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Bone Abstracts (2014) 3 PP15 | DOI: 10.1530/boneabs.3.PP15

Arthritis and other joint diseases: translational and clinical

Bone secreted dickkopf-related protein 1 ameliorates osteoarthritis in mice

Thomas Funck-Brentano, Wafa Bouaziz, Caroline Marty, Valérie Geoffroy, Eric Hay & Martine Cohen-Solal

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


Objective: Cartilage loss and subchondral bone changes are hallmarks of osteoarthritis (OA). The Wnt family is involved in the regulation of bone and cartilage. We have shown that the Wnt/β-catenin pathway is activated in bone during OA, but the effect of its inhibition in bone in cartilage remodeling is unknown. We here investigated the impact of the bone-specific inhibition of Wnt during the development of OA.

Methods: Partial meniscectomy (Mnx) was performed in mice to promote OA. We assessed the bone and cartilage parameters in OA development using mice overexpressing Dkk1 in bone (2.3 Col1-Dkk1Tg). The effects of Dkk-1 in chondrocyte and osteoblast metabolism were further assessed using supernatant transfer and MMP expression.

Results: At baseline, Dkk1-Tg mice had lower bone volume which was further reduced in MNX knees. This was accompanied by a reduction of the subchondral bone and osteophyte volume. In WT mice, the number of Dkk1 (+) chondrocytes was high at baseline (84.2±3.1%), decreased markedly during the course of OA from week 4 (14.4±3.8%) to week 6 (5.7±1.6%). Dkk1-Tg experienced a lower OA score than WT mice (5.1±0.63 vs 8.4±0.6, P=0.002) independently of the expression of Dkk1 in chondrocytes. However, addition of supernatant of osteoblasts derived from Dkk-1-Tg mice or in vitro addition of rhDkk1 in chondrocytes promoted the chondrocytic expression of MMPs while was decreased by the supernatant of pre-exposed osteoblasts with Dkk1. Because Dkk1-Tg osteoblasts produced low VEGF, we tested whether VEGF could mediate the anti-catabolic effect observed in vivo. Blocking VEGF in the supernatant of osteoblast cultures reversed the expression of MMPs by chondrocytes.

Conclusion: Inhibition of Wnt pathway in bone cells decreased OA severity by reducing VEGF production. Targeting bone could be a useful approach for the treatment of 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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