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PCR analysis of matrix metalloproteinase 3 (MMP-3) gene promoter polymorphism in ovarian cancer.

Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor-induced angiogenesis. The gene encoding MMP-3 is polymorphic and an insertion (6A)/deletion (5A) polymorphism (5A/6A polymorphism) in the MMP-3 gene may have functional significance in the regulation of its expression. In the present work the distribution of genotypes and frequency of alleles of the 5A/6A polymorphism in subjects with ovarian cancer were investigated. Paraffin embedded tumor tissues were obtained from 118 postmenopausal women with node-negative and node-positive ovarian cancer. The 5A/6A polymorphism was determined by PCR amplification using the allele specific primers. The distribution of the genotypes of the 5A/6A polymorphism in both control and study patients did not differ significantly (p>0.05) from those predicted by the Hardy-Weinberg distribution. There were no significant differences (p>0.05) in genotype distributions and allele frequencies between subgroups assigned to histological stage. The results suggest that the 5A/6A polymorphism of MMP-3 gene may not be linked with appearance and/or progression of ovarian cancer.

Adenocarcinoma↗

[Determination on contents of matrix metalloproteinase 3 and interleukin 1 in tissues of lumbar disc herniation and their roles in pathogenesis].

OBJECTIVE: To determine the contents of matrix metalloproteinase 3 (MMP-3) and interleukin 1 (IL-1) in the tissues of the lumbar disc herniation and to investigate their roles in the pathogenesis. METHODS: The tissues of the herniated lumbar disc were obtained from 30 patients undergoing surgery for persistent radiculopathy from June 2003 to December 2004 and at the same time these samples were divided into the following three experimental groups: the bulge group (n =11), the protrusion group (n = 9), and the prolapsus group (n = 10), 14 males, 16 females, aged 33-64 years. As the control group, 9 lumbar disc specimens were harvested from 9 patients (4 males, 5 females, aged 21-58 years) suffering from bursting fracture of the lumbar spine. The specimens were analyzed by the ELISA method for the contents of MMP-3 and IL-1. RESULTS: The contents of MMP-3(14.25+/-1. 32, 19.89+/-2.97, 20.69+/-2.18 ng/ml in the bulge group, protrusion group and prolapsus group, separately) and IL-1 (8.52+/-0.22, 11.88+/-0.52, 11.90+/-0.73 pg/ml in the bulge group, protrusion group and prolapsus group, separately) in the experimental groups were significantly higher than those in the control group. The contents of MMP-3 and IL-1 in the protrusion group were not significantly higher than those in the prolapsus group, but they were significantly higher than those in the bulge group(P<0.01). The contents of MMP-3 had a significant relationship with the contents of IL-1 in the three experimental groups and the control group(P<0. 01). CONCLUSION: The result demonstrates that the tissues of the lumbar disc herniation can produce both MMP-3 and IL-1, which may have an unknown but important relationship with each other.

Adult↗

Use of the plasma stromelysin (matrix metalloproteinase 3) concentration to predict joint space narrowing in knee osteoarthritis.

OBJECTIVE: To determine whether baseline or serial plasma concentrations of stromelysin (matrix metalloproteinase 3 [MMP-3]) protein might distinguish subjects with progressive radiographic knee osteoarthritis (OA) from those with stable disease. METHODS: Subjects were 120 women with unilateral knee OA who participated in a 30-month randomized, placebo-controlled trial of structure modification with doxycycline. Anteroposterior views of both knees in a semiflexed position were obtained at baseline, 16 months, and 30 months. Subjects were selected to obtain comparisons of plasma MMP-3 levels between 60 progressors (21 taking doxycycline, 39 taking placebo) and 60 nonprogressors (30 taking doxycycline, 30 taking placebo) with respect to medial joint space narrowing (JSN) in the index knee. Each group consisted of 30 subjects who exhibited significant increases in knee pain. Blood samples were obtained semiannually for MMP-3 assay. RESULTS: Subjects in the placebo group whose MMP-3 concentration was in the upper tertile of the baseline distribution showed a 4-fold increase in the odds of progression of JSN as compared with the lower tertile (odds ratio 4.12, P = 0.037). Baseline MMP-3 levels were unrelated to knee pain. The within-subject mean of serial MMP-3 concentrations was associated with concurrent JSN in the placebo group over the 0-16-month interval (b = 0.18 mm/SD increase in the mean MMP-3, P < 0.01) and over the 16-30-month interval (b = 0.15, P < 0.05). Similar evidence of concurrent validity was found in the placebo group for the maximum of intercurrent MMP-3 values. CONCLUSION: The baseline MMP-3 level was a significant predictor of JSN in this pilot study. Moreover, serial plasma MMP-3 levels reflected concurrent JSN in the placebo group over the 30-month period of observation.

