@article{Liu2025, 
author = {Lu Liu and Fanglin Ye and Yue Jiang and Wenting Liu and Dongmei He and Wenge He and Xiang Gao and Hang Liu and Junyi Liao and Baicheng He and Fang He},
title = {SIRT5 promotes the osteo-inductive potential of BMP9 by stabilizing the HIF-1α protein in mouse embryonic fibroblasts},
year = {2025},
journal = {Genes & Diseases},
volume = {12},
number = {4},
pages = {101563},
keywords = {BMP9, HIF-1α, Osteogenic differentiation, Post-translation modification, SIRT5},
url = {https://www.sciopen.com/article/10.1016/j.gendis.2025.101563},
doi = {10.1016/j.gendis.2025.101563},
abstract = {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 the potential role of sirtuin 5 (SIRT5) in enhancing BMP9’s osteogenic capacity and decipher the underlying molecular pathways. To achieve this aim, we employed real-time PCR, western blotting, histochemical staining, and a cranial defect repair model to assess the impact of SIRT5 on BMP9-mediated osteogenesis. We utilized real-time PCR, western blotting, immunofluorescent staining, and immunoprecipitation assay to explore the associated mechanisms. Our results revealed that SIRT5 significantly up-regulated BMP9-induced osteogenic markers, while SIRT5 knockdown reduced their expression. Concurrently, hypoxia-inducible factor 1 subunit alpha (HIF-1α) level was increased by SIRT5, but reduced by SIRT5 knockdown. Notably, HIF-1α potentiated the SIRT5’s ability to strengthen BMP9’s osteogenic potential, whereas HIF-1α silencing reduced this effect, which was confirmed by bone defect repair assay. The acetylation and malonylation levels of HIF-1α were reduced by SIRT5, which may enhance its stability to promote BMP9’s osteogenic effect. Conversely, SIRT5 knockdown reversed these effects and promoted the degradation of HIF-1α. Collectively, our results demonstrated that the BMP9’s osteogenic potential could be promoted by SIRT5, potentially through stabilizing HIF-1α by reducing its acetylation and malonylation modification. This discovery may offer a novel strategy to accelerate bone tissue engineering by enhancing osteogenic differentiation, and it also sheds light on the possible mechanisms underlying BMP9-mediated osteogenic differentiation.}
}