Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation

dc.contributor.author Mandal, Chandi C.
dc.contributor.author Ganapathy, Suthakar
dc.contributor.author Gorin, Yves
dc.contributor.author Mahadev, Kalyankar
dc.contributor.author Block, Karen
dc.contributor.author Abboud, Hanna E.
dc.contributor.author Harris, Stephen E.
dc.contributor.author Ghosh-Choudhury, Goutam
dc.contributor.author Ghosh-Choudhury, Nandini
dc.date.accessioned 2022-03-27T04:11:25Z
dc.date.available 2022-03-27T04:11:25Z
dc.date.issued 2011-01-15
dc.description.abstract BMP-2 (bone morphogenetic protein-2) promotes differentiation of osteoblast precursor cells to mature osteoblasts that form healthy bone. In the present study, we demonstrate a novel mechanism of BMP-2-induced osteoblast differentiation. The antioxidant NAC (N-acetyl-L-cysteine) and the flavoprotein enzyme NAD(P)H oxidase inhibitor DPI (diphenyleneiodonium) prevented BMP-2-stimulated alkaline phosphatase expression and mineralized bone nodule formation in mouse 2T3 pre-osteoblasts. BMP-2 elicited a rapid generation of ROS (reactive oxygen species) concomitant with increased activation of NAD(P)H oxidase. NAC andDPI inhibited BMP-2-induced ROS production and NAD(P)H oxidase activity respectively. NAD(P)H oxidases display structurally similar catalytic subunits (Nox1-5) with differential expression in various cells. We demonstrate that 2T3 pre-osteoblasts predominantly express the Nox4 isotype of NAD(P)H oxidase. To extend this finding, we tested the functional effects of Nox4. Adenovirus-mediated expression of dominant-negative Nox4 inhibited BMP-2-induced alkaline phosphatase expression. BMP-2 promotes expression of BMP-2 for maintenance of the osteoblast phenotype. NAC and DPI significantly blocked BMP-2-stimulated expression of BMP2 mRNA and protein due to a decrease in BMP2 gene transcription. Dominant-negative Nox4 also mimicked this effect of NAC and DPI. Our results provide the first evidence for a new signalling pathway linking BMP-2-stimulated Nox4-derived physiological ROS to BMP-2 expression and osteoblast differentiation. © The Authors Journal compilation © 2011 Biochemical Society.
dc.identifier.citation Biochemical Journal. v.433(2)
dc.identifier.issn 02646021
dc.identifier.uri 10.1042/BJ20100357
dc.identifier.uri https://portlandpress.com/biochemj/article/433/2/393/45173/Reactive-oxygen-species-derived-from-Nox4-mediate
dc.identifier.uri https://dspace.uohyd.ac.in/handle/1/6748
dc.subject Bone morphogenetic protein-2 (BMP-2)
dc.subject Bone morphogenetic protein-2 gene autoregulation
dc.subject Bone morphogenetic protein-2 signalling
dc.subject Osteoblast differentiation
dc.subject Reactive oxygen species
dc.title Reactive oxygen species derived from Nox4 mediate BMP2 gene transcription and osteoblast differentiation
dc.type Journal. Article
dspace.entity.type
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