Increased scleraxis expression is associated with ligamentum flavum hypertrophy in patients with lumbar spinal canal stenosis.

Abstract

PURPOSE: To investigate the involvement of scleraxis in ligamentum flavum (LF) hypertrophy and fibrosis in patients with lumbar spinal canal stenosis (LSCS), with a particular focus on its relationship with myofibroblast accumulation. METHODS: LF samples were collected from 15 patients with LSCS and 7 control patients undergoing surgery for lumbar disc herniation or spinal tumor. LF thickness was measured on preoperative magnetic resonance imaging (MRI). Histological evaluation was performed with Gomori’s trichrome staining to quantify collagen fiber accumulation. Immunohistochemistry was used to detect α-smooth muscle actin (α-SMA) and scleraxis expressions, and positive cell ratios were compared between groups and layers (dorsal vs. ventral). Correlations between α-SMA and scleraxis expressions were analyzed. RESULTS: LF thickness was significantly greater in LSCS than in control. Histological analysis showed significantly increased collagen fiber accumulation in LSCS tissues, particularly in the dorsal layer. The proportion of α-SMA-positive myofibroblasts was significantly higher in LSCS tissues than in control tissue, and particularly enriched in the dorsal layer. Scleraxis expression was markedly elevated in LSCS tissues and colocalized with regions of collagen accumulation and α-SMA positivity. Significant positive correlations were observed between scleraxis and α-SMA expressions. CONCLUSION: The hypertrophied LF in LSCS patients exhibits increased collagen deposition, myofibroblast accumulation, and scleraxis expression, with strong correlations between scleraxis and α-SMA. These findings suggest that scleraxis contributes to the fibroblast-to-myofibroblast transition and fibrotic remodeling in LF, identifying it as a potential therapeutic target for LSCS.