Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

摘要: Mechanical stimulation and histone deacetylases (HDACs) have essential roles in regulating the osteogenic differentiation of bone marrow stromal cells (BMSCs) formation. However, little is known regarding what regulates HDAC expression therefore BMSCs during osteogenesis. In this study, we investigated whether mechanical loading directly examined role HDACs loading-triggered We first studied microarrays samples from patients with osteoporosis found that NOTCH pathway skeletal development gene sets were downregulated osteoporosis. Then demonstrated stimuli can regulate osteogenesis formation both vivo vitro. signaling was upregulated cyclic stretch (CMS)-induced differentiation, whereas HDAC1 protein downregulated. The perturbation also had a significant effect on matrix mineralization JAG1-mediated Notch signaling, suggesting acts as an endogenous attenuator mechanotransduction BMSCs. Chromatin immunoprecipitation (ChIP) assay results suggest modulates CMS-induced H3 acetylation level at JAG1 promoter. More importantly, inhibitory Hdac1 response to hindlimb unloading mice, pretreatment inhibitor partly rescued caused by unloading. Our demonstrate, for time, orchestrates genes involved via direct regulation HDAC1, therapeutic inhibition may be efficient strategy enhancing under stimulation.