Anti-Bacterial Agents↗

The functional (-1171 5A-->6A) polymorphisms of matrix metalloproteinase 3 gene as a risk factor for oral submucous fibrosis among male areca users.

BACKGROUND: Insertion/deletion (-1171 5A-->6A) polymorphisms in the promoter region of matrix metalloproteinase 3 (MMP3) gene result in different transcriptional activities. MMP3 is able to degrade collagens types II, V, IX, and X, and other extracellular matrix. The functional promoter polymorphism of MMP3 has been related to the susceptibility in some inflammatory diseases and metastasis of cancers. METHODS: Oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC) are prevalent among Asian areca users. In this study, genomic DNA obtained from the blood of OSCC (n = 150), OSF (n = 71), and control non-diseased areca user (n = 98) in male were subjected to polymerase chain reaction (PCR)-based genotyping of MMP3. RESULTS: The 5A genotype in MMP3 promoter was observed more frequently in OSF group than in control group (P = 0.01). No significant difference was noted between OSCC and control groups on the 5A genotype frequency (P = 0.18). No association was found between 5A genotype in MMP3 promoter and site or lymph node metastasis and stage of OSCC. CONCLUSION: The results indicated that the 5A genotype of MMP3 promoter was associated with the risk of OSF but not OSCC.

Adenine↗

Serum levels of matrix metalloproteinase 3 and macrophage colony-stimulating factor 1 correlate with disease activity in ankylosing spondylitis.

OBJECTIVE: To assess the usefulness of measuring serum matrix metalloproteinase 3 (MMP-3) and macrophage colony-stimulating factor (M-CSF) in patients with ankylosing spondylitis (AS). METHODS: Serum levels of MMP-3 and M-CSF were measured in AS patients who did and did not receive infliximab treatment. These were compared with those of 28 healthy subjects. RESULTS: In the group of AS patients not treated with biologics, both M-CSF and MMP-3 correlated with the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) values, but not with each other. Logistic regression analysis showed that MMP-3 values were high in those with severely active disease. Infusions of infliximab in AS patients led to a significant decrease in the values of the BASDAI as well as the serum MMP-3, but no change in the serum M-CSF values. CONCLUSION: MMP-3 and M-CSF are potentially useful markers of AS disease activity.

Adolescent↗

Lack of association of matrix metalloproteinase 3 (MMP3) genotypes with ankylosing spondylitis susceptibility and severity.

OBJECTIVE: To study the linkage and association of ankylosing spondylitis (AS) with genotypes for matrix metalloproteinase 3 (MMP3), a gene located at chromosome 11q22.3 and lying within the 101-124 cM region observed in a recent genome-wide scan as a region associated with AS susceptibility. METHODS: MMP3 genotypes were examined in 229 pedigrees with AS, 131 sporadic AS cases and 87 Caucasian controls. Eight single-nucleotide polymorphisms (SNPs) were selected and genotyped using Taqman. Non-parametric linkage (NPL) analysis was conducted between the eight MMP3 SNPs and AS using the NPL-all statistic and two-point parametric linkage analysis using GeneHunter Plus. Unrelated AS cases and controls were compared using chi2 statistics, and family-based controls using the transmission disequilibrium test and pedigree disequilibrium test. RESULTS: None of the eight MMP3 SNPs were significantly associated with AS, either using the 131 sporadic cases alone or in analyses which combined these cases with the 226 unrelated affected AS patients derived from the pedigrees. Analysis of linkage disequilibrium (LD) demonstrated that seven of the eight SNPs studied were in strong LD except for rs626750, which is about 6 kb upstream of the 5' end of the gene. No significant linkage was observed using NPL and LODs in the families. No association was seen of any of the MMP3 SNPs with disease severity (defined by patient functioning), as measured either by the Bath Ankylosing Spondylitis Functional Index or the modified Health Assessment Questionnaire. CONCLUSION: These data suggest that MMP3 genotypes are not involved in AS susceptibility or severity.

Adult↗

Serum matrix metalloproteinase 3 in early rheumatoid arthritis is correlated with disease activity and radiological progression.

