Journal of Bone Research
Open Access
ISSN: 2572-4916
ISSN: 2572-4916
Il-Shin Kim*, Ujjal K Bhawal
Background: Bone Marrow-derived Mesenchymal Stem Cells (BMMSCs) have been extensively studied for their therapeutic role in regenerative medicine. However, their effectiveness in BMMSCs-based therapies is constrained due to the hypoxic microenvironment encountered at injured sites. This study aims to investigate the cellular mechanisms that regulate mitochondrial function through mitophagy in hypoxic BMMSCs to improve their therapeutic potential with minimal adverse effects. Material and Methods: C57BL/6 mouse BMMSCs were subjected to a simulated ischemic environment at hypoxia with 1% O2 for 48 hours. Mitophagy markers, including LC3B and BNIP3, were assessed using quantitative real-time PCR, and Western blotting. The hypoxic response was further characterized by evaluating HIF-1α expression and its role in the transcriptional regulation of mitophagy-related genes. Angiogenic factors, such as VEGF, were also quantified to assess the regenerative potential of hypoxia- preconditioned BMMSCs. Results: Hypoxia significantly increased LC3B and BNIP3 expression, suggesting that hypoxia promotes mitophagy in BMMSCs. HIF-1α level was also elevated in these cells and drove BNIP3 transcription. Furthermore, VEGF expression was upregulated in hypoxic BMMSCs, indicative of enhanced reparative functionality. Conclusion: Hypoxic preconditioning promotes mitophagy and survival and reparative capacity of BMMSCs through the upregulation of BNIP3, among other regulators of key mitophagy
Published Date: 2025-06-30; Received Date: 2025-05-30