MCP-5 suppresses osteoclast differentiation through Ccr5 upregulation

J Cell Physiol. 2024 Feb;239(2):e31171. doi: 10.1002/jcp.31171. Epub 2024 Jan 12.

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.

Keywords: Ccr5; JNK; MCP-5; NF-κB; osteoclast.

MeSH terms

  • Animals
  • Cell Differentiation* / physiology
  • Cells, Cultured
  • Humans
  • Male
  • Membrane Glycoproteins* / metabolism
  • Mice
  • Mice, Inbred ICR
  • Monocyte Chemoattractant Proteins / genetics
  • Monocyte Chemoattractant Proteins / metabolism
  • Monocyte Chemoattractant Proteins / pharmacology
  • NF-kappa B / metabolism
  • Osteoclasts* / cytology
  • Osteoclasts* / metabolism
  • RANK Ligand / metabolism
  • RANK Ligand / pharmacology
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • Up-Regulation

Substances

  • Membrane Glycoproteins
  • NF-kappa B
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Monocyte Chemoattractant Proteins
  • CCR5 protein, mouse