OBJECTIVE: To analyze the clinical significance of serial measurements of serum matrix metalloproteinase 3 (MMP-3) levels in relation to markers of disease activity and radiological progression in early rheumatoid arthritis (RA). METHODS: In a 3 year prospective study of 33 patients with early RA (symptoms < 1 year at entry) monthly measurements of serum MMP-3 were transformed into time integrated values for 6 month periods for comparison with other markers of disease activity like swollen joint count (SJC), tender joint count (TJC), Ritchie articular index (RAI), the disease activity score (DAS), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and radiological progression, scored according to Sharp's method, in which erosions and joint space narrowing are scored separately and combined to a total Sharp score. RESULTS: Significant correlations were found between serum MMP-3 and SJC, ESR, and CRP during all periods and between 6 and 30 months with the DAS. There were no correlations between serum MMP-3 and TJC or the RAI. During the first 12 months serum MMP-3 was correlated only with the item joint space narrowing of the Sharp score. After 12 months of followup it was also correlated with the total Sharp score and after 18 months it was correlated with all 3 items of the Sharp score. There was a wide interindividual variation in the relation between serum MMP-3 and radiological progression but intraindividually this relation seemed to be rather constant. CONCLUSION: Time integrated values of serum MMP-3 are correlated with time integrated values of other markers of disease activity such as joint swelling, ESR, CRP, and the DAS. Of the radiological scores, as outcome measures, especially joint space narrowing correlated closely with cumulative serum MMP-3.

Adolescent↗

Investigation of the role of Endo180/urokinase-type plasminogen activator receptor-associated protein as a collagenase 3 (matrix metalloproteinase 13) receptor.

Procollagenase 3 can be activated by interaction with and cleavage by the cell-associated membrane type 1 metalloproteinase (MT1 MMP; MMP 14). It has also been shown to bind to a specific receptor, and is subsequently internalized via the low-density lipoprotein-related receptor by osteoblast cell lines. The receptor was identified as a recycling glycoprotein of the macrophage mannose receptor family, Endo180. In order to ascertain whether there is a relationship between Endo180 binding and procollagenase 3 activation, we have compared procollagenase 3 activation by an HT1080 fibrosarcoma cell line overexpressing MT1 MMP, without and with overexpression of Endo180. No difference in procollagenase 3 activation was observed, and neither was the enzyme bound to the cells or internalized. In contrast, the osteoblast cell lines, MG63 and UMR-106, both bound and internalized procollagenase 3. However, immunolocalization studies showed that the Endo180 abundantly expressed by these cells did not co-localize with the procollagenase 3. In further biochemical studies we confirmed that procollagenase 3 did not bind to Endo180, using both ligand- blotting and immunoprecipitation techniques. We conclude that Endo180 is unlikely to be a receptor for collagenase 3 in relation to either its activation or cell binding and internalization, and that other interaction partners must be sought.

Blotting, Western↗

Serum matrix metalloproteinase 3 as a predictor of the degree of joint destruction during the six months after measurement, in patients with early rheumatoid arthritis.

OBJECTIVE: To evaluate whether matrix metalloproteinase 3 (MMP-3), a proteinase that is expressed in rheumatoid synovial tissue and shows potent activity in degrading the proteoglycan of cartilage, plays a pivotal role in the joint destruction seen in early rheumatoid arthritis (RA). METHODS: In a prospective study of patients with early RA, the relationship between the serum concentration of MMP-3, as determined by a sandwich enzyme immunoassay system, and the progression of joint destruction in patients with early RA, as measured by the Larsen radiologic score, was investigated. RESULTS: Serum MMP-3 levels were elevated in the RA patients compared with healthy controls, not only in the late stage, but also in the early stage of the disease in patients whose duration of RA was <4 months. The serum MMP-3 level at entry into the study had a strong correlation with the Larsen score at 6 months and 12 months after entry (r = 0.58 and r = 0.49, respectively). Similarly, the serum MMP-3 level at 12 months and 24 months after entry showed a positive association with the Larsen score in the subsequent 6-12 months. Suppression of the serum MMP-3 level in the first year led to a decline in joint damage in the second year. CONCLUSION: The serum concentration of MMP-3 is a useful marker for predicting bone damage in the early stage of RA, and the suppression of MMP-3 production may be an effective therapeutic approach for patients with early RA.

Adult↗

Serum matrix metalloproteinase 3 levels in comparison to C-reactive protein in periods with and without progression of radiological damage in patients with early rheumatoid arthritis.

