Downregulation of angiopoietin-like protein 2 inhibits cementoblast differentiation partially by activating the ERK1/2 signaling pathway

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