Paeoniflorin regulates osteoclastogenesis and osteoblastogenesis via manipulating NF-κB signaling pathway both in vitro and in vivo
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Yanmao Wang1,*, Jiezhi Dai1,*, Yu Zhu1, Wanrun Zhong1, Shengdi Lu1, Hua Chen1 and Yimin Chai1
1Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, PR China
*These authors contributed equally to this work
Yimin Chai, email: [email protected]
Hua Chen, email: [email protected]
Keywords: paeoniflorin; osteoclastogenesis; osteoblastogenesis; NF-κB; OVX
Received: September 07, 2017 Accepted: November 16, 2017 Published: December 27, 2017
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.
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