NADPH oxidase 4 limits bone mass by promoting osteoclastogenesis
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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.
Details
Original language | English |
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Pages (from-to) | 4731-4738 |
Number of pages | 8 |
Journal | Journal of Clinical Investigation |
Volume | 123 |
Issue number | 11 |
Publication status | Published - 1 Nov 2013 |
Peer-reviewed | Yes |
External IDs
ORCID | /0000-0002-8691-8423/work/164196678 |
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