for application in both the drug development process as well as in the routine management of these patients. Here we provide a brief review of biochemical tests available for the study of tissue turnover in each of the […]

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Investigations of inter- and intraindividual relationships between exposure to oral salmon calcitonin and a surrogate marker of pharmacodynamic efficacy.

January 1, 2010

Eur J Clin Pharmacol

Abstract 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 investigated correlations between exposure to sCT and […]

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