Transforming Growth Factor Beta/Smad Pathway Participates In Lumbar Ligamentum Flavum Hypertrophy

Aims: Hypertrophy of ligamentum flavum (LF) contributes to lumbar spinal stenosis (LSS) and is caused mainly by fibrosis. This study aimed to investigate the involvement of TGF beta/Smad pathway in human lumbar LF hypertrophy. Methods: Six patients with LSS were enrolled in this study. The control group included six patients with lumbar disc herniation (LDH). LF samples were collected during surgery for immunohistochemistry, real-time PCR and Western blot analysis. Human LF cells were cultured and treated with TGF beta 1, and type I collagen and Smad expression were detected. Results: Hypertrophic LF was characterized by a considerable distortion of the elastic matrix and fibrotic transformation by extracellular collagen deposition. Immunohistochemical analysis detected TGF beta 1, p-Smad 2/3, Smad 4 and Smad 7 in all LF samples. TGF beta 1, p-Smad 2/3 and Smad 4 levels were significantly higher in LSS group than in LDH group, while Smad 7 level was lower in LSS group than in LDH group. The levels of Smad 2, 3 and 4 were slightly upregulated 1 h after treatment with TGF beta 1. However, Smad 2/3 levels significantly decreased 24 h after TGF beta 1 treatment. In contrast, Smad 7 showed dynamic change: expression was markedly increased 1 h after TGF beta 1 stimulation but decreased at 24 h. The expression of type I collagen was increased at both 1 h and 24 h after TG beta 1 stimulation. Conclusion: During LF hypertrophy, the expression of TGF beta/Smad pathway components is changed. TGF beta/Smad pathway may contribute to LF hypertrophy.