OBJECTIVE: To investigate the expression level of serum matrix metalloproteinase 3 (MMP3) in early rheumatoid arthritis (ERA) patients with normal C-reaction protein (CRP) or erythrocyte sedimentation rate (ESR), and the significance in disease assessment. METHODS: In the study, 133 cases of early RA patients, 25 osteoarthritis (OA) patients and 60 healthy controls in Peking University People's Hospital from 2011 to 2015 were included. The RA patients were further divided into 4 groups according to levels of CRP and ESR: 88 patients with increased CRP and increased ESR, 15 patients with normal CRP and normal ESR, 17 patients with normal CRP but increased ESR, and 13 patients with increased CRP but normal ESR. All the clinical information of the patients was collected, and the serum MMP3 levels of both patients and healthy controls were detected by enzyme-linked immune sorbent assay (ELISA). RESULTS: The serum MMP3 level of RA patients with normal CRP and/or normal ESR [(72.89±6.34) μg/L] was obviously higher than that of OA patients [(42.87±4.14) μg/L] (P=0.002) and healthy controls [(31.62±2.88) μg/L] (P<0.001). The serum MMP3 levels of the patients with normal CRP and normal ESR [(47.04±9.64) μg/L] were higher than those of the healthy controls, and there was statistical significance between the two groups (P<0.05). The serum MMP3 levels of the patients with increased CRP but normal ESR [(94.18±9.11) μg/L] and the patients with normal CRP but increased ESR [(79.42±10.60) μg/L] were both higher than those of the OA patients and healthy controls, and there was obvious statistical difference (P<0.05). In the early RA patients with normal CRP and/or normal ESR, the serum MMP3 level was positively correlated with the CRP level (r=0.336, P=0.024). The positive rate of MMP3 in the patients with normal CRP and/or normal ESR was 44.44%, higher than the positive rate of CRP (28.89%) and the positive rate of ESR (37.78%). In these early RA patients, the positive rate was 52.94% in the patients with normal CRP but increased ESR and 53.85% in the patients with increased CRP but normal ESR. CONCLUSION The detection of the serum MMP3 level was significant in the assessment of early RA patients within 2-year duration who had normal CRP or ESR value.
Arthritis, Rheumatoid/diagnosis* ; Blood Sedimentation ; Humans ; Matrix Metalloproteinase 3/blood* ; Osteoarthritis

OBJECTIVETo study possible correlation between matrix metalloproteinases (MMPs) activities and myocardial injury after asphyxia in neonatal Wistar rats.

METHODSixty neonatal Wistar rats (7 to 10 days old) were randomly divided into four groups: control group (group D); asphyxia groups A, B and C (1 day, 7 days, 14 days after asphyxia), every group had 15 rats. In the asphyxia groups, animal model was produced by normobaric asphyxia. Groups A, B and C were sacrificed on days 1, 7 and 14 days after asphyxia, and group D rats were sacrificed on the 7 th day. Then the heart blood was taken to tested the serum cTnI. The myocardial MMPs-3 and 9 activity was measured by using immunohistochemical assay. Histological sections of the hearts were stained with hematoxylin-eosin and myocardial histopathological scores were determined under an optical microscope. The amount of myocardial collagen was measured by means of chloramines T.

RESULTScTnI was significantly higher in group A (0.3680 +/- 0.40 ng/ml) than group D (0.0783 +/- 0.06 ng/ml) (P < 0.05), and was lower in group B (0.1889 +/- 0.15 ng/ml) but still significantly different from that of group D (P < 0.05), and declined to the normal level in group C (0.1338 +/- 0.07 ng/ml), but the difference between groups C and D was not significant (P > 0.05). Myocardial tissue MMPs-3 activity was transiently high in group A (0.1847 +/- 0.04), higher in group B (0.2780 +/- 0.05) as compared to group D (0.1213 +/- 0.03) (P < 0.05 for all). The activity of MMPs-3 increased earlier than that of MMPs-9. The amount of myocardial collagen of group B (38.94 +/- 0.67) and C (40.69 +/- 0.75) was significantly greater than that of group D (P < 0.05). Myoardial tissue MMPs-3 and MMPs-9 positively correlated with myocardial histopathological scores (r = 0.669, 0.667, P < 0.05) and myocardial collagen (r = 0.482, 0.679, P < 0.05).

