The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice
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...
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doaj-f9d19aa8b3a249ad984b0dda67822d0f2020-11-25T04:08:30ZengBMCCell Communication and Signaling1478-811X2019-10-0117112110.1186/s12964-019-0442-3The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in miceXiang Li0Lei Ning1Jianjun Ma2Ziang Xie3Xiangde Zhao4Gangliang Wang5Xinyu Wan6Pengcheng Qiu7Teng Yao8Haoming Wang9Shunwu Fan10Shuanglin Wan11Department of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineFirst Clinical Medical College, Wenzhou Medical UniversityDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineThe Third Hospital of Hebei Medical UniversityDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineDepartment of Orthopaedic Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of MedicineAbstract 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.http://link.springer.com/article/10.1186/s12964-019-0442-3OsteoclastsT007Peroxisome proliferator-activated receptor-gammaOsteoporosisReceptor activator of nuclear factor-κB ligand |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Xiang Li Lei Ning Jianjun Ma Ziang Xie Xiangde Zhao Gangliang Wang Xinyu Wan Pengcheng Qiu Teng Yao Haoming Wang Shunwu Fan Shuanglin Wan |
spellingShingle |
Xiang Li Lei Ning Jianjun Ma Ziang Xie Xiangde Zhao Gangliang Wang Xinyu Wan Pengcheng Qiu Teng Yao Haoming Wang Shunwu Fan Shuanglin Wan The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice Cell Communication and Signaling Osteoclasts T007 Peroxisome proliferator-activated receptor-gamma Osteoporosis Receptor activator of nuclear factor-κB ligand |
author_facet |
Xiang Li Lei Ning Jianjun Ma Ziang Xie Xiangde Zhao Gangliang Wang Xinyu Wan Pengcheng Qiu Teng Yao Haoming Wang Shunwu Fan Shuanglin Wan |
author_sort |
Xiang Li |
title |
The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice |
title_short |
The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice |
title_full |
The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice |
title_fullStr |
The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice |
title_full_unstemmed |
The PPAR-γ antagonist T007 inhibits RANKL-induced osteoclastogenesis and counteracts OVX-induced bone loss in mice |
title_sort |
ppar-γ antagonist t007 inhibits rankl-induced osteoclastogenesis and counteracts ovx-induced bone loss in mice |
publisher |
BMC |
series |
Cell Communication and Signaling |
issn |
1478-811X |
publishDate |
2019-10-01 |
description |
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. |
topic |
Osteoclasts T007 Peroxisome proliferator-activated receptor-gamma Osteoporosis Receptor activator of nuclear factor-κB ligand |
url |
http://link.springer.com/article/10.1186/s12964-019-0442-3 |
work_keys_str_mv |
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