Angiopoietin-like 2 Upregulation Promotes Human Primary Chondrocyte Injury Via NF-κB And P38/MAPK Signaling Pathway

Background: Angiopoietin-like 2(ANGPTL2)is well known for its tissue remolding and pro-inflammation properties.However,the role of ANGPTL2 in osteoarthritis(OA)still remains unclear.The aim of this study was to explore the expression level of ANGPTL2 in human OA cartilage and investigate the function of ANGPTL2 in human chondrocytes injury.Methods: qRT-PCR,western blot and immunohistochemistry were employed to investigate the expression level of ANGPTL2 between human OA and normal cartilage samples.Next,human primary chondrocytes were treated with IL-1β to mimic OA progress in vitro,and the expression of ANGPTL2 were tested by q RT-PCR and western blot analysis.Furthermore,the effect of ANGPTL2 in the expression of pro-inflammation cytokines(IL-1β,IL-6)and proteolytic enzymes(MMP-1,MMP-13)in human primary chondrocyte were explored by gain-of-function and loss-of-function methods.At last,the nuclear factor kappa B(NF-κB)and p38/MAPK signaling pathways were activated by ANGPTL2 in IL-1β induced chondrocyte injury progress.Results: Firstly,the expression level of ANGPTL2 was elevated both in human OA cartilage samples and IL-1β stimulated human chondrocytes.Secondly,ANGPTL2 upregulation promotes extracellular matrix(ECM)degradation and inflammation mediator production in human chondrocytes.Finally,ANGPTL2 activated the NF-κB and p38/MAPK signaling pathways.Conclusion: This study,for the first time,highlight ANGPTL2 secreted by human chondrocytes plays a negative role in the pathogenesis of osteoarthritis,and it may be a potential therapeutic target in OA.