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LncRNA/mRNA expression profile of rat bone marrow mesenchymal stem cells (BMSCs) under hypoxia condition

ABSTRACT: The osteonecrotic area of steroid-induced avascular necrosis of the femoral head (SANFH) is a hypoxic microenvironment that leads to apoptosis of transplanted bone marrow mesenchymal stem cells (BMSCs). However, the underlying mechanism remains unclear. Here, we explore the mechanism of hypoxic-induced apoptosis of BMSCs, and use the mechanism to improve the transplantation efficacy of BMSCs. We analyzed LncRNA/mRNA expression profile of BMSCs under hypoxia conditions, and successfully screened the key long non-coding RNA AABR07053481 (LncAABR07053481) which mediated hypoxic apoptosis of BMSCs, we further determined its regulatory mechanism. Importantly, overexpression of LncAABR07053481 can improve the survival rate and repair efficacy of BMSCs under hypoxia conditions.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE225572 | GEO | 2023/02/18

REPOSITORIES: GEO

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Project description:Rationale：Poor peri-implant osseointegration of dental implants in patients with type II diabetes has become a major clinical challenge in recent years. MSC (Mesenchymal stem cell)-derived exosomes may play an important role in peri-implant osseointegration, but the mechanism remains unclear. Enhancing the therapeutic effect of MSC-derived exosomes and exploring the potential mechanism can help provide a new therapeutic strategy to improve the clinical outcome of dental implant restorations in patients with type II diabetes. Methods：The exosomes derived from hypoxia (Hypo-exos) or normoxia (Nor-exos) preconditioned bone marrow mesenchymal stem cells (BMSCs) were co-cultured with BMSCs and human umbilical vein endothelial cells (HUVECs). The effect of exosomes on BMSCs cell proliferation was detected by CCK-8 assay and EdU assay, and the effect on angiogenesis ability of HUVECs was detected by wound healing assay, transwell migration assay, tube formation assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. A diabetic rat dental implant model was also established and the effect of exosomes on implant osseointegration was evaluated through micro-CT scanning and histological analysis. The differentially expressed miRNAs between Hypo-exos and Nor-exos were identified by high-throughput miRNA sequencing. Subsequently, the target genes and their roles in regulating angiogenesis were predicted and analyzed by bioinformatics analysis and dual luciferase reporter assay. Results：In vitro experiments indicated that hypoxia preconditioning could elevate exosome production and promote cell proliferation of BMSCs and angiogenesis of HUVECs. Moreover, Hypo-exos promoted peri-implant osteogenesis in rats with diabetes. Further investigation revealed the vital involvement of the miR-106b-5p/HIF-1α axis in promoting peri-implant osseointegration. Conclusion: Exosomes derived from hypoxia-preconditioned BMSCs could improve the peri-implant osseointegration in rats with diabetes by promoting cell proliferation and angiogenesis, and the miR-106b-5p/ HIF-1α axis could be the underlying mechanism.

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LncRNA/mRNA expression profile of rat bone marrow mesenchymal stem cells (BMSCs) under hypoxia condition

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