Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, China.
Free Radic Biol Med. 2022 Nov 20;193(Pt 2):595-609. doi: 10.1016/j.freeradbiomed.2022.11.016. Epub 2022 Nov 10.
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.
烟酰胺腺嘌呤二核苷酸磷酸氧化酶 4（Nox4）是活性氧的主要来源，它促进破骨细胞的形成，导致骨丢失，从而引起骨质疏松症。然而，Nox4 在早期发育过程中对成骨细胞的作用尚不清楚。我们使用斑马鱼来研究 Nox4 缺失对早期发育过程中骨矿化的影响。nox4 斑马鱼在早期发育过程中表现出骨矿化减少，成骨细胞、破骨细胞和软骨细胞数量明显减少。转录组测序显示，nox4 斑马鱼中的 TGF-β 信号通路显著受到破坏。抑制 TGF-β 信号通路可挽救 nox4 缺失引起的异常骨发育，并增加成骨细胞数量。我们使用人骨肉瘤 Saos-2 细胞来证实我们的结果，这阐明了 Nox4 在人成骨细胞中的作用。我们的研究结果揭示了早期发育过程中骨矿化减少的机制，为骨质疏松症的临床治疗提供了依据。
