Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis

Chan, B.Y., Fuller, E.S., Russell, A.K., Smith, S.M., Smith, M.M., Jackson, M.T., Cake, M.A.ORCID: 0000-0002-0072-9024, Read, R.A., Bateman, J.F., Sambrook, P.N. and Little, C.B. (2011) Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis. Osteoarthritis and Cartilage, 19 (7). pp. 874-885.

Abstract

Objectives: To investigate the regulation of sclerostin (SOST) in osteoarthritis (OA) and its potential effects on articular cartilage degradation. Methods: SOST and other Wnt-β-catenin components were immuno-localised in osteochondral sections of surgically-induced OA in knees of sheep and mice, and human OA samples obtained at arthroplasty. Regulation of SOST mRNA and protein expression by ovine chondrocytes in response to interleukin-1α (IL-1α) or tumour necrosis factor-α (TNFα) was examined in explant cultures. The effect of 25 or 250. ng/ml recombinant SOST alone or in combination with IL-1α, on ovine articular cartilage explant aggrecan degradation, and chondrocyte gene expression of Wnt-β-catenin pathway proteins, metalloproteinases and their inhibitors, and cartilage matrix proteins was quantified. Results: Contrary to being an osteocyte-specific protein, SOST was expressed by articular chondrocytes, and mRNA levels were upregulated in vitro by IL-1α but not TNFα. Chondrocyte SOST staining was significantly increased only in the focal area of cartilage damage in surgically-induced OA in sheep and mice, as well as end-stage human OA. In contrast, osteocyte SOST was focally decreased in the subchondral bone in sheep OA in association with bone sclerosis. SOST was biologically active in chondrocytes, inhibiting Wnt-β-catenin signalling and catabolic metalloproteinase [matrix metalloproteinases (MMP) and distintegrin and metalloproteinase with thrombospndin repeats (ADAMTS)] expression, but also decreasing mRNA levels of aggrecan, collagen II and tissue inhibitors of metalloproteinaes (TIMPs). Despite this mixed effect, SOST dose-dependently inhibited IL-1α-stimulated cartilage aggrecanolysis in vitro. Conclusions: These results implicate SOST in regulating the OA disease processes, but suggest opposing effects by promoting disease-associated subchondral bone sclerosis while inhibiting degradation of cartilage.

Item Type:	Journal Article
Murdoch Affiliation(s):	School of Veterinary and Biomedical Sciences
Publisher:	W. B. Saunders Co., Ltd.
Copyright:	© 2011 Osteoarthritis Research Society International.
URI:	http://researchrepository.murdoch.edu.au/id/eprint/4837

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