Let‐7a promotes periodontal bone regeneration of bone marrow mesenchymal stem cell aggregates via the Fas/FasL‐autophagy pathway

• Published in: Journal of cellular and molecular medicine Vol. 27; no. 24; pp. 4056 - 4068
• Main Authors: Yang, Shiyao, Gao, Jing, Chen, Meng, Sun, Yuting, Qiao, Xin, Mao, Hongchen, Guo, Li, Yu, Yang, Yang, Deqin
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.12.2023; John Wiley and Sons Inc
• Subjects: Antibodies; Apoptosis; Autophagy; Biotechnology; BMMSCs; Bone growth; Bone marrow; Bone Marrow Cells - metabolism; Bone Regeneration - genetics; Cell Differentiation - genetics; Cell growth; Cells, Cultured; cell‐aggregates; Fas/FasL; FasL protein; Laboratory animals; Medical research; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; microRNA; MicroRNAs; Original; Osteogenesis; Osteogenesis - genetics; Penicillin; periodontal regeneration; Polymerase chain reaction; Reagents; Regeneration; Stem cell transplantation; Stem cells; Tissue engineering; Up-Regulation; BMMSCs; Fas/FasL; microRNA; periodontal regeneration; cell-aggregates
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.17988

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.