Mechanical unloading leads to @entity604 and @entity2537 partly due to impaired osteoblastogenesis of bone marrow stromal cells (BMSCs). However, the underlying molecular mechanisms of this phenomenon are not fully understood. In this study, we demonstrated that cyclic mechanical stretch (CMS) promotes osteoblastogenesis of BMSCs both in vivo and in vitro. Besides, we found that Hedgehog (Hh) signaling pathway was activated in this process. Inhibition of which by either knockdown of @entity6832 ( @entity6832 ) or treating BMSCs with Hh inhibitors attenuated the osteogenic effect of CMS on BMSCs, suggesting that Hh signaling pathway acts as an endogenous mediator of mechanical stimuli on BMSCs. Furthermore, we demonstrated that @entity6832 expression level was regulated by DNA methylation mechanism. Chromatin Immunoprecipitation (ChIP) assay showed that @entity15701 ( @entity15701 ) binds to @entity6832 gene promoter, leading to DNA hypermethylation in mechanical unloading BMSCs. However, mechanical stimulation down-regulates the protein level of @entity15701 , results in DNA demethylation and @entity6832 expression. More importantly, we found that inhibition of @entity15701 partly rescued @entity604 in HU @entity19 by mechanical unloading. Our results demonstrate, for the first time, that mechanical stimulation regulates osteoblastic genes expression via direct regulation of @entity15701 , and the therapeutic inhibition of @entity15701 may be an efficient strategy for enhancing bone formation under mechanical unloading.

Mechanical stimulation promote the osteogenic differentiation of bone marrow stromal cells through epigenetic regulation of XXXX .

@entity19 :: ('10090', 'Species') :: ['mice'] @entity604 :: ('MESH:D016301', 'Disease') :: ['bone loss'] @entity2537 :: ('MESH:D020966', 'Disease') :: ['disuse osteoporosis'] @entity6832 :: ('20423(Tax:10090)', 'Gene') :: ['Sonic hedgehog', 'Shh'] @entity15701 :: ('13436(Tax:10090)', 'Gene') :: ['DNA methyltransferase 3b', 'Dnmt3b']
@entity6832 :: (20423(Tax:10090),Gene) :: ['Sonic Hedgehog']