OBJECTIVE: To evaluate serum matrix metalloproteinase 3 (MMP-3) levels in comparison to C-reactive protein (CRP) in periods with and without progression of radiological damage in patients with early rheumatoid arthritis (RA). METHODS: Thirty-two patients with RA and radiological progression (> or = 5 points according to the Sharp/van der Heijde method) during 6 months followed by a 6-month period without radiological progression (< or = 1 point) were selected from a prospective follow-up study of early RA patients. Serum MMP-3 levels, CRP, the erythrocyte sedimentation rate (ESR), disease activity index (DAS), swollen joint count (SJC), tender joint count (TJC), and Ritchie articular index (RAI) were measured monthly and results were transformed into mean values for the 6-month periods. RESULTS: During the period with radiological progression the mean serum MMP-3 correlated significantly with the mean CRP (r = 0.68, p < 0.001), ESR (r = 0.54, p = 0.001) and swollen joint count (r = 0.48, p = 0.006). In the period without radiological progression the mean serum MMP-3 only correlated with the mean CRP (r = 0.44, p = 0.012). Individual changes--expressed in percentages (%)--between the two periods showed a decrease in both the mean serum MMP-3 and CRP in 19 and an increase in 3 patients, in parallel with other markers of disease activity in these patients (69% of cases). The individual change (%) in mean serum MMP-3 or CRP did not correlate with the difference in radiological progression between the two periods. CONCLUSIONS: Serum MMP-3 and CRP are closely related and there seems to be no difference between serum MMP-3 and CRP with regard to the monitoring of the progression of radiological damage.

Adult↗

Expression of mRNA for membrane-type 1, 2, and 3 matrix metalloproteinases in human laryngeal cancer.

OBJECTIVE: To investigate correlation of expressions of membrane-type 1, 2, and 3 matrix metalloproteinases (MT1, MT2, and MT3-MMP) to the invasion and metastases in laryngeal cancer. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the mRNA level of MT1, MT2, and MT3-MMP in 24 patients with laryngeal cancer. The relationships of these three MT-MMP expressions to clinicopathology were analyzed by statistics. RESULTS: The expressions of MT1, MT2, and MT3-MMP were significantly higher in laryngeal cancer tissues than those in para-tumorous tissues (P < 0.01) and had a close relationship with invasive depth (P < 0.05). But no significantly different expressions of these three MT-MMPs were found in different primary location and different histological grade of laryngeal cancer (P > 0.05). The expression of MT1-MMP was obviously higher in patients with metastatic lymph nodes than that in patients without metastatic lymph nodes (P < 0.05). CONCLUSION: MT1, MT2, and MT3-MMP play an important role in the progression of laryngeal cancer, and MT1-MMP may serve as a reliable marker in estimating invasive and metastatic potency of laryngeal cancer. Suppressing expressions of MT1, MT2, and MT3-MMP early may inhibit the invasion and metastases of laryngeal cancer.

Adult↗

Stromelysin 1 (matrix metalloproteinase 3) and HLA-DRB1 gene polymorphisms: Association with severity and progression of rheumatoid arthritis in a prospective study.

OBJECTIVE: To test the hypothesis of an association between a polymorphism in the matrix metalloproteinase 3 (MMP-3) gene promoter and the susceptibility, severity, and progression of rheumatoid arthritis (RA), and to further document the association between HLA-DRB1 alleles encoding the shared epitope (SE) and the severity and progression of RA. METHODS: Patients with early RA (n = 103) were included in this prospective study. A total radiographic damage score (TDS; by the Sharp/van der Heijde method) was used to quantify RA severity at baseline and after 4 years of followup. The 5A/6A biallelic polymorphism in the MMP-3 gene promoter was analyzed using fluorescence-based polymerase chain reaction (PCR). HLA-DRB1 genotyping was performed using PCR methods. Control subjects (n = 127) were unrelated healthy individuals. RESULTS: MMP-3 allele carriage rates and allele and genotype frequencies did not differ between patients and controls. The MMP-3 6A/6A genotype was associated with the highest TDS both at baseline and after a 4-year followup and with the highest progression of the TDS over the 4 years of followup. The DRB1 SE+/+ genotype was associated with the highest TDS after a 4-year followup and with the highest progression of the TDS over the 4 years of followup. Patients homozygous for MMP-3 6A and DRB1 SE had the highest progression of the TDS. CONCLUSION: This study provides the first evidence of an association between a polymorphism in the MMP-3 gene promoter and the severity and progression of RA, but not RA susceptibility. Investigation of this polymorphism could be combined with that of DRB1 gene polymorphism to improve the predictive accuracy and management strategy in early RA.

