MCP-5 suppresses osteoclast differentiation through Ccr5 upregulation.
Jung Ha KimKabsun KimInyoung KimSemun SeongJeong Tae KohNack-Sung KimPublished in: Journal of cellular physiology (2024)
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.
Keyphrases
- bone loss
- nuclear factor
- poor prognosis
- endothelial cells
- toll like receptor
- transcription factor
- signaling pathway
- type diabetes
- gene expression
- dna methylation
- cell proliferation
- regulatory t cells
- induced apoptosis
- long non coding rna
- metabolic syndrome
- endoplasmic reticulum stress
- early onset
- adipose tissue
- diabetic rats
- high fat diet induced