SIRT5 promotes the osteo-inductive potential of BMP9 by stabilizing the HIF-1α protein in mouse embryonic fibroblasts

• DOI: 10.1016/j.gendis.2025.101563
• Publication Date: 2025-02-18T08:15:40Z
• Authors: Lu Liu; Fanglin Ye; Yue Jiang; Wenting Liu; Dongmei He; Wenge He; Xiang Gao; Hang Liu; Junyi Liao; Baicheng He; Fang He

Bone morphogenetic protein 9 (BMP9) exhibits remarkable osteogenic potential. However, the intricate mechanisms driving this function of BMP9 remain elusive. This study endeavors to investigate potential role sirtuin 5 (SIRT5) in enhancing BMP9's capacity and decipher underlying molecular pathways. To achieve aim, we employed real-time PCR, western blotting, histochemical staining, a cranial defect repair model assess impact SIRT5 on BMP9-mediated osteogenesis. We utilized immunofluorescent immunoprecipitation assay explore associated mechanisms. Our results revealed that significantly up-regulated BMP9-induced markers, while knockdown reduced their expression. Concurrently, hypoxia-inducible factor 1 subunit alpha (HIF-1α) level was increased by SIRT5, but knockdown. Notably, HIF-1α potentiated SIRT5's ability strengthen potential, whereas silencing effect, which confirmed bone assay. The acetylation malonylation levels were may enhance its stability promote effect. Conversely, reversed these effects promoted degradation HIF-1α. Collectively, our demonstrated could be potentially through stabilizing reducing modification. discovery offer novel strategy accelerate tissue engineering differentiation, it also sheds light possible differentiation.