Curcumin (CUR) was reported to stimulate the expression of methyltransferase‐like 3 (METTL3), a potential new target for the replacement therapy of osteoporosis. Besides, marrow stem cells (MSC)-derived exosomes (EXO) were proven to improve osteoporosis by promoting the proliferation of osteoblasts. In this study, we aimed to study the effect of CUR and BMSC-derived exosomes in the treatment of osteoporosis.

Material and methods:
Microscopy was used to characterize exosomes derived from bone marrow stem cells (BMSCs). MicroCT was carried out to analyze the parameters of bone formation. Western blot was carried out to analyze the expression of surface markers on BMSC-derived exosomes and METTL3/Runt-related transcription factor 2 (RUNX2) proteins under different conditions. Real-time PCR was used to assess the gene expression under different circumstances.

The exosomes derived from CUR-treated BMSCs showed an enhanced therapeutic effect on osteoporosis mice compared with exosomes derived from untreated BMSCs. Mechanistically, the effect of BMSC-derived exosomes on restoring the de-regulated expression of METTL3, miR-320 and RUNX2 was significantly enhanced by CUR treatment upon BMSCs. Besides, CUR treatment upon BMSCs showed an obvious effect on enhancing the stimulatory role of BMSC-derived exosomes in the expression of METTL3, miR-320, RUNX2, BGLAP and LAP in BMSCs. Furthermore, luciferase assay demonstrated that miR-320 was capable of suppressing the expression of RUNX2 through binding to the 3’ UTR of RUNX2.

Our study demonstrated that BMSC-derived exosomes could modulate the METTL3/miRNA-320/RUNX2 axis to attenuate osteoporosis by promoting osteogenic differentiation of BMSCs. Moreover, the CUR treatment upon BMSCs promoted the therapeutic effect of BMSC-derived exosomes.