Department of Prosthodontics, Peking University School and Hospital of Stomatology, 22 Zhongguancun South Avenue, Haidian District, Beijing, 100081, China.
National Engineering Lab for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing, 100081, China.
Stem Cell Res Ther. 2019 Feb 13;10(1):57. doi: 10.1186/s13287-019-1167-3.
Tissue inflammation is an important problem in the field of human adipose-derived stem cell (ASC)-based therapeutic bone regeneration. Many studies indicate that inflammatory cytokines are disadvantageous for osteogenic differentiation and bone formation. Therefore, overcoming inflammation would be greatly beneficial in promoting ASC-mediated bone regeneration. The present study aims to investigate the potential anti-inflammatory role of Prostaglandin G/H synthase 1 (PTGS1) during the osteogenic differentiation of ASCs.
We performed TNFα treatment to investigate the response of PTGS1 to inflammation. Loss- and gain-of-function experiments were applied to investigate the function of PTGS1 in the osteogenic differentiation of ASCs ex vivo and in vivo. Western blot and confocal analyses were used to determine the molecular mechanism of PTGS1-regulated osteogenic differentiation.
Our work demonstrates that PTGS1 expression is significantly increased upon inflammatory cytokine treatment. Both ex vivo and in vivo studies indicate that PTGS1 is required for the osteogenic differentiation of ASCs. Mechanistically, we show that PTGS1 regulates osteogenesis of ASCs via modulating the NF-κB signaling pathway.
Collectively, this work confirms that the PTGS1-NF-κB signaling pathway is a novel molecular target for ASC-mediated regenerative medicine.
组织炎症是人类脂肪来源干细胞（ASC）治疗性骨再生领域的一个重要问题。许多研究表明，炎症细胞因子不利于成骨分化和骨形成。因此，克服炎症将极大地有利于促进 ASC 介导的骨再生。本研究旨在探讨前列腺素 G/H 合酶 1（PTGS1）在 ASC 成骨分化过程中的潜在抗炎作用。
我们进行 TNFα 处理以研究 PTGS1 对炎症的反应。采用缺失和功能获得实验研究 PTGS1 在 ASC 体外和体内成骨分化中的作用。采用 Western blot 和共聚焦分析来确定 PTGS1 调节成骨分化的分子机制。
我们的工作表明，PTGS1 的表达在炎症细胞因子处理后显著增加。体外和体内研究均表明，PTGS1 是 ASC 成骨分化所必需的。在机制上，我们表明 PTGS1 通过调节 NF-κB 信号通路来调节 ASC 的成骨作用。
综上所述，这项工作证实了 PTGS1-NF-κB 信号通路是 ASC 介导的再生医学的一个新的分子靶点。
