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.

MicroRNA-505 is involved in the regulation of osteogenic differentiation of MC3T3-E1 cells partially by targeting RUNX2

“…Sun et al [24] found that miR-503 promotes bone formation in distraction osteogenesis by suppressing smurf1 expression. Lin et al [25] revealed that miR-130a controls bone marrow mesenchymal stem cell differentiation towards an osteoblastic and adipogenic fate. Until now, there has been no study on the role of miR-505 in the osteogenic differentiation of MC3T3-E1 cells.…”

MiR-130a in the adipogenesis of human SGBS preadipocytes and its susceptibility to androgen regulation

“…Another putative target gene of miR-130a -PPARγexhibited only a trend towards significance in our experiments for a regulation by miR-130a. However, PPARγ regulation by miR-130a has been demonstrated in various organisms including humans [31,32,[40][41][42]. To the best of our knowledge our results are the first detecting AR and ADIPOQ as miR-130a target genes in the context of adipogenesis.…”

“…Vimalraj and Selvamurugan demonstrated that a significant upregulation of miR-130a, among others, was specific for differentiated osteoblast after 14 d in comparison to undifferentiated hMSCs [25]. Recently, Lin and colleagues demonstrated that miR-130a overexpression inhibits the adipogenic differentiation of murine bone marrow derived mesenchymal stem cells, while promoting the osteoblastic differentiation [32]. These results point towards an interference of miR-130a with early phases of adipogenesis.…”

MicroRNA‐130a regulates neurological deficit and angiogenesis in rats with ischaemic stroke by targeting XIAP

“…32 Moreover, miR-130a has also been unravelled to increase osteogenic differentiation and attenuate adipogenic differentiation of bone marrow mesenchymal stem cells. 33 In addition, Li et al have found that miR-130a inhibition protected rat cardiac myocytes from hypoxia-triggered apoptosis, 34 and it has been uncovered that miR-130a alleviated neuronal apoptosis and changes in expression of Bcl-2/Bax and Caspase-3 in cerebral infarction rats. 35 We conducted further experiments to discover that inhibited XIAP reversed the effect of suppressed miR-130a on MCAO rats and OGD-treated neurons.…”