Dominant negative MCP-1 blocks human osteoclast differentiation

Morrison, Nigel A., Day, Christopher J. and Nicholson, Geoff C. (2014) Dominant negative MCP-1 blocks human osteoclast differentiation. Journal of Cellular Biochemistry, 115 2: 303-312. doi:10.1002/jcb.24663


Author Morrison, Nigel A.
Day, Christopher J.
Nicholson, Geoff C.
Title Dominant negative MCP-1 blocks human osteoclast differentiation
Journal name Journal of Cellular Biochemistry   Check publisher's open access policy
ISSN 0730-2312
1097-4644
Publication date 2014-02
Year available 2013
Sub-type Article (original research)
DOI 10.1002/jcb.24663
Open Access Status
Volume 115
Issue 2
Start page 303
End page 312
Total pages 10
Place of publication Hoboken, NJ, United States
Publisher John Wiley & Sons
Collection year 2014
Language eng
Abstract Human osteoclasts were differentiated using receptor activator of NFκB ligand (RANKL) and macrophage colony stimulating factor (M-CSF) from colony forming unit-granulocyte macrophage (CFU-GM) precursors of the myeloid lineage grown from umbilical cord blood. Gene expression profiling using quantitative polymerase chain reaction (Q-PCR) showed more than 1,000-fold induction of chemokine MCP-1 within 24 h of RANKL treatment. MCP-1 mRNA content exceeds that of other assayed chemokines (CCL1, 3, 4, and 5) at all time points up to day 14 of treatment. MCP-1 induction preceded peak induction of calcium signaling activator calmodulin 1 (CALM1) and transcription factors JUN and FOS, which were at 3 days. Key osteoclast related transcription factors NFATc1 and NFATc2 showed peak induction at 7 days, while marker genes for osteoclast function cathepsin K and tartrate resistance acid phosphatase (TRAP) were maximally induced at 14 days, corresponding with mature osteoclast function. To test whether the early and substantial peak in MCP-1 expression is part of human osteoclast differentiation events, a dominant negative inhibitor of MCP-1 (7ND) was added simultaneously with RANKL and M-CSF, resulting in blockade of CALM1, JUN and NFATc2 induction and strong inhibition of human osteoclast differentiation. These data show that a cascade of gene expression leading to osteoclast differentiation depends on intact early MCP-1 induction and signaling in human osteoclasts.
Keyword 7ND
Calmodulin
CFU-GM
Chemokine MCP-1 NFAT
Human Osteoclast
Inhibition
JUN
Myeloid
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Medicine Publications
 
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