PMID- 23996571
OWN - NLM
STAT- MEDLINE
DCOM- 20140723
LR  - 20131216
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 115
IP  - 2
DP  - 2014 Feb
TI  - Dominant negative MCP-1 blocks human osteoclast differentiation.
PG  - 303-12
LID - 10.1002/jcb.24663 [doi]
AB  - Human osteoclasts were differentiated using receptor activator of NFkappaB 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.
CI  - (c) 2013 Wiley Periodicals, Inc.
FAU - Morrison, Nigel A
AU  - Morrison NA
AD  - School of Medical Science, Griffith University Gold Coast Campus, Parklands 
      Drive, Southport, Queensland, 4215, Australia.
FAU - Day, Christopher J
AU  - Day CJ
FAU - Nicholson, Geoff C
AU  - Nicholson GC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (CCL2 protein, human)
RN  - 0 (Calmodulin)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RANK Ligand)
RN  - 0 (TNFSF11 protein, human)
SB  - IM
MH  - Calmodulin/biosynthesis
MH  - Cell Differentiation/*genetics
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Developmental
MH  - Humans
MH  - Osteoclasts/*cytology
MH  - RANK Ligand/genetics
MH  - Signal Transduction/*genetics
MH  - Umbilical Cord/cytology
OTO - NOTNLM
OT  - 7ND
OT  - CALMODULIN
OT  - CFU-GM
OT  - CHEMOKINE MCP-1 NFAT
OT  - HUMAN OSTEOCLAST
OT  - INHIBITION
OT  - JUN
OT  - MYELOID
EDAT- 2013/09/03 06:00
MHDA- 2014/07/24 06:00
CRDT- 2013/09/03 06:00
PHST- 2013/08/22 00:00 [received]
PHST- 2013/08/27 00:00 [accepted]
PHST- 2013/09/03 06:00 [entrez]
PHST- 2013/09/03 06:00 [pubmed]
PHST- 2014/07/24 06:00 [medline]
AID - 10.1002/jcb.24663 [doi]
PST - ppublish
SO  - J Cell Biochem. 2014 Feb;115(2):303-12. doi: 10.1002/jcb.24663.