Bone Abstracts

Purpose: Osteoclastogenesis is enhanced in osteoarthritis (OA). We have demonstrated that cartilage breakdown is reduced when osteoclastogenesis is inhibited in murine models. Wnt activity, known to regulate the bone and chondrocyte cell function, might contribute to the mechanisms that promote cartilage catabolism. Our purpose was to evaluate whether osteoclast-secreted molecules affect the chondrocyte metabolism and assess the contribution of Wnt pathway.

Methods: We used osteoclasts derived from RAW cells. Primary murine chondrocyte (Ch) were cultured in the presence of osteoclast conditioned medium (Oc-CM) for 48 h. The gene and protein expressions of catabolism and anabolism were analyzed by RT-qPCR and western blot. To investigate the regulation of canonical Wnt pathway, transactivation assay was performed in primary chondrocytes derived from Topgal mice and cultured with Oc-CM. Western blot and immunocytochemistry were used to confirm the activation of β-catenin canonical Wnt signaling pathway. Finally, in order to confirm the role of Wnt canonical signaling, the β-catenin translocation was activated by lithium chloride (LiCl) in addition of the Oc-CM.

Results: Oc-CM induced a marked decrease in proteoglycan release by chondrocytes. Oc-CM reduced the expression of anabolic genes (collagen type II, Aggrecan and Sox-9) while increased the expression of catabolic genes (MMP-3, -13, Adamts-4, -5). We then monitored the nuclear translocation of β-catenin induced by Oc-CM. We observed an abolition of the translocation of β-catenin and subsequently of Topgal activity along with the reduction of Wnt target genes (Axin, Wisp1 C-Myc). LiCl reduces the expression of catabolic genes induced by Oc-CM, indicating the involvement of the Wnt-canonical pathway on the regulation of catabolic genes.

Conclusion: We here demonstrated that osteoclasts secrete soluble factors that are able to disrupt the balance of chondrocyte metabolism via the inhibition of the Wnt canonical signaling. Therefore, our data indicate that manipulating bone may affect chondrocyte function.