[Influence on matrix metalloproteinases 3, 9, and 13 levels after blocking stromal cell derived factor 1/chemokine receptor 4 signaling pathway with AMD3100].
OBJECTIVE
To investigate the influence on matrix metalloproteinases (MMP) 3, 9, and 13 levels of human articular cartilage cells after blocking stromal cell derived factor 1 (SDF-1)/chemokine receptor 4 (CXCR4) signaling pathway with AMD3100 and to define the function mechanism of AMD3100.


METHODS
A total of 144 cartilage blocks from 12 osteoarthritis (OA) patients undergoing total knee arthroplasty (OA cartilage group) and 144 normal cartilage blocks (Mankin score of 0 or 1) from 12 patients undergoing traumatic amputation (normal cartilage group). OA cartilage group was further divided into subgroups A1, B1, and C1, and normal cartilage group into subgroups A2, B2, and C2. The cartilage tissues were cultured in DMEM solution containing 100 ng/mL SDF-1 and 1 000 nmol/L AMD3100 in subgroup A, 100 ng/mL SDF-1 and 1 000 nmol/L MAB310 in subgroup B, and 100 ng/mL SDF-1 in subgroup C, respectively. The levels of MMP-3, 9, and 13 were measured by ELISA; the expressions of MMP-3, 9, and 13mRNA were tested by RT-PCR.


RESULTS
ELISA and RT-PCR results showed that the levels of MMP-3, 9, and 13 and the expressions of MMP-3, 9, and 13 mRNA were significantly lower in subgroup A than in subgroups B and C at the same time points (P < 0.05); the levels of MMP-3, 9, and 13 and the expressions of MMP-3, 9, and 13 mRNA were significantly higher in OA cartilage group than in normal cartilage group at the same time points (P < 0.05).


CONCLUSIONS
SDF-1 could induce overexpression and release of MMP-3, 9, and 13 in the articular cartilage through the SDF-1/CXCR4 signaling pathway; AMD3100 could reduce the mRNA expressions and secretion of MMP-3, 9, and 13 in OA cartilage by blocking the SDF-1/CXCR4 signaling pathway; but AMD3100 could not make the secretion of MMP-3, 9, and 13 return to normal levels in OA cartilage.
Department of Sports Medicine, the First Hospital Affiliated to Kunming Medical University, Kunming Yunnan, 650000, P.R.China.
Yanlin
Y
Li
Guoliang
G
Wang
Bin
B
Cao
Gang
G
Gao
Ke
K
Ma
Wendong
W
Chen
Peng
P
Xu
Guang
G
Yang
D000328:Adult; D000368:Aged; D001596:Benzylamines; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D000080027:Cyclams; D005260:Female; D006571:Heterocyclic Compounds / Q000494:pharmacology*; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects
D001596:Benzylamines; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D020782:Matrix Metalloproteinases; C088327:plerixafor