The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice
The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice
复制标题
PPAR-γ 拮抗剂 T007 抑制 RANKL 诱导的破骨细胞生成并抵消 OVX 诱导的小鼠骨质流失
DOI：
10.1186/s12964-019-0442-3
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发表时间：
2019-10-26
影响因子：
8.4
通讯作者：
Wan, Shuanglin
中科院分区：
文献类型：
--
作者：
Li, Xiang;Ning, Lei;Wan, Shuanglin
背景破骨细胞是与骨损伤引起的疾病的发生和进展有关的关键决定性细胞成分。在此，我们研究了T007，过氧化物酶体增殖物激活受体-γ（PPAR γ）的拮抗剂，对破骨细胞生成细胞和动物模型的结果。结果T007通过抑制细胞内过氧化物酶体增殖物激活受体γ（PPAR γ）的表达，抑制核因子κ B配体受体激活因子（RANKL）诱导的破骨细胞生成。PPARgamma siRNA部分再现了T007的抑制作用。而过氧化物酶体增殖物激活物受体γ过表达则产生相反的结果。此外，T007防止了由卵巢切除术（OVX）诱导的骨质疏松症小鼠模型中的骨丢失。这些结果表明，T007是一种潜在的有效药物，用于预防和治疗破骨细胞相关疾病。结论T007可抑制破骨细胞的生成，对骨质疏松症等骨相关疾病的治疗具有重要意义。
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 (PPAR gamma), 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-kappa B ligand (RANKL) through inhibiting the levels of PPAR gamma in cells. The PPAR gamma siRNA partially reproduced the inhibitory action of T007. The opposite findings were produced after PPAR gamma 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.