Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/ß­catenin pathway.

ABSTRACT

Ankylosing spondylitis (AS) is an autoimmune condition characterized by chronic inflammation and abnormal ossification as the primary features of the disease. The aim of the present study was to investigate the role of C­X­C chemokine receptor type 4 (CXCR4) in ossification from patients with AS. CXCR4 expression was assessed by western blot analysis and immunohistochemistry analysis of tissues obtained from patients with AS and controls. Fibroblasts were isolated, cultured and incubated with AMD 3100 and stromal cell­derived factor­1 to inhibit and promote CXCR4 levels, respectively. CXCR4 was upregulated in hip synovial tissues from patients with AS compared with that observed in controls. AS fibroblasts exhibited increased proliferation and growth rates. Inhibition of CXCR4 increased the phosphorylation of ß­catenin and downregulated the expression of ß­catenin, v­myc avian myelocytomatosis viral oncogene homolog, cyclin D1 and osteocalcin. Alizarin red staining demonstrated a decrease in biomineralization activity following the inhibition of CXCR4. These data support the hypothesis that inhibiting CXCR4 in patients with AS may suppress the ossification of fibroblasts.