Bone erosion is associated with reduction of circulating endothelial progenitor cells and endothelial dysfunction in rheumatoid arthritis

Objective To identify factors influencing endothelial progenitor cell (EPC) counts in patients with rheumatoid arthritis (RA). Methods The number of circulating CD34+/vascular endothelial growth factor receptor 2-positive EPCs was measured in 126 RA patients and 46 non-RA control patients. Endothelial function was assessed by brachial flow-mediated dilation (FMD). Serum CXCL12 concentrations were determined using an enzyme-linked immunosorbent assay. EPCs and FMD were measured at baseline and after 24 weeks of anti-tumor necrosis factor α (TNFα) therapy in 29 patients with active RA. Results The numbers of circulating EPCs were significantly lower in the RA patients than in the non-RA controls. In multivariate analysis, older age, reduced levels of high-density lipoprotein cholesterol, and higher bone erosion scores were independent risk factors for reduced EPC counts in RA patients. Serum CXCL12 levels correlated negatively with EPC counts, but positively with bone erosion scores. FMD was impaired in RA patients, and a decreased FMD in RA was closely associated with a higher bone erosion score and a reduced EPC count. In addition, EPC counts were restored by anti-TNFα therapy, and this increase was paralleled by improvement in FMD. Interestingly, restoration of EPC counts was attenuated in patients with higher bone erosion scores than in those with lower scores, despite similar levels of improvement in disease activity. Conclusion The numbers of circulating EPCs in RA patients are reduced and are inversely correlated with serum levels of CXCL12. Reduced EPC counts are closely associated not only with bone erosion, but also with endothelial dysfunction.