PMID- 20540256
OWN - NLM
STAT- MEDLINE
DCOM- 20110111
LR  - 20131121
IS  - 1002-1892 (Print)
IS  - 1002-1892 (Linking)
VI  - 24
IP  - 5
DP  - 2010 May
TI  - [Experimental study on simvastatin in prevention and treatment of aseptic 
      loosening of prosthesis].
PG  - 544-7
AB  - OBJECTIVE: To evaluate the mechanisms of p42/p44 kinase phosphorylation in cell 
      models and to investigate the effect of simvastatin on the prevention and 
      treatment of aseptic loosening of prosthesis by observing the influence of 
      simvastatin on the levels of tumor necrosis factor alpha (TNF-alpha) and monocyte 
      chemoattractant protein 1 (MCP-1) of human peripheral blood mononuclear cell 
      (PBMC) challenged with titanium particles. METHODS: PBMC from 45 mL peripheral 
      blood of healthy adult voluntary donators, were separated and cultured, and 
      divided into 5 groups according to different culture medium: group A, PBMC and 
      titanium particles; group B, PBMC and titanium particles with 1 x 10(-5) mol/L 
      simvastatin; group C, PBMC and titanium particles with 1 x 10(-6) mol/L 
      simvastatin; group D, PBMC and titanium particles with 1 x 10(-7) mol/L 
      simvastatin; and group E, PBMC and titanium particles with the extracellular 
      signal-regulated kinase (ERK1/2) inhibitor U0126. The contents of TNF-alpha and 
      MCP-1 were tested by ELISA after 24 hours of culture. PBMC were pretreated with 
      different medium grouping as groups A, B, C, D, and E for 60 minutes, and were 
      challenged with titanium particles for 30 minutes and 60 minutes, then the level 
      of ERK1/2 expression was tested by Western blot. RESULTS: In groups A, B, C, D, 
      and E, the absorbance (A) values of TNF-alpha were 1.115 5 +/- 0.243 6, 0.693 6 
      +/- 0.354 3, 0.695 7 +/- 0.387 3, 0.716 4 +/- 0.478 9, and 0.263 5 +/- 0.1016, 
      respectively; and the A values of MCP-1 were 1.4210 +/- 0.105 3, 0.915 1 +/- 
      0.411 3, 1.003 5 +/- 0.464 2, 1.102 0 +/- 0.353 9, and 0.2713 +/- 0.145 1, 
      respectively. The levels of TNF-alpha and MCP-1 in group A were significantly 
      higher than others, showing significant differences (P < 0.05). There were 
      significant differences between group E and groups B, C, and D (P < 0.05), 
      between group B and groups C, D (P < 0.05); no significant difference between 
      group C and group D (P > 0.05). Western blot results showed the expression of 
      ERK1/2 in all groups at 30 minutes and 60 minutes of culture. The levels of 
      ERK1/2 expression were 1.612 1 +/- 0.068 2, 1.078 1 +/- 0.072 8, 1.268 7 +/- 
      0.223 1, 1.439 7 +/- 0.180 1, and 0.732 0 +/- 0.110 4 in groups A, B, C, D, and 
      E, respectively; showing significant differences between groups (P < 0.05). 
      CONCLUSION: ERK1/2 is a phosphorylated protein after stimulated by wear 
      particles; it is also one of the most important cell signaling activation of 
      macrophage. Simvastatin can inhibit the expression of bone absorptive factors 
      induced by wear particles and may be used in the prevention and treatment of 
      aseptic loosening of prosthesis.
FAU - Wang, Zhen
AU  - Wang Z
AD  - Graduate School of Ningxia Medical University, Yinchuan Ningxia 750004, PR China.
FAU - Gao, Xiwu
AU  - Gao X
FAU - Sun, Kening
AU  - Sun K
FAU - Jin, Qunhua
AU  - Jin Q
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi
JT  - Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = 
      Chinese journal of reparative and reconstructive surgery
JID - 9425194
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - AGG2FN16EV (Simvastatin)
RN  - D1JT611TNE (Titanium)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Adult
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - *Joint Prosthesis
MH  - Leukocytes, Mononuclear/*drug effects/*metabolism
MH  - Monocytes/drug effects/metabolism
MH  - Prosthesis Failure
MH  - Simvastatin/*pharmacology
MH  - Titanium/pharmacology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2010/06/15 06:00
MHDA- 2011/01/12 06:00
CRDT- 2010/06/15 06:00
PHST- 2010/06/15 06:00 [entrez]
PHST- 2010/06/15 06:00 [pubmed]
PHST- 2011/01/12 06:00 [medline]
PST - ppublish
SO  - Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2010 May;24(5):544-7.