Alleles↗

Identification of rabbit uterine cervical procollagenase activator as rabbit matrix metalloproteinase 3 (stromelysin).

1. We previously reported an endogenous activator of procollagenase from the culture medium of rabbit uterine cervical fibroblasts (Ishibashi et al. (1987) Biochem. J. 241, 527-534). 2. Similar activator was also purified and characterized from rabbit synovial fibroblasts (Vater et al. (1983) J. biol. Chem. 258, 9374-9382), but its mode of activation of procollagenase was reported to be different from that of purified activator from uterine cervical fibroblasts. 3. Here we report the comparative studies of the two activators of procollagenase and demonstrate that they are identified as matrix metalloproteinase 3 (stromelysin) by their immunological and functional criteria. The specific role of the activator in procollagenase activation is also described.

Animals↗

Haplotype analysis of the matrix metalloproteinase 3 gene and myocardial infarction in a Chinese Han population. The Beijing atherosclerosis study.

Matrix metalloproteinase (MMP) 3 plays an important role in the pathogenesis of myocardial infarction (MI). Up to now, there has been conflicting data regarding the possible contribution of the MMP3 -1612 5A/6A promoter polymorphism to MI. In this study, we have investigated the possible association of three polymorphisms (-1612 5A/6A, -376C/G, Glu45Lys) in the MMP3 gene with MI in a Chinese Han population. The polymorphisms were analyzed in 509 patients with MI, and in 518 healthy controls. The frequency of the 5A allele was 14% in the healthy controls, which is less than in Western populations (40%-52%). Logistic regression analyses of individual polymorphisms indicated that individuals carrying the -1612 5A allele had an increased risk of MI (odds ratio [OR] 1.75, 95% confidence interval [CI] 1.28 to 2.40), as did those carrying the -376 G allele (OR 1.78, 95% CI 1.33 to 2.38). The three polymorphisms studied were found to be in strong linkage disequilibria. Haplotype analyses showed that the 5A-G-Lys haplotype (-1612 5A, -376G and 45Lys) was independently associated with susceptibility to MI. Taken together, the effect of the MMP3 polymorphisms studied may be attributable to the -1612 5A/6A polymorphism. We conclude that the MMP3 -1612 5A/6A polymorphism is associated with MI in our population, implying that individuals of the 5A allele carriers have an increased risk of suffering MI.

Case-Control Studies↗

Degradation of basement membranes by human matrix metalloproteinase 3 (stromelysin).

Connective tissue cells synthesize and secrete a group of matrix metalloproteinases (MMPs), all of which are capable of degrading the extracellular-matrix components. One of them, MMP-3 (stromelysin) has been shown to degrade purified basement-membrane components, collagen IV and laminin [Okada, Y., Nagase, H. & Harris, E. D., Jr. (1986) J. Biol. Chem. 261, 14245-14255]. Here we report that MMP-3 degrades collagen IV and laminin in intact basement membranes from bovine glomeruli (GBM) and bovine anterior-lens capsules (LBM). Degradation products were analysed by SDS/polyacrylamide-gel electrophoresis to determine the number and sizes of polypeptide fragments. Immunoblotting techniques were used to identify the origins of the fragments, i.e. collagen IV or laminin. The fragments of collagen IV were further mapped using specific antibodies that recognize the N-terminal (7 S) domain, the C-terminal (NC-1) domain, or the major triple-helical region between the terminal domains. Degradation of collagen IV was extensive; many fragments were found, from both GBM and LBM, in the Mr range 25,000-380,000. A large fragment of laminin (Mr greater than 380,000) was found in the GBM digests without reduction, but it dissociated into 220,000-Mr chains upon reduction. The results suggest that MMP-3 plays an important role in the catabolism of basement membranes.

Animals↗

Serum and synovial fluid concentrations of matrix metalloproteinases 3 and its tissue inhibitor 1 in juvenile idiopathic arthritides.

