LOC103691336/miR-138-5p/BMPR2 axis modulates Mg-mediated osteogenic differentiation in rat femoral fracture model and rat primary bone marrow stromal cells.

Abstract

Intramedullary stabilization is frequently used to treat long bone fractures. Since implant removal can become technically very challenging with the potential to cause further tissue damage, biodegradable materials are emerging as alternative options. Magnesium (Mg)-based biodegradable implants have a controllable degradation rate and good tissue compatibility, which makes them attractive for musculoskeletal research. Herein, the degradation of Mg and steel implants, the pathological characteristics and osteoblast differentiation in mice femora were examined. To investigate the molecular mechanism, we analyzed the differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in Mg-implanted or stain-steel-implanted callus tissues. lncRNA LOC103691336 was upregulated in Mg-implanted tissues and most relevant to BMPR2, a kinase receptor of BMPs with an established role in osteogenesis. The knockdown of LOC103691336 attenuated Mg-mediated osteogenic differentiation. Furthermore, miR-138-5p, previously reported to inhibit osteogenic differentiation, could bind to LOC103691336 and BMPR2 in bone marrow stromal cells (BMSCs). LOC103691336 competed with BMPR2 for miR-138-5p binding in BMSCs to attenuate the inhibitory effect of miR-138-5p on BMPR2 expression. Finally, the effect of LOC103691336 knockdown on Mg-mediated osteogenic differentiation could be attenuated by miR-138-5p inhibition. In conclusion, we provided a novel mechanism of Mg implants mediating the osteogenesis differentiation and demonstrated that Mg implants may be promising for improving fracture healing.