Paeoniflorin regulates osteoclastogenesis and osteoblastogenesis via manipulating NF-κB signaling pathway both in vitro and in vivo

The metabolic balance between synthesis and resorption of the bone is maintained by osteoblasts and osteoclasts, respectively. Identification of agents that stimulate bone formation and suppress excessive osteoclast formation, may aid in preventing and treating conditions like osteoporosis and periprosthetic loosening. Paeoniflorin is a natural product derived from Paeonia lactiflora Pall with anti-inflammatory, analgesic, and diuretic properties. However, the effect of paeoniflorin on osteoclastogenesis and osteoblastogenesis is unknown. Herein, we demonstrated that paeoniflorin has a dose-dependent suppressive action on RANKL-evoked osteoclast differentiation and bone resorption, achieved by inhibiting the NF-κB pathway and subunit p65 nuclear translocation. Simultaneously, paeoniflorin was also found to stimulate osteoblast differentiation and bone mineralization, in addition to rescuing TNFα-impaired osteoblastogenesis. At the molecular level, paeoniflorin was found to inhibit NF-κB transcriptional activity and stimulate osteoblastogenesis-related marker gene expression (ALP, osteocalcin, OPN and Runx2), a trend that was inhibited by p65 overexpression. In ovariectomized mice, paeoniflorin was found to improve osteoblast activity, inhibit osteoclast activity, and thus, reduce ovariectomy-induced osteoporosis. Our study demonstrated that paeoniflorin simultaneously suppressed osteoclastogenesis and facilitated osteoblastogenesis by manipulating the actions of NF-κB. Therefore, paeoniflorin may serve as an ideal therapeutic antidote for osteoporosis.