Facet Joint Capsular Laxity in Degenerative Lumbar Spondylolisthesis Associated with the Increased Expression of Fractalkine (CX3CL1)/CX3CR1 Chemokine

Abstract

Introduction CX3CL1 and its receptor (CX3CR1) are part of a chemokine system involved in leukocyte recruitment and adhesion in chronic inflammatory disease. From previous study, the CX3CL1 and CX3CR1 activity has been investigated in ligamentum flavum, synovial membrane, and intervertebral discs, but not with the facet joint capsule-related issue. The purpose of this study is to investigate the following: (1) The role of fractalkine (CX3CL1)/CX3CR1 chemokine on facet joint capsular laxity in degenerative lumbar spondylolisthesis (DLS); (2) Correlation between expression of CX3CL1/CX3CR1 chemokine and degree of slippage by lumbar spondylolisthesis. Method The mRNA concentrations of CX3CL1/CX3CR1 chemokine were analyzed in the surgically obtained facet joint capsule specimens from grade 1 spondylolisthesis ( n = 12), grade 2 spondylolisthesis ( n = 12), and more than grade 3 spondylolisthesis ( n = 11) by real-time PCR. Grade 1 to 3 is being decided on degree of slippage which is, less than 5 mm, between 5 to 10 mm, and more than 10 mm. The localization of CX3CL1/CX3CR1 chemokine within the facet joint capsule was determined using immunohistochemical study. Plasma level of soluble fractalkine (sFKN) was measured by enzyme-linked immunosorbent assay (ELISA), respectively. Result The cells that shows higher CX3CL1/CX3CR1 chemokine expression ratio in the facet joint capsule are observed in tissues acquired from patients with higher degree of slippage by lumbar spondylolisthesis ( p = 0.000, 0.000). In ELISA, the plasma levels of sFKN was significantly higher in the group with more severe degree of slippage ( p = 0.002). There was greater CX3CL1/CX3CR1 expression in higher grade spondylolisthesis as quantified by RT–PCR ( p = 0.000, 0.003). Degree of slippage in patients with DLS were significantly correlated with serum CX3CL1 level ( R2 = 0.451, p = 0.000) and with mRNA expression of CX3CL1/CX3CR1 ( R2 = 0.360, p = 0.000) ( R2 = 0.205, p = 0.006). Conclusion This study identified for the first time that increases in CX3CL1 and CX3CR1 expressing cells are significantly related to facet joint capsular laxity, which may provide new conceptual and therapeutic approaches for treating spinal spondylolisthesis.