Published online Jul 18, 2025. doi: 10.5312/wjo.v16.i7.107045
Revised: April 14, 2025
Accepted: May 27, 2025
Published online: July 18, 2025
Processing time: 125 Days and 23.4 Hours
Degenerative disc disease (DDD) is characterized by the loss of nucleus pulposus cells (NPCs). Inducing differentiation of bone marrow mesenchymal stem cells (MSCs) into NPCs has emerged as a novel therapeutic strategy for DDD. Ho
To investigate the role and mechanism of miR-365 in promoting the differentiation of MSCs into NPCs for DDD treatment.
In vitro, the effects of miR-365 on MSC proliferation, apoptosis, and differentiation were assessed by cell counting kit-8 assay, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR). In vivo, the expression levels of miR-365, HIF-1α, Sox9, Kdm6a, and HOXA9 in the spinal cord of rats with spinal cord injury were determined by qRT-PCR and Western blot.
In vitro, miR-365 significantly promoted MSC proliferation and inhibited MSC apoptosis. The expression levels of glycosaminoglycans, proteoglycan, and type 2 collagen were significantly increased with miR-365 ectopic expression. In vivo, the expression levels of miR-365, HIF-1α, Sox9, and Kdm6a were significantly increased, whereas HOXA9 was remarkably decreased. Mechanically, miR-365 inhibited HOXA9 expression by directly binding to its 3’ untranslated region. HOXA9 could inhibit HIF-1α expression by binding to the Hif-1α promoter, thereby affecting the expression levels of Sox9 and Kdm6a. Moreover, HOXA9 knockdown significantly reversed the differentiation of MSCs into NPCs induced by miR-365.
miR-365 promotes HOXA9-mediated differentiation of MSCs into NPCs by interacting with HIF-1α and may serve as a potential target for DDD treatment.
Core Tip: This study investigates the role of miR-365 in promoting the differentiation of bone marrow mesenchymal stem cells (MSCs) into nucleus pulposus cells (NPCs) for degenerative disc disease (DDD) treatment. We reveal that miR-365 enhances MSC proliferation and inhibits apoptosis, while promoting NPC-related marker expression. Mechanistically, miR-365 targets HOXA9, which in turn regulates HIF-1α, Sox9, and Kdm6a. This finding highlights miR-365 as a potential therapeutic target for DDD, offering a novel strategy to address the loss of NPCs.