CONCLUSIONSIn rats with asphyxia, there was an excess activation of myocardial MMPs-3 and MMPs-9 activities and secondary to which, the quantity of myocardial collagen increased. The injuries of myocardium may be closely associated with myocardial tissue MMPs. MMPs may be used to evaluate the severity of myocardial interstitial damage.

Animals ; Asphyxia ; metabolism ; pathology ; Collagen ; metabolism ; Disease Models, Animal ; Matrix Metalloproteinase 3 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Myocardium ; metabolism ; pathology ; Rats ; Rats, Wistar ; Troponin I ; blood

OBJECTIVETo investigate the effect of the active components from Red Paeonia and Rhizoma chuanxiong (in Xiongshao Capsule, XSC) on matrix metalloproteinases (MMPs) in rabbit model of atherosclerosis.

METHODSFifty New Zealand rabbits were randomly divided into the normal control group (A), the model control group (B), the Simvastatin treated group (C), the low-dose XSC treated group (D) and the high-dose XSC treated group (E), 10 in each group. Rabbits in the normal control group were fed with normal diet, while those in the other four groups were fed with high fat diet and duplicated after two weeks feeding into model of abdominal aortic atherosclerosis by balloon angioplasty. In the 6 successive weeks feeding of high fat diet, Simvastatin 2.5 mg/kg, XSC 0.24 g/kg and 0.48 g/kg per day was given respectively to the rabbits in the three treated groups. Blood sample was collected for determining the level of blood lipids; serum MMP-3 and MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) with enzyme-linked immunoassay; and the protein expression of MMP-3 and cluster of differentiation antigen 40 ligand (CD40L) in plaque were detected with immunohistochemical method.

RESULTSCompared with Group B, the serum levels of MMP-3 and MMP-9; the expression of MMP-3 and CD40L in plaque; and the blood content of total cholesterol in the three treated groups were significantly lower (P < 0.05 or P < 0.01). Besides, the content of triglyceride and low-density lipoprotein cholesterol were significantly reduced in Group C, while the TIMP-1 showed no statistical difference among different groups (P > 0.05).

CONCLUSIONThe active components of Red Paeonia and Rhizoma chuanxiong play a definite role in stabilizing the atherosclerotic plaque in rabbits, one of their possible mechanisms may be by way of inhibiting the expressions of MMP-3, MMP-9 in vascular walls and blood serum.

Animals ; Atherosclerosis ; drug therapy ; enzymology ; Drugs, Chinese Herbal ; pharmacology ; Male ; Matrix Metalloproteinase 3 ; blood ; Matrix Metalloproteinase 9 ; blood ; Paeonia ; chemistry ; Phytotherapy ; Rabbits ; Random Allocation ; Tissue Inhibitor of Metalloproteinase-1 ; blood

OBJECTIVETo explore the clinical significance of serum matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinase-1 (TIMP-1), and monocyte CD147 in rheumatoid arthritis (RA) patients of damp-heat Bi-syndrome (DHBS) and of cold-damp Bi-syndrome (CDBS).

METHODSThe clinical data of 22 patients from inpatients and outpatients with RA were collected, and their peripheral blood was withdrawal. The disease activity scores [DAS28(4)] were assessed. The serum levels of MMP-3 and TIMP-1 were detected by double antibody sandwich enzyme linked immunosorbent assay (ELISA). The mean fluorescence intensity (MFI) and the expression percentage of CD147 on CD14+ monocytes were detected by flow cytometry. The difference of each index between RA patients of DHBS and RA patients of CDBS was analyzed.

RESULTSThe level of serum MMP-3 and the MFI of CD147 on the monocyte surface were obviously higher in RA patients of DHBS than in those of CDBS and the normal control group (P < 0.05). The concentration of serum TIMP-1 was obviously higher in RA patients of DHBS than in those of the normal control group (P < 0.05), while there was no statistical difference between the two syndrome types. The percentage of CD147 expression was obviously lower in DHBS than in those of CDBS and the normal control group (P < 0.05).

