Work

4632427E13Rik Facilitates Jaw Marrow-Derived Mesenchymal Stem Cells Osteogenesis and Angiogenesis Under Hypoxia Through miR-34a-5p/Aldoa/Hif-1α Pathway

Year: 2026

Type: article

Abstract: INTRODUCTION AND AIMS: The regeneration and repair of maxillofacial bone defects remain a significant clinical challenge. Jaw marrow-derived mesenchymal stem cells (JMMSCs) have attracted considerable attention owing to their favourable biological properties; however, the low survival rate of transplanted MSCs in vivo has substantially limited their therapeutic application. In this study, we demonstrate that hypoxic preconditioning enhances both the osteogenic and angiogenic potential of JMMSCs in vitro and in vivo. METHODS: In vitro, the expression levels of osteogenic and angiogenic-related genes were assessed via qRT-PCR and Western blot following hypoxic preconditioning. In vivo, the impact of hypoxic preconditioning on the bone defect repair capacity of JMMSCs was evaluated. Micro-CT scanning was employed to compare microstructural changes at the defect sites. Microarray analysis identified differentially expressed long noncoding RNAs (lncRNAs) in JMMSCs subjected to hypoxic preconditioning. Subsequent bioinformatics analysis was conducted to explore potential regulatory interactions and key signalling pathways among lncRNAs, miRNAs, and mRNAs, followed by experimental validation. RESULTS: Microarray analysis revealed a significant upregulation of lnc-4632427E13Rik in JMMSCs following hypoxic preconditioning. Mechanistic studies demonstrated that lnc-4632427E13Rik functions as a molecular 'sponge' by sequestering miR-34a-5p, leading to activation of the Aldoa/ERK/Hif-1α signalling axis and subsequent promotion of both angiogenesis and osteogenesis in JMMSCs. CONCLUSION: Our findings reveal hypoxic preconditioning as a highly effective strategy for enhancing the differentiation potential of JMMSCs, and further highlight the therapeutic potential of targeting the lnc-4632427E13Rik/miR-34a-5p/Aldoa axis to improve the bone repair capacity of JMMSCs. CLINICAL RELEVANCE: The lnc-4632427E13Rik/miR-34a-5p/Aldoa axis significantly enhances the efficiency and reliability of bone regeneration, representing a promising therapeutic target for clinical applications in the repair of maxillofacial bone defects.

Source: International Dental Journal

DOI: 10.1016/j.identj.2025.109364