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Transplanted mesenchymal stromal cells are unable to migrate to the bone surface and subsequently improve osteogenesis in glucocorticoid-induced osteoporosis

  • Author Footnotes
    ⁎ These authors contributed equally to this work.
    Xueling Zheng
    ⁎ These authors contributed equally to this work.
    Department of Cell Biology, Zunyi Medical University, Zunyi, Guizhou Province, China
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  • Author Footnotes
    ⁎ These authors contributed equally to this work.
    Wanyuji Wang
    ⁎ These authors contributed equally to this work.
    Department of Cell Biology, Zunyi Medical University, Zunyi, Guizhou Province, China
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  • Sisi Chen
    Department of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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  • Bin Zuo
    Department of Orthopedic Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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  • Jiao Li
    Correspondence: Jiao Li, Zunyi Medical University, West Xuefu road, Zunyi City, Guizhou Province, China.
    Department of Cell Biology, Zunyi Medical University, Zunyi, Guizhou Province, China
    Search for articles by this author
  • Author Footnotes
    ⁎ These authors contributed equally to this work.
Published:February 28, 2023DOI:


      Long-term or high-dose use of glucocorticoids causes bone loss and low bone formation. We previously demonstrated that dexamethasone (Dex) administration caused the shifted differentiation balance of mesenchymal stromal cells (MSCs) to favor adipogenic lineage over osteoblastic lineage, which is one of the key mechanisms for Dex-induced osteoporosis (DIO). These findings indicate that supplementing functional allogeneic MSCs could be a therapeutic strategy for DIO. Here, we found that transplanting MSCs by intramedullary injection had little effect in promoting new bone formation. Fluorescent-labeled lineage tracing revealed that 1 week after transplantation, green fluorescent protein (GFP)-MSCs were found to migrate to the bone surface (BS) in control mice but not in DIO mice. As expected, GFP-MSCs on the BS were mostly Runx2-positive; however, GFP-MSCs located away from the BS failed to differentiate into osteoblasts. We further discovered that the levels of transforming growth factor beta 1 (TGF-β1), one of the main chemokines for MSC migration, is significantly decreased in the bone marrow fluid of DIO mice, which is insufficient to direct MSC migration. Mechanistically, Dex inhibits TGF-β1 expression by down-regulating its promoter activity, which decreases bone matrix–deposited TGF-β1 as well as active TGF-β1 released during osteoclast-mediated bone resorption. This study indicates that blocking MSC migration in osteoporotic BM contributes to bone loss and suggests that MSC mobilization to the BS may be a promising target for treating osteoporosis.

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