The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice

• Main Authors: Xiang Li, Lei Ning, Jianjun Ma, Ziang Xie, Xiangde Zhao, Gangliang Wang, Xinyu Wan, Pengcheng Qiu, Teng Yao, Haoming Wang, Shunwu Fan, Shuanglin Wan
• Format: Article
• Language: English
• Published: BMC 2019-10-01
• Series: Cell Communication and Signaling
• Subjects: Osteoclasts; T007; Peroxisome proliferator-activated receptor-gamma; Osteoporosis; Receptor activator of nuclear factor-κB ligand
• Online Access: http://link.springer.com/article/10.1186/s12964-019-0442-3

Abstract Background Osteoclasts are key determinant cellular components implicated in the development and progression of disorders driven by bone damage. Herein, we studied the upshot of T007, an antagonist of peroxisome proliferator-activated receptor-gamma (PPARγ), on osteoclastogenesis using cell and animal models. Results The in vitro assays revealed that T007 hindered the osteoclastogenesis caused by the treatment with the receptor activator of nuclear factor-κB ligand (RANKL) through inhibiting the levels of PPARγ in cells. The PPARγ siRNA partially reproduced the inhibitory action of T007. The opposite findings were produced after PPARγ overexpression. Furthermore, T007 prevented from bone loss in a mouse model of osteoporosis induced by ovariectomy (OVX). These findings implied that T007 is a potential efficient drug for the prophylaxis and cure of osteoclast-related disorders. Conclusions Taken together, our findings demonstrated that T007 impedes osteoclastogenesis and will be useful for the therapy of bone related diseases, essentially osteoporosis.