Journal article
Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis
Osteoarthritis and Cartilage, Vol.19(7), pp.874-885
2011
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.
Details
- Title
- Increased chondrocyte sclerostin may protect against cartilage degradation in osteoarthritis
- Authors/Creators
- B.Y. Chan (Author/Creator) - Kolling Institute of Medical ResearchE.S. Fuller (Author/Creator) - Kolling Institute of Medical ResearchA.K. Russell (Author/Creator) - Kolling Institute of Medical ResearchS.M. Smith (Author/Creator) - Kolling Institute of Medical ResearchM.M. Smith (Author/Creator) - Kolling Institute of Medical ResearchM.T. Jackson (Author/Creator) - Kolling Institute of Medical ResearchM.A. Cake (Author/Creator) - Murdoch UniversityR.A. Read (Author/Creator) - Murdoch UniversityJ.F. Bateman (Author/Creator) - Murdoch Children's Research InstituteP.N. Sambrook (Author/Creator) - Kolling Institute of Medical ResearchC.B. Little (Author/Creator) - Kolling Institute of Medical Research
- Publication Details
- Osteoarthritis and Cartilage, Vol.19(7), pp.874-885
- Publisher
- W. B. Saunders Co., Ltd.
- Identifiers
- 991005542321507891
- Copyright
- © 2011 Osteoarthritis Research Society International.
- Murdoch Affiliation
- School of Veterinary and Biomedical Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.34 Orthopedics
- 1.34.255 Osteoarthritis
- Web Of Science research areas
- Orthopedics
- Rheumatology
- ESI research areas
- Clinical Medicine