CONCLUSIONSIncreased serum MMP-3 level of RA patients of DHBS might result in destroy of joint cartilages and sclerotin. The significant increase of MFI and decreased expression percentage of monocyte CD147 might be the results of increased disease activity of RA and monocyte migration to the synovial membrane tissue.

Adult ; Aged ; Arthritis, Rheumatoid ; blood ; diagnosis ; Basigin ; metabolism ; Case-Control Studies ; Female ; Humans ; Male ; Matrix Metalloproteinase 3 ; blood ; Medicine, Chinese Traditional ; Middle Aged ; Monocytes ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; blood

OBJECTIVETo study the effect of progesterone on matrix metalloproteinase-3 (MMP-3) expression in neonatal rat brain after hypoxic-ischemia.

METHODSFollowed the hypoxic-ischemia of neonatal rat brain, Evans blue (EB) staining and transmission electron microscopy were used to detect the blood-brain barrier pathological changes on permeability. MMP-3 protein expression in cerebral cortex was measured with Western blot.

RESULTSTransmission electron microscopy results showed that the blood brain barrier in hypoxic-ischemic group changed significantly compare to progesterone group. EB staining results suggested that the blood-brain barrier permeability of hypoxic-ischemic group was significantly increased compared to sham-operated group (P < 0.01). The blood-brain barrier permeability in progesterone group was also decreased in comparison to that of hypoxic-ischemic group (P < 0.05). Western blot image analysis results indicated that MMP-3 protein expression in the hypoxic-ischemic group increased significantly than that in sham-operated group (P < 0.01), and the progesterone group was decreased significantly than that in hypoxic-ischemic group (P < 0.05).

CONCLUSIONProgesterone may reduce the blood-brain barrier damage by reducing MMP-3 expression. This might be one of the protective mechanisms in the hypoxic-ischemic brain injury.

Animals ; Animals, Newborn ; Blood-Brain Barrier ; physiopathology ; Hypoxia-Ischemia, Brain ; metabolism ; pathology ; physiopathology ; Matrix Metalloproteinase 3 ; metabolism ; Progesterone ; pharmacology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the possible correlation between atherosclerosis and chronic periodontitis by establishing an animal model of chronic periodontitis and atherosclerosis in Wistar rat.

METHODSSixty male Wistar rats were divided into four groups: A (control group), B (chronic periodontitis group), C (atherosclerosis group), D (chronic periodontitis accompany with atherosclerosis group). Every group was accepted the corresponding treatment. Animals were sacrificed after 12 weeks. The periodontal index, levels of serum total cholesterol (TC) and low-density lipoprotein (LDL), the concentration of TNF-alpha and matrix metalloproteinase (MMP-3) were examined. The severity of chronic periodontitis and atherosclerosis was quantified by histopathology. The date were statistically analyzed.

RESULTSThrough detection of periodontal tissue of experimental teeth, serum and histopathology, animal models were successful. Histopathologic observation revealed:obvious inflammation of periodontal tissue was observed in group B and D. Attachment loss level in group B [(137.86 +/- 28.39) microm] and D [(162.36 +/- 22.69) microm] was higher than that in group A [(4.26 +/- 1.07) microm] and C [(68.07 +/- 18.25) microm] (P < 0.05), and that in group C was higher than group A (P < 0.05). Atherosclerotic lesions of abdominal aorta were formed in group C and D. The level of TC, LDL in group C and D was higher than that in group A and B (P < 0.05), and that in group D was higher than group C (P < 0.05). Animals in group B and D showed higher level of TNF-alpha, MMP-3 in serum than that in group A and C (P < 0.05). There was no correlation between the level of MMP-3 and TC (P = 0.971) or LDL (P = 0.604).

CONCLUSIONSChronic periodontitis may be a risk factor and contribute to the pathogenesis of atherosclerosis. MMP-3 may be an independent risk factor of atherosclerosis exclude TC and LDL.

Animals ; Aorta, Abdominal ; Aortic Diseases ; etiology ; pathology ; Atherosclerosis ; etiology ; pathology ; Cholesterol ; blood ; Chronic Periodontitis ; complications ; pathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; Lipoproteins, LDL ; blood ; Male ; Matrix Metalloproteinase 3 ; blood ; Periodontal Index ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo assess the association between matrix metalloproteinase-3 (MM-3) gene polymorphisms and subtypes of ischemic stroke (IS) in northern Han Chinese population.

