PMID- 24123855
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20211021
IS  - 1552-4965 (Electronic)
IS  - 1549-3296 (Print)
IS  - 1549-3296 (Linking)
VI  - 102
IP  - 9
DP  - 2014 Sep
TI  - Mutant monocyte chemoattractant protein 1 protein attenuates migration of and 
      inflammatory cytokine release by macrophages exposed to orthopedic implant wear 
      particles.
PG  - 3291-7
LID - 10.1002/jbm.a.34981 [doi]
AB  - Wear particles generated from total joint replacements can stimulate macrophages 
      to release chemokines, such as monocyte chemoattractant protein 1 (MCP-1), which 
      is the most important chemokine regulating systemic and local cell trafficking 
      and infiltration of monocyte/macrophages in chronic inflammation. One possible 
      strategy to curtail the adverse events associated with wear particles is to 
      mitigate migration and activation of monocyte/macrophages. The purpose of this 
      study is to modulate the adverse effects of particulate biomaterials and 
      inflammatory stimuli such as endotoxin by interfering with the biological effects 
      of the chemokine MCP-1. In the current study, the function of MCP-1 was inhibited 
      by the mutant MCP-1 protein called 7ND, which blocks its receptor, the C-C 
      chemokine receptor type 2 (CCR2) on macrophages. Addition of 7ND decreased 
      MCP-1-induced migration of THP-1 cells in cell migration experiments in a 
      dose-dependent manner. Conditioned media from murine macrophages exposed to 
      clinically relevant polymethylmethacrylate (PMMA) particles with/without 
      endotoxin [lipopolysaccharide (LPS)] had a chemotactic effect on human 
      macrophages, which was decreased dramatically by 7ND. 7ND demonstrated no adverse 
      effects on the viability of macrophages, and the capability of mesenchymal stem 
      cells (MSCs) to form bone at the doses tested. Finally, proinflammatory cytokine 
      production was mitigated when macrophages were exposed to PMMA particles 
      with/without LPS in the presence of 7ND. Our studies confirm that the MCP-1 
      mutant protein 7ND can decrease macrophage migration and inflammatory cytokine 
      release without adverse effects at the doses tested. Local delivery of 7ND at the 
      implant site may provide a therapeutic strategy to diminish particle-associated 
      periprosthetic inflammation and osteolysis.
CI  - (c) 2013 Wiley Periodicals, Inc.
FAU - Yao, Zhenyu
AU  - Yao Z
AD  - Department of Orthopaedic Surgery, Stanford University, Stanford, California.
FAU - Keeney, Michael
AU  - Keeney M
FAU - Lin, Tzu-Hua
AU  - Lin TH
FAU - Pajarinen, Jukka
AU  - Pajarinen J
FAU - Barcay, Katherine
AU  - Barcay K
FAU - Waters, Heather
AU  - Waters H
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Yang, Fan
AU  - Yang F
FAU - Goodman, Stuart
AU  - Goodman S
LA  - eng
GR  - R01 AR055650/AR/NIAMS NIH HHS/United States
GR  - R01 AR063717/AR/NIAMS NIH HHS/United States
GR  - 2R01AR055650-05/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131120
PL  - United States
TA  - J Biomed Mater Res A
JT  - Journal of biomedical materials research. Part A
JID - 101234237
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 9011-14-7 (Polymethyl Methacrylate)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Survival
MH  - Chemokine CCL2/*genetics/immunology
MH  - Chemotaxis
MH  - Cytokines/*immunology
MH  - Humans
MH  - Inflammation/*etiology/genetics/immunology
MH  - Macrophages/cytology/*immunology/metabolism
MH  - Mice
MH  - Mutation
MH  - Polymethyl Methacrylate/*adverse effects
MH  - Prostheses and Implants/*adverse effects
PMC - PMC4035458
MID - NIHMS581336
OTO - NOTNLM
OT  - chemotaxis
OT  - cytokines
OT  - inflammation
OT  - macrophages
OT  - particles
EDAT- 2013/10/15 06:00
MHDA- 2015/03/31 06:00
PMCR- 2014/09/01
CRDT- 2013/10/15 06:00
PHST- 2013/05/03 00:00 [received]
PHST- 2013/09/11 00:00 [revised]
PHST- 2013/09/25 00:00 [accepted]
PHST- 2013/10/15 06:00 [entrez]
PHST- 2013/10/15 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - 10.1002/jbm.a.34981 [doi]
PST - ppublish
SO  - J Biomed Mater Res A. 2014 Sep;102(9):3291-7. doi: 10.1002/jbm.a.34981. Epub 2013 
      Nov 20.