PT - JOURNAL ARTICLE AU - Zhichao Zheng AU - Lihong Wu AU - Zhicong Li AU - Ruoshu Tang AU - Hongtao Li AU - Yinyin Huang AU - Zhitong Ye AU - Dong Xiao AU - Xiaolin Lin AU - Gang Wu AU - Richard T Jaspers AU - Janak L. Pathak TI - MicroRNA-155 regulates osteogenesis and bone mass phenotype via targeting S1PR1 gene AID - 10.1101/2022.02.18.480982 DP - 2022 Jan 01 TA - bioRxiv PG - 2022.02.18.480982 4099 - http://biorxiv.org/content/early/2022/02/19/2022.02.18.480982.short 4100 - http://biorxiv.org/content/early/2022/02/19/2022.02.18.480982.full AB - 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 miR155-Tg mice compared with control mice. In contrast, miR155-KO mice showed a high bone mass phenotype. miR155-KO mice showed robust bone regeneration in the ectopic and orthotopic model, but miR155-Tg mice showed compromised bone regeneration compared with the control mice. Similarly, the osteogenic differentiation potential of bone marrow stromal stem cells (BMSCs) from miR155-KO mice was robust and miR155-Tg was compromised compared with that of control mice. Moreover, miR155 knockdown in BMSCs from control mice showed higher osteogenic differentiation potential, supporting the results from miR155-KO mice. TargetScan analysis predicted S1PR1 as a target gene of miR155, which was further confirmed by luciferase assay and miR155 knockdown. S1PR1 overexpression in BMSCs robustly promoted osteogenic differentiation without affecting cell viability and proliferation. Thus, miR155 showed a catabolic effect on osteogenesis and bone mass phenotype via interaction with the S1PR1 gene, suggesting inhibition of miR155 as a potential strategy for bone regeneration and bone defect healing.Competing Interest StatementThe authors have declared no competing interest.