2. Academic Validation
  3. Nox4 promotes osteoblast differentiation through TGF-beta signal pathway

Nox4 promotes osteoblast differentiation through TGF-beta signal pathway

  • Free Radic Biol Med. 2022 Nov 10;193(Pt 2):595-609. doi: 10.1016/j.freeradbiomed.2022.11.016.
Zihou Cao 1,  Gongwen Liu 2,  Hui Zhang 3,  Mingyong Wang 4,  Youjia Xu 5
Affiliations

Affiliations

  • 1 Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.
  • 3 The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
  • 4 Murui Biological Technology Co., Ltd., Suzhou Industrial Park, No.11 Jinpu Road, Suzhou, China. Electronic address: [email protected].
  • 5 Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: [email protected].
PMID: 36372285 DOI: 10.1016/j.freeradbiomed.2022.11.016
Abstract

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.

Keywords

Osteoblasts; Osteoclasts; TGF-β signaling pathway; nox4.

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