Catalog Home Page

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., 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.

[img]
Preview
PDF - Authors' Version
Download (1353kB) | Preview
    Link to Published Version: http://dx.doi.org/10.1016/j.joca.2011.04.014
    *Subscription may be required

    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.

    Publication Type: Journal Article
    Murdoch Affiliation: 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
    Item Control Page

    Downloads

    Downloads per month over past year