Macrophage migration inhibitory factor takes part in the lumbar ligamentum flavum hypertrophy

The present study aimed to observe the content difference of macrophage migration inhibitory factor [MIF; novoprotein recombinant human MIF (n-6his) (ch33)], TGF beta 1 and MMP13 in patients with and without ligamentum flavum (LF) hypertrophy and investigate the roles of MIF in LF hypertrophy. The concentration of MIF, TGF beta 1 and MMP13 in LF were detected by ELISA in a lumbar spinal stenosis (LSS) group and a lumbar disc herniation (LDH) group. Culture of primary LFs and identification were performed for the subsequent study. Cell treatments and cell proliferation assay by CCK-8 was performed. Western blot and quantitative PCR analysis were used to detect the expression of TGF beta 1, MMP13, type I collagen (COL-1) and type III collagen (COL-3) and Src which were promoted by MIF. The concentration of MIF, TGF beta 1 and MMP13 were higher in the LSS group compared with the LDH group. Culture of primary LFs and identification were performed. Significant difference in LFs proliferation occurred with treatment by MIF at a concentration of 40 nM for 48 h (P<0.05). The gene and protein expression of TGF beta 1, MMP13, COL-1, COL-3 and Src were promoted by MIF (P<0.05). Proliferation of LFs was induced by MIF and MIF-induced proliferation of LFs was inhibited by PP1 (a Src inhibitor). MIF may promote the proliferation of LFs through the Src kinase signaling pathway and can promote extracellular matrix changes by its pro-inflammatory effect. MIF and its mediated inflammatory reaction are driving factors of LF hypertrophy.