Long non-coding RNA H19 mediates mechanical tension-induced osteogenesis of bone marrow mesenchymal stem cells via FAK by sponging miR-138

Bone marrow mesenchymal stem cells (BMMSCs) provide the biological basis for bone reconstruction. Mechanical tension stimulation as a potent modulator is able to promote osteogenic capability of BMMSCs. Long non coding RNAs (LncRNAs) as competing endogenous RNAs (ceRNAs) for microRNAs, are postulated to regulate the osteogenic differentiation of stem cells. However, the mechanism how (whether) IncRNAs mediates tension-induced osteogenesis of BMSCs still remains poor understood. Here, human BMMSCs (hBMMSCs) were subjected to mechanical tension (10%, 0.5 Hz). Results showed that mechanical tension could enhance osteogenic differentiation and increase H19 expression. H19 deficiency suppressed tension-induced osteogenic differentiation, demonstrating that H19 could mediate tension-induced osteogenesis in hBMMSCs. Besides, mechanical tension could suppress miR-138 expression, and down-regulated miR-138 promoted tension induced osteogenesis in hBMMSCs. Luciferase reporter assays illustrated that H19 had binding sites with miR138, and H19 deficiency increased miR-138 level, demonstrating that H19 may act as a ceRNA for miR-138 in hBMMSCs. Luciferase reporter assays also showed that miR-138 could target PTIQ,a gene encoding focal adhesion kinase (FAR). Up-regulated miR-138 impaired increased FAR expression induced by mechaniCal tension. The relationship among H19, miR-138 and FAR under tension condition was further studied. H19 deficiency inhibited FAR expression, which could be partly rescued by knock-downing miR-138. In addition, suppressed tension-induced osteogenic differentiation in H19 defective cells was partly rescued by miR-138 knockdown. Taken together, this study indicated that H19 is a positive regulator in tension-induced osteogenesis of hBMMSCs through acting as a ceRNA for miR-138 and then up-regulating downstream FAR. (C) 2018 Elsevier Inc. All rights reserved.