Bone Abstracts

Objective: Wnt/β-catenin pathway is a main regulator of bone remodeling, but might be inhibited in cartilage in osteoarthritis (OA). We here investigated the effect of mechanical loading in Wnt activation and the expression of Wnt antagonists in the joint tissues.

Methods: Topgal mice were used. Mice underwent partial meniscectomy (Mnx) and sacrificed at 4, 6, and 9 weeks. Dissected knees were scanned by microCT and then prepared for cryosectioning to quantify Wnt activity by X-gal staining and the expression of Wnt antagonists such as Dkk-1, sclerostin, and sFRP-3.

Results: At baseline, Wnt activation was mainly located in osteocytes in subchondral bone and mostly absent in articular cartilage. In subchondral bone, osteocytes displayed a decrease in Wnt activity at week 4 (Mnx/sham knees compared to baseline: 0.50±0.08, P=0.034), and then an increase at weeks 6 and 9 (1.63±0.43, P=0.004 and 2.33±0.82, P=0.009 respectively). This activity paralleled the changes in BV/TV. Wnt activity was found also in the endocortical surface of growing osteophytes and in the perichondrium. The activation of Wnt was low in articular chondrocytes during the development of OA, but increased in focal cartilage lesions. In late stages, Wnt activation remained predominant in subchondral bone, osteophytes and synovium of Mnx-knees. Moreover, the expression of Dkk-1 markedly decreased in chondrocytes of the superficial layers of cartilage after partial meniscectomy compared to the sham-operated mice in which Dkk-1 was highly expressed. Sclerostin and sFRP-3 were expressed only in calcified cartilage and increased with the loss of cartilage in OA.

Conclusion: The canonical Wnt signaling pathway is mainly activated in the surrounding tissues in particular in subchondral bone and osteophytes. Therefore, modulators of Wnt activity might have different impact in joint tissues in OA.