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Updated: Sep 3, 2025

Laminectomy for the Removal of Thoracic Ossification of the Ligamentum Flavum TOLF Using Ultrasonic and Conventional Osteotomes
Published on: April 21, 2023
Macrophage migration inhibitory factor takes part in the lumbar ligamentum flavum hypertrophy
Qi-Lin Lu1, Zi-Xuan Zheng2, Yu-Hui Ye2
1Department of Orthopaedics, General Hospital of Central Theater Command, Wuhan, Hubei 430070, P.R. China.
Abstract:
The present study aimed to observe the content difference of macrophage migration inhibitory factor [MIF; novoprotein recombinant human MIF (n‑6his) (ch33)], TGFβ1 and MMP13 in patients with and without ligamentum flavum (LF) hypertrophy and investigate the roles of MIF in LF hypertrophy. The concentration of MIF, TGFβ1 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 TGFβ1, MMP13, type I collagen (COL‑1) and type III collagen (COL‑3) and Src which were promoted by MIF. The concentration of MIF, TGFβ1 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 TGFβ1, 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.
Insights
Macrophage migration inhibitory factor (MIF) drives ligamentum flavum hypertrophy by promoting cell proliferation and extracellular matrix changes via the Src kinase pathway. Elevated MIF levels are linked to lumbar spinal stenosis.
Area of Science:
- Spinal Surgery
- Biochemistry
- Cell Biology
Background:
- Ligamentum flavum (LF) hypertrophy is a significant cause of lumbar spinal stenosis (LSS).
- The role of macrophage migration inhibitory factor (MIF) in LF hypertrophy requires further elucidation.
Purpose of the Study:
- To compare MIF, TGFβ1, and MMP13 levels in patients with and without LF hypertrophy.
- To investigate the specific mechanisms by which MIF influences LF hypertrophy.
Main Methods:
- ELISA to quantify MIF, TGFβ1, and MMP13 in LF tissues from LSS and lumbar disc herniation (LDH) groups.
- Primary LF cell culture, CCK-8 assay, Western blot, and quantitative PCR to assess MIF's effects on cell proliferation and gene/protein expression (TGFβ1, MMP13, COL-1, COL-3, Src).
Main Results:
- MIF, TGFβ1, and MMP13 concentrations were significantly higher in the LSS group compared to the LDH group.
- MIF treatment (40 nM, 48 h) significantly increased LF proliferation (P<0.05).
- MIF upregulated the expression of TGFβ1, MMP13, COL-1, COL-3, and Src, effects inhibited by a Src inhibitor (PP1).
Conclusions:
- MIF promotes LF proliferation and extracellular matrix remodeling, likely through the Src kinase signaling pathway.
- MIF and its associated inflammatory responses are key contributors to LF hypertrophy, offering potential therapeutic targets.
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