Abstract:
:Duffy antigen receptor for chemokines (DARC) binds to a number of pro-inflammatory chemokines, and since chemokines are known to regulate trafficking of osteoclast (OC) precursors, we predicted that DARC would regulate OC recruitment to sites of inflammation by modulating chemokine activity. To test this hypothesis, we evaluated the mRNA expression of Darc and the chemokines known to bind to DARC, in endothelial cells treated with bacterial lipopolysaccharide (LPS). The mRNA expression of Mcp-1, Rantes, Darc and Ccr5 was significantly increased in endothelial cells in response to LPS treatment. Blocking the function of DARC with neutralizing antibody partially abrogated the effect of LPS on the mRNA expression of Mcp-1 and Rantes. In vivo, mice with targeted disruption of Darc gene (Darc-KO) and control wild-type (WT) mice were used to assess the role of DARC in response to single LPS application on the top of parietal bones. Five hours post-LPS injection, local expression of Cd14 mRNA (a marker of inflammatory monocytes) was significantly increased in both lines of mice. However, the magnitude of increase was greater in WT mice compared with Darc-KO mice suggesting a role for DARC in mediating the recruitment of monocytes in response to LPS. Histological staining for tartrate-resistant acid phosphatase (TRAP) in calvaria sections taken from the injection sites revealed a significant reduction in TRAP-labeled surface per bone surface in response to LPS in Darc-KO mice compared with WT mice. Based on these findings, we concluded that DARC regulates recruitment of OC precursors at the inflammation site, probably through regulation of chemokines transcytosis across endothelial cell barrier.
journal_name
Calcif Tissue Intjournal_title
Calcified tissue internationalauthors
Alemi F,Elgendy M,Edderkaoui Bdoi
10.1007/s00223-016-0170-2subject
Has Abstractpub_date
2016-11-01 00:00:00pages
481-488issue
5eissn
0171-967Xissn
1432-0827pii
10.1007/s00223-016-0170-2journal_volume
99pub_type
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journal_title:Calcified tissue international
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journal_title:Calcified tissue international
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journal_title:Calcified tissue international
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journal_title:Calcified tissue international
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