Dencichine prevents ovariectomy-induced bone loss and inhibits osteoclastogenesis by inhibiting RANKL-associated NF-κB and MAPK signaling pathways

Abstract

Aims: To investigate the effect of dencichine on osteoclastogenesis in vivo and in vitro.

Methods: RANKL-induced osteoclastogenesis were treated with different concentrations of dencichine. Pit forming assays were applied to evaluate the degree of bone resorption. Osteoclastogenic markers were detected by real-time quantitative PCR (RT-qPCR) and Western blot. Micro CT was conducted to investigate the effects of dencichine on osteoclastogenesis in ovariectomized (OVX) mice.

Results: Dencichine suppressed osteoclastogenesis through the inhibition of phosphorylation of p65, p50 (NF-κB pathway), p38, ERK and JNK (MAPKs pathway) in vitro. Furthermore, dencichine inhibited the function of osteoclasts in a dose-dependent manner. In addition, the expression levels of the nuclear factor of activated T cells 1 (NFATc1) and osteoclastogenesis markers were decreased by dencichine, including MMP-9, Cathepsin K (CTSK), Tartrate-Resistant Acid Phosphatase (TRAP), C-FOS, dendritic cell specific transmembrane protein (DC-STAMP). In vivo data proved that dencichine alleviated ovariectomy-induced bone loss and osteoclastogenesis in mice.

Conclusion: Our results demonstrate that dencichine alleviates OVX-induced bone loss in mice and inhibits RANKL-mediated osteoclastogenesis via inhibition of NF-κB and MAPK pathways in vitro, suggesting that dencichine might serve as a promising candidate for treatment of bone loss diseases, including PMOP and rheumatoid arthritis.

Keywords: Dencichine; MAPK; NF-κB; Osteoclastogenesis; Signaling pathway.