Role of HSP90 alpha in osteoclast formation and osteoporosis development

Osteoporosis (OP) is a systemic metabolic bone disease that occurs most frequently in the elderly. The main pathogenesis of OP is excessive proliferation and differentiation of osteoclasts, in which the peroxisome proliferator-activated receptor gamma (PPAR gamma) pathway has a pivotal role. Recently, heat shock protein (HSP)90 alpha has been identified as an important molecular chaperone with PPAR gamma, which regulates the effect of the PPAR gamma pathway. The aim of the present study was to investigate the role of HSP90 alpha involved in the regulation of osteoclast formation and the process of osteoporosis. Firstly, the expression of HSP90 alpha in osteoclast differentiation was detected by western blotting in vitro, then the effect of HSP90 alpha inhibition on the formation and differentiation of osteoclasts was examined. Furthermore, the nuclear import of PPAR gamma was also assessed to confirm the synergistic effect of HSP90 alpha. Finally, the inhibitory effect of HSP90 alpha in vivo was explored, using a mouse model of osteoporosis. As a result, in the process of osteoclast differentiation and proliferation, the expression of HSP90 alpha was upregulated. Inhibition of HSP90 alpha could block the formation and differentiation of osteoclasts, and remit osteoporosis in mice. Regarding the underlying mechanism, inhibition of HSP90 alpha could block the nuclear import of PPAR gamma to inhibit osteoclast differentiation and proliferation. In conclusion, these data indicated that the inhibition of HSP90 alpha could block osteoclast formation and remit osteoporosis by reducing the nuclear import of PPAR gamma.