Progranulin Protects Chondrocytes Induced by Lipopolysaccharide via Regulating the Focal Adhesion Kinase (FAK)/Mitogen-Activated Protein Kinase (MAPK) Pathway

Osteoarthritis (OA) is frequently associated with loss of articular cartilage and is more common in elderly patients. Progranulin (PGRN) is a chondrogenic factor. However, the role of PGRN in inflammatory articular chondrocyte arthritis and related mechanisms has not been elucidated. In vitro cultured chondrocytes were divided into control group, LPS group that was treated with 1 mu g/ml lipopolysaccharide (LPS), and PGRN group, in which LPS-stimulated chondrocytes were treated with PGRN (5 mu M and 10 mu M). The survival rate of chondrocytes was detected by tetrazolium salt colorimetry (MU method). MMP-3, tissue metalloproteinase inhibitor 1 (TIMP-1), and MMP3/TIMP-1 ratio were assessed by Western blot. The expressions of FAK and MAPK were detected by Western blot. TNF-alpha and IL-1 beta secretion was evaluated by ELISA. Chondrocyte survival rate was decreased, Caspase 3 activity increased, MMP-3 expression upregulated, TIMP-1 expression reduced, MMP-3/TIMP-1 ratio elevated, FAK and MAPK expressions downregulated, and TNF-alpha and IL-1 beta secretions enhanced in LPS group (P < 0.05). PGRN significantly promoted the survival of LPS-treated chondrocytes, attenuated Caspase 3 activity, decreased MMP-3 level, enhanced TIMP-1 level, decreased MMP-3/TIMP-1 ratio, upregulated FAK and MAPK, and inhibited TNF-alpha and IL-1 beta secretions dose dependently (P <0.05). PGRN can reduce the apoptosis of osteoarthritic chondrocytes, promote cell proliferation, reduce secretion of inflammatory factors, and delay the progression of osteoarthritis possibly through regulating FAK/MAPK pathway.