Exosomal miR-100-5p Inhibits Osteogenesis of BMSCs and Angiogenesis of VECs By Suppressing BMPR2/Smad1/5/9 Signaling Pathway

Abstract

Background: Non-traumatic osteonecrosis of the femoral head (NONFH) is a common, progressive, and refractory orthopedic disease. We aimed to figure out whether exosomal miRNA from necrotic bone tissues of the non-traumatic osteonecrosis of the femoral head (NONFH) patients are involved in the pathogenesis of NONFH and reveal the underlying mechanisms.Methods: RT-PCR and western blotting were used to detect the expression of osteogenic, adipogenic and angiogenic markers. ALP staining and Alizarin red s (ARS) staining were used to evaluate osteogenic differentiation of BMSCs. Oil red staining was conducted to test the adipocyte deposition. Tube formation assay was used to study angiogenesis of vascular endothelial cells (VECs). HE staining and IHC staining were used to detect the effect of NONFH-exosomes in vivo. MicroRNA sequencing was conducted to find potential regulators in NONFH-exosomes.Results: The NONFH-exosomes can lead to NONFH-like impairment on BMSCs, HUVECs and rats. MiR-100-5p was upregulated in NONFH-exosomes and could inhibit osteogenesis of BMSCs and angiogenesis of HUVECs by targeting BMPR2.Conclusion: The NONFH-exosomal miR-100-5p can lead to NONFH-like damage by targeting BMPR2 and suppressing BMPR2/SMAD1/5/9 signaling pathway, which may be involved in the pathomechanism of non-traumatic osteonecrosis of the femoral head (NONFH).