METHODSA total of 289 patients with acute IS (within 3 days after the onset, including 185 with large artery atherosclerosis (LAA) and 104 for small artery occlusion (SAO)) and 175 matched healthy controls were recruited for this case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequenc-based typing (SBT) was carried out to analyze 3 SNPs of the MMP-3 gene.

RESULTSAn incomplete linkage disequilibrium (LD) block was constructed with the 3 SNPs, and the distribution of genotypes of the 3 SNPs differed between the LAA group and controls in a dominant model: Carriers of 5A allele (5A5A+5A6A) of the rs3025058 locus were 1.72 times more susceptible to LAA stroke compared with carriers of 6A6A alleles (P=0.017, OR=1.72, 95% CI: 1.10-2.69), carriers of G alleles (GG+AG) of the rs522616 locus were 0.52 times more susceptible to LAA stroke compared with carriers of AA alleles (P=0.005, OR=0.52, 95% CI: 0.33-0.82), whilst carriers of A allele of the rs679620 locus were 1.55 times more susceptible to LAA stroke compared with carriers of GG alleles (P=0.042, OR=1.55, 95% CI: 1.01-2.37). However, no significant difference has been found between particular genotypes of such SNPs between SAO patients and controls (P> 0.05). Furthermore, 5A-A-A and 6A-A-A haplotypes were significantly more common in LAA group than the controls (P< 0.05), whilst 6A-G-G haplotype has been the opposite (P< 0.01).

CONCLUSIONOur study has demonstrated that serum MMP-3 level is significantly increased at acute stage of LAA as well as SAO type strokes. There may be an association of rs3025058, rs522616 and rs679620 of MMP-3 gene with susceptibility to LAA stoke in northern Han Chinese population.

Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Case-Control Studies ; Female ; Humans ; Ischemia ; blood ; enzymology ; ethnology ; genetics ; Male ; Matrix Metalloproteinase 3 ; blood ; genetics ; Middle Aged ; Polymorphism, Single Nucleotide ; Stroke ; blood ; enzymology ; ethnology ; genetics

OBJECTIVETo investigate the value of metalloproteinase-3 (MMP-3) levels in assessing efficacy of etanercept treatment in patients with ankylosing spondylitis (AS).

METHODSThe serum and synovial fluid levels of MMP-3 were measured by enzyme linked immunosorbent assay (ELISA) in 48 patients with AS in week 0, 6 and 12; and also measured in 30 serum samples and 10 synovial fluid samples from healthy controls.

RESULTSThe serum levels of MMP-3 in AS patients were significantly higher than those in controls. In AS patients, the MMP-3 levels in synovial fluid were significantly higher than those in serum levels. The serum MMP-3 levels in AS patients with peripheral arthritis were higher than those with exclusively axial involvement; while C-reactive protein (CRP) levels and erythrocyte sedimentation rate (ESR) did not differ between these 2 groups of AS. At week 6 and week 12 of etanercept treatment, the serum MMP-3 levels were significantly decreased (p<0.01) with the declining trend of ESR, CRP, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Bath Ankylosing Spondylitis Functional Index (BASFI) (all p<0.01). Before the etanercept treatment (week 0), serum levels of MMP-3 were correlated with ESR, CRP, BASDAI and BASFI (p<0.05). ESR was also correlated with CRP and BASFI, but not with BASDAI (r=0.361, P=0.071). At weeks 12, serum MMP-3 levels were still correlated with ESR, CRP and BASDAI (P<0.05), but not with BASFI (P=0.339); ESR was correlated with CRP, but not with BASDAI and BASFI. There was a significant correlation between BASDAI and BASFI (r=0.818,P=0.001).

CONCLUSIONSerum MMP-3 levels are closely related to disease activity and may serve as an useful indicator for efficacy of etanercept treatment in AS patients.

Adolescent ; Adult ; Aged ; Antirheumatic Agents ; therapeutic use ; Biomarkers ; blood ; Etanercept ; Female ; Humans ; Immunoglobulin G ; therapeutic use ; Male ; Matrix Metalloproteinase 3 ; blood ; Middle Aged ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Spondylitis, Ankylosing ; blood ; drug therapy ; Young Adult

OBJECTIVETo investigate the mechanism of Tougu Xiaotong Granula (TXG) on prevention and treatment of knee osteoarthritis.

