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Bone Abstracts (2014) 3 HT4 | DOI: 10.1530/boneabs.3.HT4

INSERM U1132 and University Paris-7, Paris, France.


Purpose: Sclerostin, a Wnt inhibitor produced by osteocytes that regulate bone remodelling, might be involved in cartilage metabolism. Therefore, we assessed the effect of sclerostin in osteoarthritis using SOST-deficient mice.

Methods: SOST-KO and wild type (WT) mice underwent partial meniscectomie (Mnx). Mice were sacrificed at 4, 6 or 9 weeks after Mnx to analyze i) bone volume (BV/TV) at the femoral condyle, ii) osteophyte volume (microCT), iii) cartilage damage (OA score) and iv) expression of matrix proteins. Primary murine chondrocyte were cultured with Wnt3a and sclerostin to analyze metabolic markers (RT-qPCR, WB). Proteoglycan content and GAGs accumulation was quantified. We next investigated the role of canonical and non-canonical Wnt pathways.

Results: Sclerostin was expressed in the calcified cartilage and enhanced in OA joint. At any time, cartilage was preserved in SOST-KO mice despite a markedly high BV/TV.

Mnx induced a higher OA score in SOST-KO mice than in WT at Week 4 (6.66±0.57 vs 3.25±0.95, P<0.05) and Week 6 (11±1 vs 7±0.81, P<0.05). Osteophyte volume was not affected by the lack of sclerostin. Enhanced chondrocyte catabolism was observed with increased type X collagen and Adamts-4 expressions. In primary chondrocytes, Wnt reduced the proteoglycan release but was rescued by sclerostin. Wnt increased the expression of Adamts, MMPs and type X collagen, while this effect was totally abolished by sclerostin through the activation of the canonical pathway. Furthermore, sclerostin inhibited the Wnt-induced phosphorylation of JNK, rescued the accumulation of GAGs and the expression of the anabolic genes when JNK pathway was inhibited.

Conclusions: Lack of sclerostin increases the subchondral bone accretion and accelerates cartilage damage in OA. Sclerostin maintains the chondrocyte metabolism by inhibiting Wnt canonical and non-canonical JNK pathways. These data suggest that sclerostin contribute to cartilage integrity in OA.

Volume 3

European Calcified Tissue Society Congress 2014

Prague, Czech Republic
17 May 2014 - 20 May 2014

European Calcified Tissue Society 

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