Zoledronate promotes ECM degradation and apoptosis via Wnt/beta-catenin

This study examined the potential mechanism of zoledronate on interleukin (IL)-1 beta-induced temporomandibular joint osteoarthritis (TMJOA) chondrocytes, using IL-1 beta-induced rabbit immortalized mandibular condylar chondrocytes cultured with zoledronate. Cell viability, apoptosis, mRNA, and protein expression of relevant genes involved in extracellular matrix (ECM) degradation, apoptosis, and Wnt/beta-catenin signaling were examined. The involvement of the Wnt/beta-catenin signaling was examined using Wnt/beta-catenin inhibitor (2-(4-(trifluoromethyl)phenyl)-7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidin-4-ol (XAV-939)) and activator lithium chloride (LiCl). Aggrecan and type II collagen were downregulated by zoledronate, especially with 100 nM for 48 h (p < 0.01), consistently with the upregulation of A disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) (p < 0.001), matrix metalloprotease-9 (MMP-9) (p < 0.01), caspase-3 (p < 0.001) and downregulation of proliferating cell nuclear antigen (PCNA) (p < 0.01). The apoptotic rate increased from 34.1% to 45.7% with 100 nM zoledronate for 48 h (p < 0.01). The effects of zoledronate on ADAMTs4 (p < 0.001), MMP-9 (p < 0.001), caspase-3 (p < 0.001), and PCNA (p < 0.01) were reversed by XAV-939, while LiCl increased caspase-3 expression (p < 0.01). In conclusion, zoledronate enhances IL-1 beta-induced ECM degradation and cell apoptosis in TMJOA chondrocytes. Wnt/beta-catenin signaling might be involved in this process, but additional studies are necessary to determine the exact involvement of Wnt/beta-catenin signaling in chondrocytes after zoledronate treatment.