title: AMD3100 Attenuates Matrix Metalloprotease-3 and -9 Expressions and Prevents Cartilage Degradation in a Monosodium Iodo-Acetate-Induced Rat Model of Temporomandibular Osteoarthritis.
abstract: OBJECTIVE
  Temporomandibular joint osteoarthritis (TMJOA) is an important subtype of temporomandibular disorder. This study investigated the inflammatory role of the stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor-4 (CXCR4) axis and the probable signaling pathway involved in matrix metalloprotease (MMP)-3 and MMP-9 productions stimulated by the SDF-1-CXCR4 axis in an experimental rat model of TMJOA.
  
  
  METHODS
  Rats were randomly divided into a control group, a pathologic model group, and an AMD3100 group. Effects of the bicyclam derivative AMD3100 (the specific antagonist of SDF-1-CXCR4 axis) were studied in TMJOA experimentally induced by monosodium iodo-acetate. Productions of SDF-1 and CXCR4 were compared in the normal and pathologic model groups, and cartilage changes and expressions of MMP-3, MMP-9, and phosphorylated extracellular signal-regulated kinase (p-ERK) were compared in the control, pathologic model, and AMD3100 groups.
  
  
  RESULTS
  Expressions of SDF-1 and CXCR4 in the pathologic model group were increased compared with the control group (P < .05). Releases of MMP-3, MMP-9, and p-ERK and cartilage changes were downregulated in the AMD3100 group compared with the pathologic model group (P < .05), and these changes occurred in a dose-dependent manner with AMD3100 concentrations. Moreover, there were strong predictive relations between the expression of p-ERK with MMP-3 (r(2) = 0.419; P < .001) and with MMP-9 (r(2) = 0.542; P < .001).
  
  
  CONCLUSIONS
  The SDF-1-CXCR4 signaling pathway plays a proinflammatory role in experimental TMJOA, the bicyclam derivative AMD3100 can alleviate the severity of experimental TMJOA, and there might be a potential relation between the SDF-1-CXCR4 axis and the ERK signaling pathway.
authors: Dental Student, Shandong Provincial Key Laboratory of Oral Tissue Regeneration and the Department of Prosthodontics, College of Stomatology, Shandong University, Jinan, China.
authors: Xiao-Yan
authors: XY
authors: Wang
authors: Dental Student, Shandong Provincial Key Laboratory of Oral Tissue Regeneration and the Department of Prosthodontics, College of Stomatology, Shandong University, Jinan, China.
authors: Yan
authors: Y
authors: Chen
authors: Dental Student, Shandong Provincial Key Laboratory of Oral Tissue Regeneration and the Department of Prosthodontics, College of Stomatology, Shandong University, Jinan, China.
authors: Xue-Jiao
authors: XJ
authors: Tang
authors: Dental Student, Shandong Provincial Key Laboratory of Oral Tissue Regeneration and the Department of Prosthodontics, College of Stomatology, Shandong University, Jinan, China.
authors: Lin-Hong
authors: LH
authors: Jiang
authors: Professor and Department Head, Shandong Provincial Key Laboratory of Oral Tissue Regeneration and the Department of Prosthodontics, College of Stomatology, Shandong University, Jinan, China. Electronic address: jiping@sdu.edu.cn.
authors: Ping
authors: P
authors: Ji
mesh_terms: D000818:Animals; D001596:Benzylamines; D002356:Cartilage / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000502:physiology; D000080027:Cyclams; D004195:Disease Models, Animal; D005260:Female; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D061965:Matrix Metalloproteinase Inhibitors / Q000627:therapeutic use*; D010003:Osteoarthritis / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000502:physiology; D019346:Sodium Acetate / Q000494:pharmacology; D013705:Temporomandibular Joint Disorders / Q000188:drug therapy*
chemical_list: D001596:Benzylamines; C575935:CXCL12 protein, rat; D054377:Chemokine CXCL12; C486264:Cxcr4 protein, rat; D000080027:Cyclams; D006571:Heterocyclic Compounds; D061965:Matrix Metalloproteinase Inhibitors; D019718:Receptors, CXCR4; D019346:Sodium Acetate; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; C088327:plerixafor