Low concentration flufenamic acid enhances osteogenic differentiation of mesenchymal stem cells and suppresses bone loss by inhibition of the NF-κB signaling pathway

Stem Cell Research & Therapy

Weiliang Wu¹  Dandan Xia²  Zheng Li³  Ranli Gu³  Ping Zhang³  Xuenan Liu³  Yuan Zhu³  Siyi Wang³  Yongsheng Zhou³  Yunsong Liu³  Hao Liu³ 

[1] Department of Implantology II, The Affiliated Stomatological Hospital of Fujian Medical University;Department of Materials Science and Engineering, College of Engineering, Peking University;Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, National Clinical Research Center for Oral Diseases;

关键词: Flufenamic acid;    Mesenchymal stem cells;    Osteogenesis;    Osteoporosis;    Nuclear factor-κB;   

DOI  :  10.1186/s13287-019-1321-y

来源: DOAJ

【 摘 要 】

Abstract Background As the representative of fenamic acids, an important group of NSAIDs, flufenamic acid (FFA) has been used for anti-inflammation and analgesia in the clinic. Recently, researches have focused on the role of some members of NSAIDs in promoting osteogenesis. However, little attention has been paid to the subgroup of fenamic acids, and it remains unclear whether FFA and other fenamic acids could regulate mesenchymal stem cells’ (MSCs) lineage commitment and bone regeneration. Methods Here we treated two kinds of human MSCs with FFA at different concentrations in vitro and examined the effect of FFA on osteogenic differentiation of human MSCs. This was followed by heterotopic bone formation assay in nude mice. In addition, ovariectomized and aged mice were used as osteoporotic models to test the effect of FFA on osteoporosis. Besides, activators and inhibitor of nuclear factor-κB (NF-κB) signaling pathway and western blot were used to clarify the mechanism of the promoting effect of low concentration FFA on osteogenesis. Results Our results indicated that low concentrations of FFA could significantly enhance osteogenic differentiation of human MSCs in vitro, as well as in vivo. In addition, FFA treatment suppressed bone loss in ovariectomized and aged mice. Mechanistically, FFA at low concentrations promoted osteogenesis differentiation of human MSCs by inhibition of the NF-κB signaling pathway. Conclusions Collectively, our study suggested that low concentration FFA could be used in bone tissue engineering or osteoporosis by promoting osteogenic differentiation of human MSCs.

【 授权许可】

Unknown