title: miR-764-5p promotes osteoblast differentiation through inhibition of CHIP/STUB1 expression.
abstract: Differentiation of committed precursor cells into the osteoblast lineage is tightly regulated by several factors, including Runx2 and BMP2. We previously reported that C terminus of Hsc70-interacting protein/STIP1 homology and U-Box containing protein 1 (CHIP/STUB1) negatively regulated osteoblast differentiation through promoting Runx2 protein degradation. However, how CHIP is regulated during osteoblast differentiation remains unknown. In this study, we found that miR-764-5p is up-expressed during the osteoblast differentiation in calvarial and osteoblast progenitor cells, coupled with down-expression of CHIP protein. We observed that forced expression or inhibition of miR-764-5p decreased or increased the CHIP protein level through affecting its translation by targeting the 3'-UTR region. Perturbation of miR-764-5p resulted in altered differentiation fate of osteoblast progenitor cells and the role of miR-764-5p was reversed by overexpression of CHIP, whereas depletion of CHIP impaired the effect of miR-764-5p. Our data showed that miR-764-5p positively regulates osteoblast differentiation from osteoblast progenitor cells by repressing the translation of CHIP protein.
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Medicine, Tsinghua University, Beijing, China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Guo
authors.forename: Fangli
authors.initials: F
authors.lastname: Ren
authors.forename: Yinyin
authors.initials: Y
authors.lastname: Wang
authors.forename: Shan
authors.initials: S
authors.lastname: Li
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Gao
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Ning
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wu
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.forename: Shek Man
authors.initials: SM
authors.lastname: Chim
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Chang
mesh_terms: D020413:3' Untranslated Regions; D016475:3T3 Cells; D000818:Animals; D002454:Cell Differentiation; D005786:Gene Expression Regulation; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism* / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology*; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; D050883:HSC70 Heat-Shock Proteins; D007074:Immunoglobulin G; C576122:MIRN764 microRNA, mouse; D035683:MicroRNAs; C467728:STUB1 protein, human; C492951:Stub1 protein, mouse; D044767:Ubiquitin-Protein Ligases