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Aggrecan cleavage by a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 5 (ADAMTS-5) is crucial for the breakdown of cartilage matrix during osteoarthritis, a degenerative joint disease that leads to the progressive destruction of articular structures. The mechanisms of ADAMTS-5 activation and their links to the pathogenesis of osteoarthritis remain poorly understood, but syndecans have been shown to be involved in the activation of ADAMTS-4 (ref. 3). Here we show that syndecan-4 is specifically induced in type X collagen-producing chondrocytes both in human osteoarthritis and in murine models of the disease. The loss of syndecan-4 in genetically modified mice and intra-articular injections of syndecan-4-specific antibodies into wild-type mice protect from proteoglycan loss and thereby prevent osteoarthritic cartilage damage in a surgically induced model of osteoarthritis. The occurrence of less severe osteoarthritis-like cartilage destruction in both syndecan-4-deficient mice and syndecan-4-specific antibody-treated wild-type mice results from a marked decrease in ADAMTS-5 activity. Syndecan-4 controls the activation of ADAMTS-5 through direct interaction with the protease and through regulating mitogen-activated protein kinase (MAPK)-dependent synthesis of matrix metalloproteinase-3 (MMP-3). Our data suggest that strategies aimed at the inhibition of syndecan-4 will be of great value for the treatment of cartilage damage in osteoarthritis.

The aim of this study was to examine the frequency of amyloid deposition in patients with end-stage rheumatoid arthritis (RA) of the hip. The impact on the clinical situation and the RA severity regarding the inflammation was analyzed. Fifty patients with RA who consecutively underwent total hip replacement were prospectively evaluated. X-rays of the patients were analyzed radiologically (Larsen score) to quantify the radiological changes. A clinical score (Harris Hip Score) was preoperatively calculated from every patient. A laboratory set of inflammation markers (erythrocyte sedimentation rate, CRP, serum amyloid A-SAA, electrophoresis) was measured in every patient the day before the operation. Specimens of bone and cartilage from the femoral head and of the capsule were obtained from every patient intraoperatively for histological evaluation. A histological grading was performed. In patients with amyloid deposits, the subtypes were characterized immunohistologically. Ninety-two percent of the patients had raised SAA in the blood samples, but the only amyloid subtype was ATTR. No correlation was found for any other measured item, such as inflammation signs in the blood samples, the histological grading, the radiological or the clinical score. Amyloid plays a role in inflammatory joint destruction processes in RA with raised SAA values, but the amyloid deposits in the joint are of a different subtype. Thus, these amyloid deposits can be considered as minor pathologic significance. A correlation to the radiological and histological changes was ruled out by our study. As in degenerative arthritis, ATTR amyloid deposits may be an incidental finding in aged joints. [ABSTRACT FROM AUTHOR]

The article discusses a study on the frequency of structural changes in the vastus medialis muscle in patients with osteoarthritis (OA) of the knee. The research also assessed morphological changes in relation to clinical features that might have contributed to muscle injury. Atrophy of type 1 fibers was noted in 32 percent of patients included in the study. It cites the cofactors in the development of OA, such as neurogenic muscular atrophy and muscle fiber degeneration.