METHODSFifty New Zealand rabbits were randomly divided into 6 groups. Except those in the normal control group, all the rabbits were replicated into knee osteoarthritis model using modified Hulth method. They were administered by gastrogavage once every day respectively with 100 ml of normal saline to the rabbits in the normal group and those in the model group, with 10 g of Zhuanggu Guanjie Pill to those in the control group, and 5 g, 10 g and 20 g of TXG to those in the three TXG tested groups (tested group 1, 2 and 3). The levels of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and metalloproteinase 3 (MMP-3) in joint fluid, the blood content of malondialdehyde (MDA) and nitric oxide (NO) absorbance as well as the SOD activity in synovia were observed.

RESULTSOverexpressions of IL-1, IL-6, TNF-alpha and MMP-3 in joint fluid, increased blood content of NO and MDA were shown in the 8th and 16th week, and decreased SOD activity in synovia was shown in the 16th week of the experiment in all the model rabbits, as compared to those in the normal group, the difference was significant respectively (P < 0.05 or P<0.01). After 8 weeks of treatment, the levels of IL-1, TNF-alpha, MMP-3, NO and MDA in the control group, tested group 2 and 3 were significantly different to those in the model group respectively (P < 0.05, P < 0.01), and significant difference was also shown in the comparisons of those indexes between the control group and the tested group 1 vs the tested group 3 (P < 0.05). As for the level of IL-6, significant difference was shown in comparisons of the model group with the control group, tested group 2 and 3 in the 8th and 16th week of the treatment (P < 0.05 or P < 0.01), also in comparison of the tested group 3 with the tested group 1 in the 8th week, and in that of the tested group 2 with the control group and the tested group 1 in the 16th week (P < 0.05).

CONCLUSIONTXG could effectively postpone the degeneration of cartilage through effectively inhibiting the biological effects of cytokines, MMP-3 and oxygen free radical.

Animals ; Cytokines ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Female ; Male ; Malondialdehyde ; blood ; Matrix Metalloproteinase 3 ; metabolism ; Nitric Oxide ; blood ; Osteoarthritis, Knee ; blood ; drug therapy ; metabolism ; Phytotherapy ; Rabbits ; Superoxide Dismutase ; metabolism

OBJECTIVETo analyze the distribution of matrix metalloproteinase-3 (MMP-3) genotype and its association with the blood pressure profiles in Guangzhou rural population.

METHODSThis study was conducted among 680 rural residents aged 40-70 years (including 314 men and 366 women) from 3 villages in an rural area of Guangzhou. The blood pressures of the subjects were measured and blood samples were collected for genotype analysis using polymerase chain reaction and direct sequencing of the MMP-3 gene promoter region to detect the 5 adenines (5A)/6 adenines (6A) polymorphisms.

RESULTSThe frequencies of MMP-3 genotypes 6A/6A, 5A/5A, and 5A/6A were 82.6%, 1.8% and 15.6% among these residents, respectively. The distribution of MMP-3 genotypes and allele frequencies showed no significant gender- or age-related variations. The men with different genotypes (6A/6A vs 5A/6A+5A/5A) did not show significant differences in blood pressure levels, whereas the women with 5A/6A+5A/5A genotypes had higher systolic and diastolic blood pressures than those with a 6A/6A genotype. The allele 5A was highly frequent in the hypertensive residents as compared with the normotensive residents.

CONCLUSIONSThe 6A homozygote is the predominant genotype of MMP-3 in Guangzhou rural population, which has a significantly lower proportion of 5A homozygote than the Western populations. The 5A allele is associated with a high risk of hypertension especially in women and may affect both systolic and diastolic blood pressures.

Adult ; Age Distribution ; Aged ; Alleles ; Blood Pressure ; China ; epidemiology ; Female ; Gene Frequency ; Genotype ; Humans ; Hypertension ; epidemiology ; genetics ; Male ; Matrix Metalloproteinase 3 ; genetics ; Middle Aged ; Risk Factors ; Rural Population ; Sex Distribution