Angiopoietin-like protein 2 deficiency promotes periodontal inflammation and alveolar bone loss.

BACKGROUND: Human periodontitis is a highly prevalent inflammatory disease that leads to connective tissue degradation, alveolar bone resorption, and tooth loss. Angiopoietin-like 2 (ANGPTL2) regulates chronic inflammation in various diseases and is functionally involved in maintaining tissue homeostasis and promoting tissue regeneration, but there is limited information about its function in periodontitis. Here we investigated the expression and explicit role of ANGPTL2 in periodontitis. METHODS: Immunohistochemistry and quantitative real-time PCR (qRT-PCR) were used to detect the ANGPTL2 expression in periodontal tissues and periodontal ligament cells (PDLCs). A ligature-induced periodontitis model was generated in wild-type and ANGPTL2 knockout mice. qRT-PCR and enzyme-linked immunosorbent assay were used to assess the production of inflammatory cytokines and matrix metalloproteinases (MMPs) in cultured PDLCs. Western blot was performed to detect proteins in relevant signaling pathways. RESULTS: Increased ANGPTL2 expression was observed in inflamed periodontal tissues and PDLCs. ANGPTL2 deficiency promoted alveolar bone loss with enhanced osteoclastogenesis and inflammatory reactions in ligature-induced periodontitis. Downregulation of ANGPTL2 remarkably enhanced expression levels of interleukin (IL)-6, IL-8, MMP1, and MMP13 in Porphyromonas gingivalis lipopolysaccharide-induced PDLCs, whereas ANGPTL2-overexpressing PDLCs showed opposite trends. ANGPTL2 downregulation activated STAT3 and nuclear factor-κB pathways and blocked Akt signaling under inflammatory environment. Treatment with a STAT3 inhibitor partially suppressed the inflammatory reaction of PDLCs mediated by ANGPTL2 knockdown. CONCLUSIONS: Our study provides the first evidence of an anti-inflammatory effect of ANGPTL2 in murine periodontitis. The findings demonstrate the critical and protective role of ANGPTL2 in alveolar bone loss and periodontal inflammation.