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Cell Death Dis. 2018 May 1;9(5):495. doi: 10.1038/s41419-018-0562-5.

CCL4 enhances preosteoclast migration and its receptor CCR5 downregulation by RANKL promotes osteoclastogenesis.

Author information

1
Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
2
Department of Biochemistry, BK21 PLUS Program for Creative Veterinary Science Research and Research Institute for Veterinary Science, College of Veterinary Medicine, Seoul National University, Seoul, South Korea. jeycho@snu.ac.kr.

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, we investigated the function of CCL4 and its receptor CCR5 during osteoclastogenesis. CCL4 promoted the migration and viability of preosteoclast cells. However, CCL4 had no direct effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in mouse preosteoclast cells. In addition, CCR5 expression was rapidly reduced by RANKL treatment, which was recovered by IFN-γ during osteoclastogenesis. CCR5 downregulation by RANKL was mediated by MEK and JNK in preosteoclast cells and promoted osteoclastogenesis. These results suggest that CCL4 can enhance the recruitment of preosteoclasts to bone in the early stage, and the reduction of CCR5 promotes osteoclastogenesis when RANKL is prevalent.

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