Microbiota and their metabolites short-chain fatty acids (SCFAs) have important roles in regulating tissue regeneration and mesenchymal stem cell (MSC) differentiation. In this study, we explored the potential effects of SCFAs on murine incisor regeneration and dental MSCs. We observed that SCFA deficiency induced by depletion of microbiota through antibiotic treatment led to lower renewal rate and delayed dentinogenesis in mice incisors. Supplementation with SCFAs in drinking water during antibiotic treatment can rescue the renewal rate and dentinogenesis effectively. In vitro, stimulation with SCFAs could promote differentiation of dental MSCs to odontoblasts. We further found that SCFAs could contribute to dentinogenic differentiation of dental MSCs by increasing bone morphogenetic protein (BMP) signal activation. SCFAs could inhibit deacetylation and increase BMP7 transcription of dental MSCs, which promoted BMP signaling. Our results suggested that SCFAs were required for incisor regeneration as well as differentiation of dental MSCs. Microbiota and their metabolites should be concerned as important factors in the tissue renewal and regeneration.

中文翻译：

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微生物群衍生的短链脂肪酸通过抑制组蛋白脱乙酰化促进 BMP 信号传导，并有助于鼠门牙再生中的牙本质分化。

微生物群及其代谢产物短链脂肪酸 (SCFA) 在调节组织再生和间充质干细胞 (MSC) 分化方面具有重要作用。在这项研究中，我们探讨了 SCFAs 对鼠门牙再生和牙齿 MSCs 的潜在影响。我们观察到，通过抗生素治疗导致微生物群耗竭导致 SCFA 缺乏导致小鼠门牙更新率降低和牙本质生成延迟。在抗生素治疗期间在饮用水中补充SCFAs可以有效地挽救更新率和牙本质生成。在体外，SCFAs 的刺激可以促进牙齿间充质干细胞向成牙本质细胞的分化。我们进一步发现 SCFAs 可以通过增加骨形态发生蛋白 (BMP) 信号激活促进牙齿 MSCs 的牙本质分化。SCFAs 可以抑制脱乙酰作用并增加牙齿间充质干细胞的 BMP7 转录，从而促进 BMP 信号传导。我们的结果表明，门牙再生和牙齿间充质干细胞的分化需要 SCFAs。微生物群及其代谢物应被视为组织更新和再生的重要因素。