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Let-7a promotes periodontal bone regeneration of bone marrow mesenchymal stem cell aggregates via the Fas/FasL-autophagy pathway
Authors:Shiyao Yang  Jing Gao  Meng Chen  Yuting Sun  Xin Qiao  Hongchen Mao  Li Guo  Yang Yu  Deqin Yang
Institution:1. 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

Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China

Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), ​Investigation (equal), Methodology (equal), Resources (lead), Software (equal), Writing - original draft (equal), Writing - review & editing (equal);2. 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

Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China

Contribution: Conceptualization (equal), Data curation (equal), Formal analysis (equal), ​Investigation (equal), Project administration (equal), Writing - original draft (equal);3. Department of Oral and Maxillofacial Surgery, Daping Hospital, Army Medical University, Chongqing, China

Contribution: Conceptualization (supporting), Data curation (supporting), ​Investigation (supporting), Methodology (supporting), Software (supporting);4. 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

Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China

Contribution: Methodology (supporting), Software (supporting);5. Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, China

Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, China

Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing, China

Contribution: Methodology (supporting), Software (supporting);6. Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, China

Abstract: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.
Keywords:BMMSCs  cell-aggregates  Fas/FasL  microRNA  periodontal regeneration
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