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Rutin is one of the flavonoids found in fruits and vegetables. Recent reports have revealed that rutin is a major player in proliferation and bone development. However, data on how rutin regulates the proliferation of periodontal ligament stem cells (PDLSCs), as well as the differentiation of osteogenic cells are scanty. Here, our findings showed that rutin enhanced PDLSCs proliferation, increased ALP activity, and matrix mineralization. Moreover, rutin significantly promoted the expression of osteogenic genes and elevated phosphorylated AKT and mTOR. Treatment with LY294002 reversed these effects by inhibiting PI3K. We also found that the expression levels of GPR30 were increased by rutin. Interestingly, this upregulation was not altered after the addition of LY294002. In addition, G15, a selective antagonist of GPR30, could reduce the beneficial effects induced by rutin and interfere with the modulation of PI3K/AKT/mTOR signal transduction. Collectively, our findings revealed that rutin increased proliferation and osteogenic differentiation of PDLSCs through GPR30-mediated PI3K/AKT/mTOR signal transduction. Therefore, it could be deduced that rutin as a certain flavonoid possesses therapeutic value for periodontal bone regeneration and tissue engineering. Impact statement In our study, the effects and mechanisms of rutin on the osteogenic differentiation and proliferation of PDLSCs were investigated. Our findings might provide basic knowledge and guidance to understand and use rutin in the bioengineering of the periodontal tissues and regeneration of bones. The following is a short description of the main findings: rutin promotes the osteogenic differentiation and proliferation of PDLSCs; PI3K/AKT/mTOR signal pathway mediates the effects of rutin on PDLSCs; rutin activates PI3K/AKT/mTOR signal pathway via GPR30.

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