Exosomes From Hypoxia-Preconditioned Bmscs Improve T2dm Peri-Implant Osteogenesis

Poor peri-implant osseointegration in patients with type 2 diabetes mellitus (T2DM) has become a clinical challenge. Bone marrow mesenchymal stem cells (BMSCs)-derived exosomes play an important role in peri-implant osteogenesis, but the mechanism remains unclear. Improving the therapeutic effect of BMSCs-derived exosomes on peri-implant osteogenesis by means such as hypoxia precondition can help improve the outcomes of implant treatments in T2DM patients. Exosomes derived from hypoxia or normoxia-preconditioned BMSCs were co-cultured with BMSCs and human umbilical vein endothelial cells (HUVECs). The effect of exosomes on BMSCs proliferation was detected by CCK-8 and EdU assay, and the effect on HUVECs angiogenesis was detected by wound healing assay, migration assay, tube formation assay, ELISA, qRT-PCR and Western blot. The effect of exosomes on peri-implant osteogenesis was evaluated in diabetic rats through micro-CT and histological analysis. The differentially expressed miRNAs by hypoxia-preconditioned exosomes were identified by miRNA sequencing. The target genes were predicted by bioinformatics analysis and verified by dual luciferase reporter assay. In vitro experiments indicated that hypoxia preconditioning could elevate exosome production and promote proliferation of BMSCs and angiogenesis of HUVECs. Moreover, Hypo-exos promoted peri-implant osteogenesis in diabetic rats. Further investigation revealed the vital involvement of the miR-106b-5p/HIF-1α axis in promoting peri-implant osteogenesis. Exosomes derived from hypoxia-preconditioned BMSCs could improve the peri-implant osteogenesis in diabetic rats, and the miR-106b-5p/ HIF-1α axis could be the underlying mechanism.