MicroRNA‐130a controls bone marrow mesenchymal stem cell differentiation towards the osteoblastic and adipogenic fate

Abstract Objectives With age, bone marrow mesenchymal stem cells (BMSC) have reduced ability of differentiating into osteoblasts but have increased ability of differentiating into adipocytes which leads to age‐related bone loss. MicroRNAs (miRNAs) play major roles in regulating BMSC differentiation. This paper explored the role of miRNAs in regulating BMSC differentiation swift fate in age‐related osteoporosis. Material and methods Mice and human BMSC were isolated from bone marrow, whose miR‐130a level was measured. The abilities of BMSC differentiate into osteoblast or fat cell under the transfected with agomiR‐130a or antagomiR‐130a were analysed by the level of ALP, osteocalcin, Runx2, osterix or peroxisome proliferator‐activated receptorγ (PPARγ), Fabp4. Related mechanism was verified via qT‐PCR, Western blotting (WB) and siRNA transfection. Animal phenotype intravenous injection with agomiR‐130a or agomiR‐NC was explored by Micro‐CT, immunochemistry and calcein double‐labelling. Results MiR‐130a was dramatically decreased in BMSC of advanced subjects. Overexpression of miR‐130a increased osteogenic differentiation of BMSC and attenuated adipogenic differentiation in BMSC, conversely, Inhibition of miR‐130a reduced osteogenic differentiation and facilitated lipid droplet formation. Consistently, overexpression of miR‐130a in elderly mice dropped off the bone loss. Furthermore, the protein levels of Smad regulatory factors 2 (Smurf2) and PPARγ were regulated by miR‐130a with an negative effect through directly combining the 3'UTR of Smurf2 and PPARγ. Conclusions The results indicated that miR‐130a promotes osteoblastic differentiation of BMSC by negatively regulating Smurf2 expression and suppresses adipogenic differentiation of BMSC by targeting the PPARγ, and supply a new target for clinical therapy of age‐related bone loss.