Progranulin Regulates the Differentiation of Bone Marrow Mesenchymal Stem Cells Under Inflammation Through Focal Adhesion Kinase (FAK)/Mitogen-Activated Protein Kinase (MAPK) Pathway

Abstract

Osteogenic differentiation of BMSCs is beneficial to the treatment of osteoarthritis. Progranulin (PGRN) is a chondrogenic factor. However, the role of progranulin in the differentiation of BMSCs under inflammation remains unclear. Rat BMSCs were isolated and divided into control group, inflammation group (treated with LPS), and PGRN group (5 and 10 /μM) followed by analysis of survival rate of BMSCs by MTT assay, Caspase 3 activity, ALP activity, expression of Runx2 and OP by real time PCR, level of MMP-3, TIMP-1, FAK and MAPK by Western blot and IL-6 and IL-10 secretion by ELISA. LPS treatment significantly inhibited BMSCs proliferation, increased Caspase 3 activity, decreased ALP activity, expression of Runx2 and OP, increased IL-6 secretion, decreased IL-10 secretion, increased MMP-3 expression, decreased expression of TIMP-1, FAK and p-P38 (P < 0.05). PGRN treatment on BMSCs under inflammation significantly promoted cell proliferation, decreased Caspase 3 activity, increased ALP activity, expression of Runx2 and OP, decreased IL-6 secretion, increased IL-10 secretion, decreased MMP-3 expression, and increased TIMP-1, FAK and p-P38 expression (P < 0.05) with more significant changes in the higher concentration. Under inflammation, BMSCs proliferation was inhibited, apoptosis was increased, and osteogenic differentiation was weakened. PGRN inhibits the proliferation of BMSCs and apoptosis, and promotes osteogenic differentiation by regulating FAK/MAPK pathway.