Cellular Signalling · Oct 27, 2026

Mechanistic study on the promotion of osteogenic differentiation in osteoporotic rats by moxibustion via regulation of BMSCs-derived exosomal miR-27a-3p-mediated mitophagy

By Li X, Li X, Tjahjono AW et al.

AIMS: To investigate the effects of moxibustion (MOX) on bone loss and osteogenic differentiation in ovariectomized (OVX) rats and determine whether these effects are mediated by mitophagy through bone marrow mesenchymal stem cells (BMSCs)-derived exosomal miR-27a-3p. METHODS: The study was conducted in three stages. In stage 1, sham-operated (SO), OVX, and OVX + MOX rats were evaluated by micro-computed tomography (micro-CT) to assess bone mass and by Alizarin Red S (ARS) staining to evaluate osteogenic differentiation. Autophagy-related markers were also examined, and mitochondrial-lysosomal colocalization was assessed by immunofluorescence. In stage 2, the mitophagy inhibitor Mdivi-1 was administered to OVX + MOX rats to determine the contribution of mitophagy to the effects of MOX. Sequencing analysis and TargetScan prediction identified a potential regulatory relationship between miR-27a-3p and the mitophagy-related gene PINK1, which was subsequently validated using a dual-luciferase reporter assay. In stage 3, miR-27a-3p agomir and antagomir were used to investigate the involvement of the miR-27a-3p-mitophagy axis. RESULTS: MOX increased bone mineral density, improved bone microarchitecture, and enhanced osteogenic differentiation in OVX rats, accompanied by increased mitophagy. Mdivi-1 attenuated these beneficial effects, exacerbating bone loss and reducing osteogenic gene expression, mineralized nodule formation, mitochondrial membrane potential, and mitophagy. The dual-luciferase reporter assay confirmed that PINK1 is a direct target of miR-27a-3p. Inhibition of miR-27a-3p with an antagomir impaired bone microarchitecture, mitophagy, and osteogenesis. Conversely, MOX produced effects comparable to those of the miR-27a-3p agomir, with both interventions promoting osteogenic differentiation through the miR-27a-3p-mitophagy axis. CONCLUSIONS: MOX attenuates bone loss in OVX-induced osteoporosis (OP) by promoting osteogenic differentiation. These effects may be mediated, at least in part, by activation of mitophagy through the BMSCs-associated miR-27a-3p/PINK1 axis, providing a potential mechanistic basis for the therapeutic effects of MOX in OP.

doi.org/10.1016/j.cellsig.2026.112962PubMed 42946315Interventions