Abstract
Introduction: Osteoarthritis (OA) is a common disease that affects 80% of the population over the age of 65 years. Little is known about the pathogenesis of OA. It is characterised by degradation of articular cartilage. Proteomic studies undertaken at our Institute using 2D gel electrophoresis and mass spectrometry identified about 30 proteins secreted by articular cartilage. Two whose synthesis was upregulated in OA were collagen II and activin A. This study quantified activin A production by human cartilage and investigated factors that may stimulate this.
Methods: Cartilage from normal (n=4) and OA (n=8) specimens were obtained from patients undergoing surgery and explants were cultured. Activin A secretion over five hours was measured in the culture medium by ELISA.
In order to determine factors that stimulate activin A production, chondrocytes were isolated from human cartilage and stimulated with various cytokines. RT-PCR methods were used to measure activin mRNA production and the culture medium was assayed for activin protein. Cartilage explants were also stimulated and activin protein levels were measured.
Results: OA cartilage produced higher amounts of activin A (range 34.9 – 97.1 ng/ml) compared to normal (range 9.4 – 15.6 ng/ml). IL-1, TGF-β and bFGF stimulated activin A mRNA and protein production by isolated chondrocytes. TGF-β and bFGF also stimulated activin production by explants, whereas IL-1 did not. This suggests that environment may determine cellular responses.
Conclusions: Activin A has not previously been described in articular cartilage. It is a homodimer of two inhibin β chains and is a member of the TGF-β superfamily originally purified from ovarian follicular fluid. Activin can induce mesenchymal cell differentiation e.g. chondrogenesis and has been shown to play a role in wound healing. To our knowledge we have shown for the first time that activin is produced by chondrocytes in response to various stimuli and that it may play a regulatory role in osteoarthritis.
Correspondence should be addressed to Mr Carlos Wigderowitz, Honorary Secretary BORS, University Dept of Orthopaedic & Trauma Surgery, Ninewells Hospital & Medical School, Dundee DD1 9SY.
