Increased advanced glycation end products in hypertrophied ligamentum flavum of diabetes mellitus patients.

Ligamentum flavum (LF) hypertrophy plays a dominant role in lumbar spinal stenosis (LSS). Although LSS prevalence is known to be higher in patients with diabetes mellitus (DM), the underlying pathomechanisms are not well understood. Abnormal advanced glycation end products (AGEs) formation occurs in DM and promotes tissue damage in various organs through degeneration and inflammation. To analyze and compare LF histology focused on AGE status between control patients, LSS patients with DM, and LSS patients without DM. Basic research study design utilizing human LF tissue for histologic analyses. LF tissue samples were collected from patients who underwent lumber decompression surgery for LSS in the author's institution. Quantitative visualization of Masson's Trichrome (MT) stains, and AGE immunohistochemistry (IHC) for the three groups. Ten LF specimens from LSS patients with DM (DM group, mean age 71.4 years), 10 from LSS patients without DM (non-DM group, mean age 71.2 years), and 9 from patients with lumbar disc herniation or cauda equina tumor (control group, mean age 49.0 years) were harvested during surgery and histologically analyzed. Percentage of elastic fiber areas (%EF) was measured with MT staining, and the percentage of AGE immuno-positive areas (%AGEs) was measured with IHC. The average %EFs were 12.8 in the DM group, 17.1 in the non-DM group, and 24.9 in the control group. The decrease in the elastic fibers was significantly more in the DM group than in the non-DM (p<.01) and control groups (p<.001). Accumulation of AGEs was found mainly in the extracellular matrix in areas of elastic fiber disruption. The %AGEs were 18.3 in the DM group, 12.1 in the non-DM group, and 4.6 in the control group. These were significantly larger in the DM group than in the non-DM (p<.01) and control (p<.01) groups. The %AGEs also positively correlated with patient age (p<.01, R=0.47). Accumulation of AGEs is significantly greater in the LF of DM patients and correlates with patient age. AGEs may accelerate degeneration and hypertrophy of LF with age and may lead to higher prevalence of LSS in patients with DM. The present results partly reveal the molecular mechanism of LF hypertrophy, suggesting that AGEs may be involved in the process of LF degeneration in the elderly and patients with DM.

Maruf MH ，Suzuki A ，Hayashi K ，Habibi H ，Salimi H ，Terai H ，Tamai K ，Hoshino M ，Toyoda H ，Yamada K ，Takahashi S ，Ohyama S ，Hori Y ，Nakamura H ... -  《-》

Matrix metalloproteinase 13 in the ligamentum flavum from lumbar spinal canal stenosis patients with and without diabetes mellitus.

Cui G ，Watanabe K ，Miyauchi Y ，Hosogane N ，Tsuji T ，Ishii K ，Nakamura M ，Toyama Y ，Chiba K ，Miyamoto T ，Matsumoto M ... -  《-》

Is platelet-derived growth factor-BB expression proportional to fibrosis in the hypertrophied lumber ligamentum flavum?

Zhang Y ，Chen J ，Zhong ZM ，Yang D ，Zhu Q ... -  《-》

Hypertrophy of ligamentum flavum in lumbar spine stenosis associated with the increased expression of connective tissue growth factor.

Hypertrophy of the ligamentum flavum (LF) contributes to lumbar spinal stenosis (LSS), and results mainly from fibrosis. Connective tissue growth factor (CTGF) is a profibrotic factor involved in the fibrotic process. This study aimed to evaluate CTGF expression in hypertrophied lumbar LF and the involvement of CTGF in LF hypertrophy. Ten patients with LSS were enrolled in this study. The control group included 10 patients with lumbar disc herniation. LF thickness was measured on the preoperative axial T1-weighted MRI. LF samples were collected during surgery. LF fibrosis was scored by Masson's trichrome staining. CTGF expression was determined by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. Correlation between LF thickness and CTGF expression was analyzed. Human LF cells were cultured and treated with recombinant human (rh) CTGF. Expression of types I and III collagen was determined by real-time PCR and ELISA. The thickness and fibrosis scores of LF in the LSS group were higher than that in the control group (all P < 0.001). CTGF was expressed in the extracellular matrix of all ligament samples, and was significantly higher in the LSS group than that in the control group (P < 0.001). The increase of CTGF expression was positive correlation with the LF thickness (r = 0.969, P = 0.000). rhCTGF treatment increased the mRNA expression and protein synthesis of types I and III collagen of the LF cells (all P < 0.001). Our results suggest that the increased expression of CTGF is associated with hypertrophy of the LF in patients with LSS.

Zhong ZM ，Zha DS ，Xiao WD ，Wu SH ，Wu Q ，Zhang Y ，Liu FQ ，Chen JT ... -  《-》

The expression of P16 and S100 associated with elastin degradation and fibrosis of the Ligamentum Flavum hypertrophy.

Hu W ，Kan S ，Liu G ，Cao Z ，Zhu R ... -  《BMC MUSCULOSKELETAL DISORDERS》