Mir155 regulates osteogenesis and bone mass phenotype via targeting S1pr1 gene.

MicroRNA-155 (miR155) is overexpressed in various inflammatory diseases and cancer, in which bone resorption and osteolysis are frequently observed. However, the role of miR155 on osteogenesis and bone mass phenotype is still unknown. Here, we report a low bone mass phenotype in the long bone of -Tg mice compared with wild-type mice. In contrast, -KO mice showed a high bone mass phenotype and protective effect against inflammation-induced bone loss. -KO mice showed robust bone regeneration in the ectopic and orthotopic model, but -Tg mice showed compromised bone regeneration compared with the wild-type mice. Similarly, the osteogenic differentiation potential of bone marrow stromal stem cells (BMSCs) from -KO mice was robust and -Tg was compromised compared with that of wild-type mice. Moreover, knockdown in BMSCs from wild-type mice showed higher osteogenic differentiation potential, supporting the results from -KO mice. TargetScan analysis predicted sphingosine 1-phosphate receptor-1 () as a target gene of , which was further confirmed by luciferase assay and knockdown. overexpression in BMSCs robustly promoted osteogenic differentiation without affecting cell viability and proliferation. Furthermore, osteoclastogenic differentiation of -Tg bone marrow-derived macrophages was inhibited compared with that of wild-type mice. Thus, showed a catabolic effect on osteogenesis and bone mass phenotype via interaction with the gene, suggesting inhibition of as a potential strategy for bone regeneration and bone defect healing.