Nox4 promotes osteoblast differentiation through TGF-beta signal pathway

NADPH oxidase 4 (Nox4) is the main source of reactive oxygen species, which promote osteoclast formation and lead to bone loss, thereby causing osteoporosis. However, the role of Nox4 in osteoblasts during early development remains unclear. We used zebrafish to study the effect of Nox4 deletion on bone mineralization in early development. nox4-/- zebrafish showed decreased bone mineralization during early development and significantly reduced numbers of osteoblasts, osteoclasts, and chondrocytes. Transcriptome sequencing showed that the TGF-β signaling pathway was significantly disrupted in nox4-/- zebrafish. Inhibiting TGF-β signaling rescued the abnormal bone development caused by nox4 deletion and increased the number of osteoblasts. We used Saos-2 human osteosarcoma cells to confirm our results, which clarified the role of Nox4 in human osteoblasts. Our results demonstrate the mechanism of reduced bone mineralization in early development and provide a basis for the clinical treatment of osteoporosis.