Downregulation of angiopoietin-like protein 2 inhibits cementoblast differentiation partially by activating the ERK1/2 signaling pathway
Downregulation of angiopoietin-like protein 2 inhibits cementoblast differentiation partially by activating the ERK1/2 signaling pathway
复制标题
血管生成素样蛋白 2 的下调部分通过激活 ERK1/2 信号通路抑制成牙骨质细胞分化
DOI：
--
复制
发表时间：
2019
影响因子：
2.2
通讯作者：
Cao Zhengguo
中科院分区：
文献类型：
--
作者：
Jiang Chenxi;Liu Huan;Sun Hualing;Wang Xiaoxuan;Liao Haiqing;Ma Li;Cao Zhengguo
血管生成素样蛋白2(Angiopoietin-like Protein 2，ANGPTL2)在脂肪组织中大量表达，与组织动态平衡有关，促进成骨细胞和软骨细胞分化。在牙齿中，牙骨质是一层薄薄的矿化组织，由成牙骨质细胞形成，覆盖整个牙根表面，是牙周组织的重要组成部分。成牙骨质细胞调控牙骨质基质的沉积和矿化。然而，ANGPTL2对成牙骨质细胞分化的影响还没有研究。本研究的目的是阐明ANGPTL2在成牙骨质细胞分化过程中的作用，并确定其可能的机制。结果表明，在成牙骨质细胞分化过程中，ANGPTL2的表达水平逐渐升高。用短发夹状RNA敲除ANGPTL2后，成骨标记物OSX、碱性磷酸酶(ALP)、骨涎蛋白(BSP)和骨钙素(OCN)水平降低。此外，ALP活性和钙化结节数目较阴性对照组显著减少。有趣的是，ERK1/2信号通路在ANGPTL2基因敲除后被激活。ERK1/2信号通路抑制剂PD98059可部分挽救ANGPTL2下调所致的成牙本质细胞分化能力下降。总的来说，ANGPTL2基因敲除部分通过激活ERK1/2信号通路抑制成牙本质细胞的分化。这些结果表明，ANGPTL2在成牙骨质细胞分化过程中是不可或缺的。
Angiopoietin-like protein 2 (ANGPTL2) is abundantly expressed in adipose tissue, is associated with tissue homeostasis, and promotes osteoblast and chondrocyte differentiation. In teeth, cementum, a thin layer of mineralized tissue that is formed by cementoblasts, covers the entire root surface and is a vital component of periodontium. The cementoblasts regulate the deposition and mineralization of the cementum matrix. However, the effects of ANGPTL2 on cementoblast differentiation have not been studied. The objective of this study was to elucidate the role of ANGPTL2 during cementoblast differentiation and determine its underlying mechanisms. Our results showed that the expression levels of ANGPTL2 gradually increased during cementoblast differentiation. After ANGPTL2 was knocked down using short-hairpin RNA, the levels of the osteogenic markers osterix (OSX), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN) decreased. In addition, ALP activity and the number of calcified nodules were dramatically reduced compared with those in the negative control. Interestingly, the ERK1/2 signaling pathway was activated after ANGPTL2 knockdown. Treatment with PD98059, the inhibitor of the ERK1/2 signaling pathway, partially rescued the decreased differentiation capability of cementoblast caused by ANGPTL2 downregulation. Collectively, ANGPTL2 knockdown inhibited cementoblast differentiation partially by activating the ERK1/2 signaling pathway. These findings suggest that ANGPTL2 was indispensable in cementoblast differentiation.