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Curcumin-preconditioned bone marrow mesenchymal stem cell exosomes ameliorate postmenopausal osteoporosis by
Chao Li1, Xufeng Jiang1, Kechong Zhou2
1Department of Orthopedics, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, Hubei, China.
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.
