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.
Keywords: adipogenesis; age; cell differentiation; osteogenesis; osteoporosis.
© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.