Li Le, Wang Haiyan, Yu Dianqin, Wang Yantong, Zhao Yingchu, Yang Haoqing, Cao Yangyang, Cao Yu
Department of Stomatology, Tsinghua University Hospital, Beijing, 100084, China.
Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Tian Tan Xi Li No.4, Beijing, 100050, People's Republic of China.
Cell Tissue Bank. 2023 Mar;24(1):231-239. doi: 10.1007/s10561-022-10030-8. Epub 2022 Aug 8.
Evidences have showed stem cell mediated tissue regeneration is a promising method for the treatment of periodontitis. Insulin-like growth factor binding proteins-5 (IGFBP5) is a member of the insulin growth factor (IGFs) family and plays a regulatory role in cell proliferation and differentiation. Our previous study showed that IGFBP5 can promote osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and enhance periodontal tissue regeneration mediated by PDLSCs. However, the function of IGFBP5 in the process of PDLSCs senescence remains unclear. The present study showed IGFBP5 mRNA level was highly expressed in passage-induced aged PDLSCs cells. IGFBP5 knockdown decreased the ratio of senescence associated β-galactosidase (SA-β-Gal) positive cells, enhanced the activity of TERT, and down-regulated the expression levels of P16, P21, P53 mRNA and protein. Overexpression of IGFBP5 increased the ratio of SA-β-Gal positive staining PDLSCs, decreased the activity of telomerase TERT, and up-regulated the expression levels of P16, P21, P53 mRNA and protein related to PDLSCs senescence. In conclusion, IGFBP5 can accelerate the senescence of PDLSCs, indicating the potential target for maintaining the "young state" of stem cells.
有证据表明,干细胞介导的组织再生是治疗牙周炎的一种有前景的方法。胰岛素样生长因子结合蛋白5(IGFBP5)是胰岛素生长因子(IGFs)家族的一员,在细胞增殖和分化中起调节作用。我们之前的研究表明,IGFBP5可以促进牙周膜干细胞(PDLSCs)的成骨分化,并增强PDLSCs介导的牙周组织再生。然而,IGFBP5在PDLSCs衰老过程中的作用仍不清楚。本研究表明,IGFBP5 mRNA水平在传代诱导的衰老PDLSCs细胞中高表达。IGFBP5基因敲低降低了衰老相关β-半乳糖苷酶(SA-β-Gal)阳性细胞的比例,增强了端粒酶逆转录酶(TERT)的活性,并下调了P16、P21、P53 mRNA和蛋白的表达水平。IGFBP5的过表达增加了SA-β-Gal阳性染色的PDLSCs的比例,降低了端粒酶TERT的活性,并上调了与PDLSCs衰老相关的P16、P21、P53 mRNA和蛋白的表达水平。总之,IGFBP5可以加速PDLSCs的衰老,提示其可能是维持干细胞“年轻状态”的潜在靶点。