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 investigate the effects of prophylactic administration of all-trans retinoic acid (ATRA) in relieving inflammation in a rat model of collagen-induced arthritis (CIA).

METHODSFemale Wistar rats (6 to 8 weeks old) were randomly divided into normal control group, solvent control group, and prophylactic ATRA treatment (0.05, 0.5, and 5 mg/kg) groups. All the rats except for those in normal control group were subjected to subcutaneous injection of type II collagen and incomplete Freund adjuvant in the tails to induce CIA, followed by injection on the following day with saline, corn oil or different doses of ATRA 3 times a week. The arthritis index (AI) scores, histological scores, serum levels of TNF-α, IL-17A, and IL-10, and expressions of proteases related with cartilage damage were evaluated.

RESULTSOn the 15th day after the primary immunization, the AI scores increased significantly in all but the normal control groups; the scores increased progressively in all the 3 ATRA groups but remained lower than that in the solvent control group, which was stable over time. The rats in the 3 ATRA groups showed obvious pathologies in the knee and ankle joints, but the semi-quantitative scores of pathology damage showed no significance among them. Compared with those in solvent control group, the serum IL-17A and TNF-α levels decreased, serum IL-10 level increased, and the expressions of ADAMT-4 and MMP-3 proteins decreased significantly in the knees in the 3 ATRA groups.

CONCLUSIONATRA can reduce the production of TNF-α and IL-17A and increase the production of IL-10 to alleviate the inflammation in rats with CIA. ATRA may delay the progression of RA by correcting the imbalance of Th1/Th2 and Th17/Treg.

ADAMTS4 Protein ; metabolism ; Animals ; Arthritis, Experimental ; chemically induced ; drug therapy ; Collagen Type II ; Female ; Freund's Adjuvant ; Inflammation ; drug therapy ; Interleukin-10 ; blood ; Interleukin-17 ; blood ; Lipids ; Matrix Metalloproteinase 3 ; metabolism ; Rats ; Rats, Wistar ; T-Lymphocytes, Regulatory ; immunology ; Th17 Cells ; immunology ; Tretinoin ; pharmacology ; 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 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 investigate the anti-inflammatory effect of Herba Siegesbeckiae extracts on mouse rheumatoid arthritis induced by arthrogen-CIA monoclonal antibody.

METHODSThe rheumatoid arthritis was induced by arthrogen-CIA arthritogenic monoclonal antibody in mice. The sandwich enzyme-linked immunosorbent assay was used to determine the concentration of IL-1βin mouse serum,and the content of IL-6,IL-17 and MMP-3 in supernatant of tissue homogenate of hind limb below the stifle of mice. One-way ANOVA was used for data analysis.

RESULTSThe toe swelling was attenuated in Siegesbeckiae group than that in model group [(0.218 ± 0.0307)cm(3) compared with (0.2545 ± 0.0179)cm(3), P<0.05]. The serum IL-1β level in Siegesbeckiae group was lower than that in model group [(63.74 ± 21.74)pg/ml compared with (104.96 ± 31.22)pg/ml, P<0.01]. The contents of IL-6, IL-17 and MMP-3 in tissue supernatants of Siegesbeckiae group were all lower than those of model group [(171.10 ± 48.35)pg/ml compared with (249.64 ± 75.08)pg/ml, P<0.05; (115.42 ± 56.52)pg/ml compared with (208.40 ± 88.54)pg/ml, P<0.05;(3660.31 ± 1680.99) pg/ml compared with (5420.79 ± 1201.43)pg/ml, P<0.05, respectively].

CONCLUSIONThe extract of Herba Siegesbeckiae has anti-inflammatory effect on mouse rheumatoid arthritis induced by mixed arthrogen monoclonal antibody.

Animals ; Anti-Inflammatory Agents ; therapeutic use ; Antibodies, Monoclonal ; Arthritis, Experimental ; drug therapy ; Arthritis, Rheumatoid ; chemically induced ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Enzyme-Linked Immunosorbent Assay ; Interleukin-17 ; metabolism ; Interleukin-1beta ; blood ; Interleukin-6 ; metabolism ; Matrix Metalloproteinase 3 ; metabolism ; Mice ; Mice, Inbred BALB C

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

This study was conducted to determine if nasal salmon calcitonin has additional beneficial effects on clinical symptoms, serum NO, IL-1beta, matrix metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II) levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with exercise therapy. Fifty female patients with knee OA were randomized into two groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and a home exercise program; the second group (n = 20) received a home exercise program for 6 months. Compared with baseline,while significant improvements were observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20-m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first group, walking and resting VAS, and WOMAC physical function scores were improved (P = 0.029) in the second group after treatment. Significantly increased levels of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the area of medial femoral condyle (P < 0.05) were noted only in the first group. There were significant differences in VAS activation values (P = 0.032) and NO levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon calcitonin may have possible chondroprotective effects besides its known effects on symptoms in patients with knee OA.
Aged ; Bone Density Conservation Agents/*therapeutic use ; Calcitonin/*therapeutic use ; Collagen Type II/urine ; Exercise Therapy ; Female ; Humans ; Interleukin-1beta/blood ; Magnetic Resonance Imaging ; Matrix Metalloproteinase 3/blood ; Middle Aged ; Nitric Oxide/blood ; Osteoarthritis, Knee/*drug therapy/radiography ; Peptide Fragments/urine ; Respiratory Therapy ; Severity of Illness Index ; Treatment Outcome ; Walking

This study was conducted to determine if nasal salmon calcitonin has additional beneficial effects on clinical symptoms, serum NO, IL-1beta, matrix metalloproteinase 3, urinary C-terminal telopeptide type II collagen (CTX-II) levels and MRI findings in knee osteoarthritis (OA) when used concomitantly with exercise therapy. Fifty female patients with knee OA were randomized into two groups. The first group (n = 30) received 200 IU/day nasal salmon calcitonin and a home exercise program; the second group (n = 20) received a home exercise program for 6 months. Compared with baseline,while significant improvements were observed in visual analogue scale (VAS), WOMAC pain, physical function scores, 20-m walking time (P < 0.001) and WOMAC stiffness score (P = 0.041) in the first group, walking and resting VAS, and WOMAC physical function scores were improved (P = 0.029) in the second group after treatment. Significantly increased levels of serum NO and urinary CTX-II (P < 0.001) and significant improvements in the area of medial femoral condyle (P < 0.05) were noted only in the first group. There were significant differences in VAS activation values (P = 0.032) and NO levels (P < 0.001) in the favor of the first group. In conclusion, nasal salmon calcitonin may have possible chondroprotective effects besides its known effects on symptoms in patients with knee OA.
Aged ; Bone Density Conservation Agents/*therapeutic use ; Calcitonin/*therapeutic use ; Collagen Type II/urine ; Exercise Therapy ; Female ; Humans ; Interleukin-1beta/blood ; Magnetic Resonance Imaging ; Matrix Metalloproteinase 3/blood ; Middle Aged ; Nitric Oxide/blood ; Osteoarthritis, Knee/*drug therapy/radiography ; Peptide Fragments/urine ; Respiratory Therapy ; Severity of Illness Index ; Treatment Outcome ; Walking

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 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