Liu Xuhong, Chen Tong, Wu Yuwei, Tang Zhihui
2nd Dental Center, School and Hospital of Stomatology, Peking University, Beijing, 100081, People's Republic of China; National Engineering Laboratory for Digital and Material Technology of Stomatology, School and Hospital of Stomatology, Peking University, Beijing, 100081, People's Republic of China.
2nd Dental Center, School and Hospital of Stomatology, Peking University, Beijing, 100081, People's Republic of China; National Engineering Laboratory for Digital and Material Technology of Stomatology, School and Hospital of Stomatology, Peking University, Beijing, 100081, People's Republic of China.
Biochem Biophys Res Commun. 2017 Jan 29;483(1):712-717. doi: 10.1016/j.bbrc.2016.12.076. Epub 2016 Dec 13.
Human bone marrow-derived stromal cells (hBMSC) are multi-potent stem cells that can differentiate into osteogenic and adipogenic lineages. Adiponectin (APN) is an adipocyte-derived hormone that modulates a series of metabolic processes. Recent studies revealed a relationship between APN and bone regeneration, though the underlying mechanism was not fully examined. Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a tumor suppressor and a therapeutic target for the metabolic syndrome. Its deletion mutants increase osteoblast activity and bone mineral density. Both APN and PTEN are involved in osteogenic differentiation. However, whether PTEN is involved in APN-induced bone metabolism remains unclear. This project was designed to study whether PTEN was involved in APN-mediated osteogenesis of hBMSCs. We found that APN downregulated PTEN expression and that both it and an inhibitor of PTEN (SF1670) increased the expression of osteogenic markers such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 in APN-treated hBMSCs. Our results suggested that APN enhanced osteogenic differentiation of hBMSCs in vitro partially by inhibiting PTEN expression. APN could be a therapeutic agent in tissue regeneration engineering and bone regeneration by inhibiting PTEN expression and then promoting the osteogenic differentiation of hBMSCs.
人骨髓间充质干细胞（hBMSC）是多能干细胞，可分化为成骨和成脂谱系。脂联素（APN）是一种脂肪细胞衍生的激素，可调节一系列代谢过程。最近的研究揭示了APN与骨再生之间的关系，但其潜在机制尚未完全研究清楚。第10号染色体上缺失的磷酸酶和张力蛋白同源物（PTEN）是一种肿瘤抑制因子，也是代谢综合征的治疗靶点。其缺失突变体可增加成骨细胞活性和骨矿物质密度。APN和PTEN均参与成骨分化。然而，PTEN是否参与APN诱导的骨代谢仍不清楚。本项目旨在研究PTEN是否参与APN介导的hBMSC成骨过程。我们发现APN下调PTEN表达，并且它和PTEN抑制剂（SF1670）均增加了APN处理的hBMSC中成骨标志物如骨钙素、碱性磷酸酶和 runt相关转录因子2的表达。我们的结果表明，APN通过抑制PTEN表达部分增强了体外hBMSC的成骨分化。通过抑制PTEN表达进而促进hBMSC的成骨分化，APN可能成为组织再生工程和骨再生中的一种治疗剂。
