Role of CCL4 and CCR5 during osteoclastogenesis of murine bone marrow-derived monocytes

Abstract

Chemokine CCL4 (MIP-1β) is released from osteoblast cells to restore the homeostasis of hematopoietic stem cells during the activation of bone marrow. In this study, the function of CCL4 during osteoclastogenesis was investigated. CCL4 promoted the migration and viability of pre-osteoclast cells. However, CCL4 had no direct effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in mouse pre-osteoclast cells. During osteoclastogenesis, the expression of CCR5, the CCL4 receptor, was rapidly reduced by RANKL treatment. CCR5 down-regulation by RANKL was mediated by MEK and JNK in pre-osteoclast cells and played a role in osteoclastogenesis. These results suggest that the chemoattractant effect and viability of CCL4 is involved in recruiting pre-osteoclasts but is diminished later its effect on osteoclastogenesis by the reduction of CCR5 when RANKL is prevalent.