Exosome secreted by human gingival fibroblasts in radiation therapy inhibits osteogenic differentiation of bone mesenchymal stem cells by transferring miR-23a.
Exosome secreted by human gingival fibroblasts in radiation therapy inhibits osteogenic differentiation of bone mesenchymal stem cells by transferring miR-23a.
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DOI：
10.1016/j.biopha.2020.110672
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发表时间：
2020-09
期刊：
影响因子：
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通讯作者：
Xiu-mei Zhuang;Bin Zhou
中科院分区：
文献类型：
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作者：
Xiu-mei Zhuang;Bin Zhou
放射性纤维化是近年来确立的颌骨放射性骨坏死(ORNJ)的主要原因，抗放射性纤维化药物取得了满意的治疗效果。然而，其分子机制仍未完全阐明。在本研究中，我们发现辐射激活的牙龈成纤维细胞对人骨髓间充质干细胞(HBMSCs)的成骨分化有抑制作用。此外，辐射激活的成纤维细胞显著增加了人骨髓间充质干细胞miR-23a的表达。MiR-23a的降低促进了BMSCs的成骨分化，而miR-23a的升高通过直接靶向CXCL12抑制了这一过程。最后，辐射激活的成纤维细胞释放的外切体抑制骨髓间充质干细胞的成骨分化，这些外切体介导miR-23a的转运，进而调节hBMSCs的miR-23a/CXCL12轴。因此，我们的研究结果表明，放射治疗中人牙龈成纤维细胞分泌的外切体通过转移miR-23a在hBMSCs的成骨分化中起重要作用，这可能为临床治疗ORNJ提供新的途径。
Radiation-induced fibrosis is recently established as a main reason for osteoradionecrosis of the jaw (ORNJ), anti-eradiation fibrosis drugs achieve satisfactory therapeutic effects. However, the molecular mechanism remain to be fully elucidated. In this study, we found the inhibitory effect of irradiation activated gingival fibroblasts on osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). Moreover, irradiation-activated-fibroblasts significantly increased miR‑23a expression in hBMSCs. Decreased miR‑23a enhanced osteogenic differentiation of BMSCs, and elevated miR‑23a inhibited this process via directly targeting CXCL12. Finally, exosome released from irradiation-activated-fibroblasts inhibited osteogenic differentiation of BMSCs, and these exosome mediated delivery of miR-23a and further regulated miR-23a/CXCL12 axis in hBMSCs. Therefore, our findings suggest that by transferring miR-23a, exosome secreted by human gingival fibroblasts in radiation therapy serves a vital role in osteogenic differentiation of hBMSCs, which may provide novel clinical treatments for ORNJ.