MCP-5 suppresses osteoclast differentiation through Ccr5 upregulation |
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| Authors: | Jung Ha Kim Kabsun Kim Inyoung Kim Semun Seong Jeong-Tae Koh Nacksung Kim |
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| Institution: | 1. Department of Pharmacology, Chonnam National University Medical School, Gwangju, Republic of Korea;2. Hard-Tissue Biointerface Research Center, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea |
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| Abstract: | Human monocyte chemoattractant protein-1 (MCP-1) in mice has two orthologs, MCP-1 and MCP-5. MCP-1, which is highly expressed in osteoclasts rather than in osteoclast precursor cells, is an important factor in osteoclast differentiation. However, the roles of MCP-5 in osteoclasts are completely unknown. In this study, contrary to MCP-1, MCP-5 was downregulated during receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation and was considered an inhibitory factor in osteoclast differentiation. The inhibitory role of MCP-5 in osteoclast differentiation was closely related to the increase in Ccr5 expression and the inhibition of IκB degradation by RANKL. Transgenic mice expressing MCP-5 controlled by Mx-1 promoter exhibited an increased bone mass because of a decrease in osteoclasts. This result strongly supported that MCP-5 negatively regulated osteoclast differentiation. MCP-5 also prevented severe bone loss caused by RANKL. |
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| Keywords: | Ccr5 JNK MCP-5 NF-κB osteoclast |
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