Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, China.
Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China.
J Cell Mol Med. 2023 Dec;27(24):4056-4068. doi: 10.1111/jcmm.17988. Epub 2023 Oct 19.
Periodontal bone regeneration using bone marrow mesenchymal stem cell (BMMSC) transplantation is a promising method; however, the method for osteogenic differentiation of BMMSCs needs to be improved. In this research, we sought to identify the roles of let-7a in the osteogenesis of BMMSCs and to provide a potential method for periodontal bone regeneration. Our previous study revealed that Fas/FasL is a target of let-7a. In this study, we demonstrated that let-7a overexpression significantly enhanced BMMSC-CAs osteogenesis both in vitro and in vivo. Mechanistically, upregulation of Fas/FasL using the rfas/rfaslg plasmid obstructed the osteogenesis of BMMSCs by inhibiting autophagy. Furthermore, we confirmed that overexpression of let-7a activated autophagy and alleviated the inhibited osteogenesis by the autophagy inhibitor 3-MA and the rfas/rfaslg plasmid of BMMSCs. In general, our findings showed that let-7a promoted the osteogenesis of BMMSCs through the Fas/FasL-autophagy pathway, suggesting that the application of let-7a in BMMSC-CAs based periodontal bone regeneration could be a promising strategy.
利用骨髓间充质干细胞（BMMSC）移植进行牙周骨再生是一种很有前途的方法；然而，BMMSCs 的成骨分化方法仍需要改进。在这项研究中，我们试图确定 let-7a 在 BMMSCs 成骨中的作用，并为牙周骨再生提供一种潜在的方法。我们之前的研究表明 Fas/FasL 是 let-7a 的一个靶标。在这项研究中，我们证明 let-7a 的过表达显著增强了 BMMSC-CAs 的体外和体内成骨作用。机制上，使用 rfas/rfaslg 质粒上调 Fas/FasL 通过抑制自噬来阻碍 BMMSCs 的成骨作用。此外，我们证实 let-7a 的过表达激活了自噬，并缓解了自噬抑制剂 3-MA 和 rfas/rfaslg 质粒对 BMMSCs 成骨的抑制作用。总的来说，我们的研究结果表明 let-7a 通过 Fas/FasL-自噬途径促进 BMMSCs 的成骨作用，这表明 let-7a 在基于 BMMSC-CAs 的牙周骨再生中的应用可能是一种很有前途的策略。
