miR-764-5p promotes osteoblast differentiation through inhibition of CHIP/STUB1 expression

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. © 2012 American Society for Bone and Mineral Research.