Progranulin Reverses Decitabine-Induced Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Through Downregulation of NF-kappa B Signaling Pathway

摘要

Decitabine can induce BMSCs adipogenic differentiation. Progranulin (PGRN) is a chondrogenic factor. However, the effect of Progranulin on the adipogenic differentiation of BMSCs induced by decitabine remains unclear. Rat BMSCs were isolated and divided into control group, Decitabine group, and Decitabine + PGRN group followed by analysis of survival rate of BMSCs cells by MTT assay, Caspase 3 activity, ALP activity, Runx2, OP and PPAR gamma 2 expression by Real time PCR, lipids formation by Oil red O staining and the expression of NF-kappa B by Western blot. Decitabine treatment can significantly inhibit the proliferation of BMSCs, promote the increase of Caspase 3 activity, decrease ALP activity and the expression of Runx2 and OP, increase PPAR gamma 2 expression, the ability of adipogenesis and NF-SB expression (P < 0005). Progranulin addition significantly promoted BMSCs proliferation, inhibited Caspase 3 activity, increased ALP activity and Runx2, OP expression, decreased PPAR gamma 2 expression, adipogenic capacity and NF-kappa B expression, compared to Decitabine group (P < 0005). Decitabine inhibits BMSCs proliferation, promotes apoptosis, induces adipogenic differentiation, and inhibits osteogenic differentiation. Progranulin reverses the effect of defercitin on the induction of adipogenic differentiation of BMSCs by down-regulating the NF-kappa B signaling pathway.