期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 193, 期 -, 页码 595-609出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2022.11.016
关键词
nox4; TGF-? signaling pathway; Osteoclasts; Osteoblasts
资金
- National Key R&D Program of China [2021YFC2501702]
- Natural Science Foundation of China [82072474]
- Gusu Health Talent Program [GSWS2020024]
- Geriatrics Clinical Technology Application Research Project [LR2021022]
- Jiangsu Province Applied Engineering Research Center of Physical And Medical Fusion Promoting Bone Health In The Elderly Natural Science Foundation of China [SYS2018050]
This study investigates the role of Nox4 in early bone development and finds that Nox4 deletion leads to reduced bone mineralization and significantly decreased numbers of osteoblasts, osteoclasts, and chondrocytes. The study also reveals disruption of the TGF-beta signaling pathway in the absence of Nox4, and demonstrates that inhibiting this signaling pathway rescues the abnormal bone development and increases the number of osteoblasts.
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 devel-opment 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 signifi-cantly reduced numbers of osteoblasts, osteoclasts, and chondrocytes. Transcriptome sequencing showed that the TGF-beta signaling pathway was significantly disrupted in nox4-/-zebrafish. Inhibiting TGF-beta 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.
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