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Extracellular vesicles from GPNMB-modified bone marrow mesenchymal stem cells attenuate bone loss in an
Ba Huang1, Yongwei Su2, Enpu Shen1
1Department of Orthopaedics, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China.
Aims:
The efficacy of anti-osteoporotic treatments is still limited. Our study aimed to investigate the effect of extracellular vesicles (EVs) derived from bone marrow-derived MSCs (BMSCs) overexpressing glycoprotein non-melanoma clone B (GPNMB) on osteoporosis (OP).
Main Methods:
Lentiviral vector for GPNMB overexpression or its negative control was generated and transfected into BMSCs. EVs enriched with GPNMB (GPNMB-EVs) were extracted from GPNMB-modified BMSC-conditioned medium and then identified. Cellular uptake and proliferation were analyzed using the Dil-labeled assay and CCK-8 assay, respectively. Cytochemical staining, western blot, and RT-qPCR analysis were performed to assess the effect of GPNMB-EVs on osteogenic differentiation of BMSCs in vitro. Dickkopf-1 (DKK1) as the inhibitor was applied to explore the Wnt/β-catenin signaling pathway involved in the GPNMB-EV-induced osteogenic differentiation. In vivo experiments were conducted using an ovariectomized (OVX) rat model of postmenopausal osteoporosis, and then assessed the effect of GPNMB-EVs by micro-CT, and histological and immunohistochemical assays.
Key Findings:
GPNMB-EVs were taken up by BMSCs, and they noticeably promoted the proliferation of BMSCs. Additionally, GPNMB-EVs activated the Wnt/β-catenin signaling to stimulate osteogenesis in BMSCs. In vivo examination showed that GPNMB-EVs remarkably improved trabecular bone regeneration and alleviated the osteoporotic phenotype in the OVX-induced rat model of OP.
Significance:
EVs derived from GPNMB-modified BMSCs significantly stimulated the proliferation and osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling and attenuated the bone loss in the OVX-induced rat model of OP. Our findings suggest the promising potential of GPNMB-EVs as cell-free therapy for the treatment of OP.
Insights
Extracellular vesicles (EVs) engineered to overexpress GPNMB promote bone regeneration. These GPNMB-EVs stimulate bone marrow-derived stem cell proliferation and osteogenic differentiation, offering a potential cell-free therapy for osteoporosis.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Cell Biology
Background:
- Current osteoporosis treatments have limited efficacy.
- Extracellular vesicles (EVs) show therapeutic potential.
- Bone marrow-derived mesenchymal stem cells (BMSCs) are key in bone regeneration.
Purpose of the Study:
- To investigate the therapeutic effect of GPNMB-overexpressing EVs derived from BMSCs on osteoporosis.
- To explore the underlying mechanisms of GPNMB-EVs in promoting osteogenesis.
Main Methods:
- Generated lentiviral vectors for GPNMB overexpression in BMSCs.
- Isolated and characterized GPNMB-enriched EVs (GPNMB-EVs).
- Assessed BMSC proliferation and osteogenic differentiation in vitro.
- Utilized an ovariectomized (OVX) rat model for in vivo osteoporosis assessment.
Main Results:
- GPNMB-EVs were effectively internalized by BMSCs and promoted their proliferation.
- GPNMB-EVs significantly enhanced osteogenic differentiation by activating the Wnt/β-catenin signaling pathway.
- In vivo studies demonstrated that GPNMB-EVs improved trabecular bone regeneration and alleviated osteoporosis in OVX rats.
Conclusions:
- GPNMB-modified BMSCs-derived EVs stimulate BMSC proliferation and osteogenic differentiation via Wnt/β-catenin signaling.
- GPNMB-EVs effectively attenuate bone loss in an OVX-induced osteoporosis rat model.
- GPNMB-EVs represent a promising cell-free therapeutic strategy for treating osteoporosis.
