期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 123, 期 11, 页码 4731-4738出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI67603
关键词
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资金
- MeDDrive33 program of the Medical Faculty of the Technical University of Dresden
- Deutsche Forschungsgemeinschaft [SFB815/TP1, SFB834/TP2, GO1801/4-1, FOR1586 HO 1875/12-1, FOR1586 HO 1875/13-1]
- Hugelschaffner-Stiftung
- DFG excellence cluster ECCPS
- BioPersMed [825329]
- Austrian Federal Ministry of Transport, Innovation and Technology (BMVIT)
- Austrian Federal Ministry of Economics and Labour/Federal Ministry of Economy, Family and Youth (BMWA/BMWFJ)
- Styrian Business Promotion Agency (SFG)
- Genkyotex Innovation SAS
ROS are implicated in bone diseases. NADPH oxid.ase 4 (NOX4), a constitutively active enzymatic source of ROS, may contribute to the development of such disorders. Therefore, we studied the role of NOX4 in bone homeostasis. Nox4(-/-) mice displayed higher bone density and reduced numbers and markers of osteoclasts. Ex vivo, differentiation of monocytes into osteoclasts with RANKL and M-CSF induced Nox4 expression. Loss of NOX4 activity attenuated osteoclastogenesis, which was accompanied by impaired activation of RANKL-induced NFATcl and c-JUN. In an in vivo model of murine ovariectomy-induced osteoporosis, pharmacological inhibition or acute genetic knockdown of Nox4 mitigated loss of trabecular bone. Human bone obtained from patients with increased osteodast activity exhibited increased NOX4 expression. Moreover, a SNP of NOX4 was associated with elevated circulating markers of bone turnover and reduced bone density in women. Thus, NOX4 is involved in bone loss and represents a potential therapeutic target for the treatment of osteoporosis.
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