Periodontal ligament stem cells (PDLSCs) plays an important role in tissue engineering. As the age increased, the cell viability and osteogenic differentiation of PDLSCs all decreased. Low density lipoprotein receptor related protein 5 (LRP5) was found to promote bone marrow mesenchymal stem cells osteogenic differentiation. Therefore, our study explored the effect of LRP5 on normal and aged PDLSCs and relative mechanism. Here, we found that the expression of LRP5 in PDLSCs of 24 week-old mice was decreased compared with PDLSCs of 5 week-old mice (n = 5). . LRP5 overexpression in PDLSCs increased the intensity of alkaline phosphatase and alizarin red staining, accompanied with upregulated the levels of RUNX family transcription factor 2, collagen type I, and β-Catenin. LRP5 knockdown displayed the opposite results in PDLSCs in vitro. LRP5 overexpression in aged PDLSCs restored part ability of osteogenic differentiation. Meantime, LRP5 increased the protein expression of phosphorylation of mammalian target of rapamycin (p-mTOR) in normal and aged PDLSCs. Immunofluorescence showed that LRP5 increased the accumulation of p-mTOR nucleus. The effect of LRP5 in promoting osteogenic differentiation of PDLSCs can be antagonized by mTOR inhibitor rapamycin. These findings suggest that LRP5 positively regulate osteogenic differentiation of normal and aged PDLSCs and may be a potential target for enlarging the application of PDLSCs in tissue regeneration.

牙周膜干细胞（PDLSCs）在组织工程中发挥着重要作用。随着年龄的增长，PDLSCs的细胞活力和成骨分化均下降。发现低密度脂蛋白受体相关蛋白 5 (LRP5) 可促进骨髓间充质干细胞成骨分化。因此，我们的研究探讨了LRP5对正常和老年PDLSCs的影响及相关机制。在这里，我们发现与 5 周龄小鼠的 PDLSCs 相比，24 周龄小鼠的 PDLSCs 中 LRP5 的表达降低（n = 5）。.PDLSCs 中 LRP5 过表达增加了碱性磷酸酶和茜素红染色的强度，同时上调了 RUNX 家族转录因子 2、I 型胶原蛋白和 β-Catenin 的水平。LRP5 敲低在体外 PDLSC 中显示出相反的结果。LRP5 在老年 PDLSC 中的过表达恢复了成骨分化的部分能力。同时，LRP5增加了正常和老年PDLSC中哺乳动物雷帕霉素靶蛋白（p-mTOR）的磷酸化蛋白表达。免疫荧光显示LRP5增加了p-mTOR核的积累。LRP5促进PDLSCs成骨分化的作用可以被mTOR抑制剂雷帕霉素拮抗。