Kinetics of circulating endothelial progenitor cells in mice with type II collagen arthritis.

OBJECTIVE

To examine the significance in arthritis of circulating endothelial progenitor cells (cEPCs) reportedly increasing in neovascularization.

METHODS

Arthritis was induced by immunizing DBA/1J mice with bovine type II collagen on day 0. Age-matched normal DBA/1J mice were used as controls. Blood was collected from these mice on days 7, 14, 21, 28, and 35. Peripheral blood CD45-, CD34+, Flk-1+, CD117+ cells were regarded as cEPCs (Flk-1=vascular endothelial growth factor receptor 2). The number of cEPCs per 100 CD45+ cells was calculated by four-color flow cytometry, and compared with the arthritis score.

RESULTS

Arthritis developed about 3 days after booster immunization (day 21). On days 7, 14, and 21, no difference in cEPCs/100 CD45+ cells was noted between the arthritis and control groups. On days 28 and 35, cEPCs/100 CD45+ cells in the arthritis group were significantly greater in number than those in the control group. cEPCs/100 CD45+ cells on day 28 were greater in number than those on day 35. On day 28, a correlation was found between cEPCs/100 CD45+ cells and arthritis score.

CONCLUSION

In mice with type II collagen-induced arthritis, an increase in cEPCs was associated with the onset of arthritis. The number of cEPCs was greater during the development and progression of arthritis than that at the time of its establishment, suggesting that cEPCs are involved in the pathogenesis of arthritis.