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...

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Bibliographic Details
Published in:	eLife Vol. 12
Main Authors:	Zheng, Zhichao, Wu, Lihong, Li, Zhicong, Tang, Ruoshu, Li, Hongtao, Huang, Yinyin, Wang, Tianqi, Xu, Shaofen, Cheng, Haoyu, Ye, Zhitong, Xiao, Dong, Lin, Xiaolin, Wu, Gang, Jaspers, Richard T, Pathak, Janak L
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 04-01-2023 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Subjects:	Analysis Animals Bone and Bones - metabolism Bone cancer Bone Density Bone growth Bone healing Bone loss Bone marrow Bone Marrow Cells - metabolism Bone mass Bone resorption Bones Cancer Cell Biology Cell Differentiation Cell viability Cells, Cultured Density Gene expression Genes Genetic aspects Genetic research Genotype & phenotype Homeostasis Inflammatory diseases Long bone Macrophages Mice MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miR155 miRNA Osteoclastogenesis Osteogenesis Osteolysis Pathophysiology Phenotypes Regeneration S1PR1 Sphingosine 1-phosphate Stem cell transplantation Stem cells Stem Cells and Regenerative Medicine Tissue engineering China bone mass mouse stem cells cell biology cell viability miR155 regenerative medicine S1PR1 osteogenesis
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.77742