Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Stomatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China; Department of Stomatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
Biomed Pharmacother. 2020 Nov;131:110672. doi: 10.1016/j.biopha.2020.110672. Epub 2020 Sep 2.
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.
辐射诱导纤维化最近被确定为颌骨放射性骨坏死（ORNJ）的主要原因，抗辐射纤维化药物已取得令人满意的治疗效果。然而，其分子机制仍有待充分阐明。在这项研究中，我们发现辐照激活的牙龈成纤维细胞对人骨髓间充质干细胞（hBMSCs）成骨分化的抑制作用。此外，辐照激活的成纤维细胞在 hBMSCs 中显著增加了 miR-23a 的表达。降低 miR-23a 增强了 BMSCs 的成骨分化，而升高 miR-23a 通过直接靶向 CXCL12 抑制这一过程。最后，辐照激活的成纤维细胞释放的外泌体抑制了 BMSCs 的成骨分化，这些外泌体介导的 miR-23a 的传递进一步调节了 hBMSCs 中的 miR-23a/CXCL12 轴。因此，我们的研究结果表明，在放射治疗中，人牙龈成纤维细胞分泌的外泌体通过转移 miR-23a 在 hBMSCs 的成骨分化中发挥重要作用，这可能为 ORNJ 提供新的临床治疗方法。
