Hypertrophy and Fibrosis of the Ligamentum Flavum in Lumbar Spinal Stenosis is Associated with Increased Expression of LPA and LPAR1.

STUDY DESIGN: Histological, immunohistochemical, and ELISA analysis of the human ligamentum flavum (LF).

OBJECTIVE: The purpose of this study was to determine the level of expression of LPA in the LF from LSS patients and to analyze the relationship among LPA, LPA receptors (LPARs) and LF hypertrophy.

SUMMARY OF BACKGROUND DATA: Ligamentum flavum (LF) hypertrophy and fibrosis are important causes of Lumbar spinal stenosis (LSS). Lysophosphatidic acid (LPA) is involved in the fibrotic process in multiple organ systems. Therefore, we hypothesized that LPA and its receptors might also play a role in degeneration of the LF in LSS patients.

METHODS: Forty-one LF samples were enrolled in this study. The thickness of the LF was measured by MRI. Histologic analysis using hematoxylin and eosin (H&E) and Masson's trichrome stain was performed for each LF to evaluate the architecture of the extracellular matrix (ECM). The content of LPA and CTGF in LF samples was analyzed using ELISA. The expression of LPAR1 was determined by immunohistochemistry.

RESULTS: Degeneration of the LF was characterized by an increase in disorganized elastic fibers and fibrotic transformation by extracellular collagen deposition. The thickness of the LF and the concentration of LPA and CTGF in the hypertrophic LF group were significantly higher than the control group. Furthermore, the LPA and CTGF concentrations had a positive correlation with the LF thickness (r=0.91, P<0.001 and r=0.943, P<0.001, respectively). Based on immunohistochemical analysis, the expression of LPAR1 was increased in the hypertrophy group.

CONCLUSIONS: The increased expression of LPA and LPAR1 is associated with the fibrosis and hypertrophy of the LF in patients with LSS. Further study on the mechanism underlying LF fibrosis may lead to new therapies for LF hypertrophy and fibrosis.