| First Author | Goettsch C | Year | 2013 |
| Journal | J Clin Invest | Volume | 123 |
| Issue | 11 | Pages | 4731-8 |
| PubMed ID | 24216508 | Mgi Jnum | J:205124 |
| Mgi Id | MGI:5544132 | Doi | 10.1172/JCI67603 |
| Citation | Goettsch C, et al. (2013) NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis. J Clin Invest 123(11):4731-8 |
| abstractText | ROS are implicated in bone diseases. NADPH oxidase 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 NFATc1 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 osteoclast 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. |
