Curcumin-preconditioned bone marrow mesenchymal stem cell exosomes ameliorate postmenopausal osteoporosis by activating mitophagy in osteoblast-lineage cells.

BACKGROUND

Postmenopausal osteoporosis, driven by oxidative stress and impaired osteoblast function, remains a major health crisis with limited anabolic therapies. Exosomes from curcumin-preconditioned mesenchymal stem cells (MSCs) are promising cell-free therapeutics, yet their cellular targets and molecular mechanisms remain elusive.

METHODS

BMSCs were isolated, pretreated with curcumin, and exosomes were purified by ultracentrifugation. Exploratory scRNA-seq, in vitro H2O2 stress assays, and ovariectomized (OVX) mouse models were employed.

RESULTS

Curcumin pretreatment enhanced exosomal osteogenic potential without altering physicochemical properties. scRNA-seq identified osteoblast-lineage cells as major transcriptional responders. Cur-BMSC-Exo activated PINK1/Parkin-mediated mitophagy, eliminated damaged mitochondria, and restored mitochondrial function. This effect was abrogated by Mdivi1. Systemic Cur-BMSC-Exo administration significantly increased bone volume and trabecular thickness in OVX mice, whereas Mdivi1 abolished these benefits.

CONCLUSION

Cur-BMSC-Exo ameliorates osteoporosis by activating mitophagy in osteoblast-lineage cells, offering a novel cell-free therapeutic strategy.