OBJECTIVE: Matrix metalloproteinases (MMP) are a large family of proteolytic enzymes involved in the remodeling of extracellular matrix during tissue resorption in idiopathic arthritides. We investigated serum and synovial fluid (SF) concentrations of MMP-3 and its tissue inhibitor (TIMP-1) in juvenile idiopathic arthritides (JIA). METHODS: Sera from 45 patients with active, 15 patients with inactive JIA, and 15 healthy controls were evaluated by ELISA for MMP-3 (stromelysin-1), TIMP-1, and soluble p75 tumor necrosis factor receptor (sTNFR). Paired SF concentrations were evaluated in 19 patients with JIA. RESULTS: MMP-3 serum concentrations were significantly higher in patients with active poly- and oligoarticular JIA versus inactive patients (p = 0.04 and p = 0.02, respectively) and healthy controls (p < 0.001 for both). Serum MMP-3, but not TIMP-1, concentration displayed a variable degree of correlation with clinical and laboratory variables of disease activity and with p75 sTNFR concentrations (r = 0.37, p = 0.005). SF MMP-3 concentrations were 30-300 times higher than those found in paired sera (p < 0.001, Wilcoxon rank test). A clear inversion of MMP-3/TIMP-1 ratio was observed when sera (median 0.31. range 0.02-1.5) were compared with the corresponding SF samples (5.3, range 4.9-5.5; p < 0.001). CONCLUSION: MMP-3 (stromelysin-1) is clearly overexpressed in SF of patients with JIA. An inadequate counter-expression of TIMP-1 may represent a crucial event for the development and perpetuation of tissue damage.

Adolescent↗

[Effects of infliximab and etanercept, two types of anti-tumor necrosis factor-alpha inhibitor on serum level of matrix metalloproteinase 3 expression in patients with ankylosing spondylitis].

OBJECTIVE: To evaluate the effect of Infliximab and Etanercept two types of anti-tumor necrosis factor-alpha (TNF-alpha) inhibitors, on the serum level of matrix metalloproteinase 3 (MMP-3) in the pathogenesis of ankylosing spondylitis (AS). METHOD: 47 patients with AS, 40 males and 7 females, aged 17 - 51, were treated with Infliximab (5 mg/kg i.v at weeks 0, 2, and 6); and 26 patients with AS were treated with Etanercept (25 mg, twice a week for 12 weeks). Clinical data including Bath AS indices (BASDAI and BASFI) and sera were collected at baseline and other different times. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were measured. Serum levels of MMP-3 were measured with MMP-3 ELISA kits. RESULTS: Two, six, and ten weeks after Infliximab treatment the levels of ESR, CRP, and serum MMP-3 of the AS patients were all significantly lower than the baseline level (all P < 0.01), and the serum MMP-3 levels were all significantly correlated with ESR (all P < 0.05). In the Etanercept group 1, 2, 4, 8, and 12 weeks after treatment the levels of serum MMP-3, ESR, CRP, BASDAI, and BASFI were all significantly lower than the baseline levels (all P < 0.01); before the treatment ESR was significantly correlated with CRP (r = 0.80, P < 0.01), BASDAI was significantly correlated with BASFI (r = 0.48, P < 0.05), and MMP-3 was significantly correlated with ESR (r = 0.74, P < 0.01) and with CRP (r = 0.72, P < 0.01); and 12 weeks after the treatment significant correlation still existed between ESR and CRP (r = 0.40, P < 0.05), BASDAI and BASFI (r = 0.89, P < 0.01), and MMP-3 and ESR (r = 0.43, P = 0.029), however, there was no significant correlation between CRP and serum level of MMP-3 (r = 0.37, P = 0.061). CONCLUSION: Infliximab and Etanercept, 2 anti-TNF-alpha inhibitors, not only significantly decrease the ESR and CRP, but also decrease the serum level of MMP-3 of patients with AS. MMP-3 is involved in the pathogenesis and disease activity of AS. MMP-3 is also a potentially useful marker of AS disease activity and useful parameter to assess the effectiveness of anti-TNF-alpha inhibitor in treatment of AS.

Adolescent↗

Evidence that human rheumatoid synovial matrix metalloproteinase 3 is an endogenous activator of procollagenase.

The treatment of crude culture medium from human rheumatoid synovial cells with 4-aminophenylmercuric acetate (APMA) or trypsin results in the activation of procollagenase. This process was shown to be dependent on the presence of matrix metalloproteinase 3 (MMP-3). MMP-3 can directly activate procollagenase without changing the apparent molecular weight of procollagenase. This activity was accelerated in the presence of APMA. We propose that MMP-3 plays an important role in connective tissue destruction through the activation of procollagenase in addition to its direct action on components of the extracellular matrix.

Arthritis, Rheumatoid↗