MiR-764-5p Promotes Osteoblast Differentiation Through Inhibition Of CHIP Expression

MicroRNAs(miRNAs) are a recently characterized class of small (~22nucleotides) endogenous non-coding RNAs that band to the3’-UTR of targetedgenes to mediate inhibition of translation of proteins.In this study, we found thatCHIP(C terminus of Hsc70-interacting protein)/STUB1enhances thetranscription of Runx2by inhibiting the expression of CHIP and also promotesthe differentiation of osteoblast.CHIP is a member of U-box protein of E3ligase family and plays importantrole in bone, skeletal muscle, heart, nervous system and other tissuedevelopment.Differentiation of committed precursor cells into the osteoblast lineage istightly regulated by several factors including Runx2and BMP2. We previouslyreported that CHIP negatively regulated osteoblast differentiation throughpromoting Runx2protein degradation. However, how CHIP is regulated duringosteoblast differentiation remains unknown. In this study, we found thatmiR-764-5p is up expressed during the osteoblast differentiation in calvarial andosteoblast progenitor cells, coupled with down expression of CHIP protein. Weobserved that forced expression or inhibition of miR-764-5p decreased orincreased the CHIP protein level through affecting its translation by targetingthe3’-UTR region. Perturbation of miR-764-5p resulted in altereddifferentiation fate of osteoblast progenitor cells and the role of miR-764-5pwas reversed by over-expression of CHIP while depletion of CHIP impaired theeffect of miR-764-5p. Our data demonstrated that miR-764-5p positivelyregulates osteoblast differentiation from osteoblast progenitor cells byrepressing the translation of CHIP protein.