Dental Stem Cell Biology Research Unit and Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand.
Centre de Recherche des Cordeliers, Universite de Paris, Sorbonne Universite, Paris, France.
Oral Dis. 2023 Mar;29(2):735-746. doi: 10.1111/odi.14030. Epub 2021 Oct 7.
To investigate the role of phosphatase and tensin homolog (PTEN) in dental pulp cells (hDPs) and adipose-derived mesenchymal stem cells (hADSCs).
Genetic variant was identified with exome sequencing. The hDPs isolated from a patient with Cowden syndrome were investigated for their proliferation, osteogenesis, adipogenesis, and gene expression compared with controls. The normal hDPs and hADSCs were treated with the PTEN inhibitor, VO-OHpic trihydrate (VOT), to investigate the effect of PTEN inhibition.
A heterozygous nonsense PTEN variant, c.289C>T (p.Gln97*), was identified in the Cowden patient's blood and intraoral lipomas. The mutated hDPs showed significantly decreased proliferation, but significantly upregulated RUNX2 and OSX expression and mineralization, indicating enhanced osteogenic ability in mutated cells. The normal hDPs treated with VOT showed the decreases in proliferation, colony formation, osteogenic marker genes, alkaline phosphatase activity, and mineral deposition, suggesting that PTEN inhibition diminishes proliferation and osteogenic potential of hDPs. Regarding adipogenesis, the VOT-treated hADSCs showed a reduced number of cells containing lipid droplets, suggesting that PTEN inhibition might compromise adipogenic ability of hADSCs.
PTEN regulates proliferation, enhances osteogenesis of hDPs, and induces adipogenesis of hADSCs. The gain-of-function PTEN variant, p.Gln97*, enhances osteogenic ability of PTEN in hDPs.
研究磷酸酶和张力蛋白同源物（PTEN）在牙髓细胞（hDPs）和脂肪来源间充质干细胞（hADSCs）中的作用。
通过外显子组测序鉴定遗传变异。与对照组相比，对从患有考登综合征的患者中分离出的 hDPs 进行增殖、成骨、成脂和基因表达研究。用 PTEN 抑制剂 VO-OHpic 三水合物（VOT）处理正常 hDPs 和 hADSCs，以研究 PTEN 抑制的作用。
在考登患者的血液和口腔内脂肪瘤中发现了杂合的无意义 PTEN 变体 c.289C>T（p.Gln97*）。突变的 hDPs 显示增殖明显减少，但 RUNX2 和 OSX 表达和矿化明显上调，表明突变细胞的成骨能力增强。用 VOT 处理的正常 hDPs 显示增殖、集落形成、成骨标志物基因、碱性磷酸酶活性和矿化沉积减少，表明 PTEN 抑制降低了 hDPs 的增殖和成骨潜能。关于成脂，VOT 处理的 hADSCs 显示含有脂滴的细胞数量减少，表明 PTEN 抑制可能损害 hADSCs 的成脂能力。
PTEN 调节增殖，增强 hDPs 的成骨能力，并诱导 hADSCs 的成脂能力。获得功能的 PTEN 变体 p.Gln97*增强了 hDPs 中 PTEN 的成骨能力。
