Upregulation of inducible nitric oxide synthase and nitrotyrosine expression in primary knee osteoarthritis.

BACKGROUND: To investigate nitrite and inducible nitric oxide synthase (iNOS) levels in the plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to determine protein nitrotyrosine in synovial tissue of OA patients. MATERIAL AND METHOD: Thirty patients and 30 healthy controls were recruited into the present study. Plasma and synovial fluid nitrite levels were measured using Griess reaction. Plasma and synovial fluid iNOS concentrations were analyzed by enzyme-linked immunosorbent assay. Nitrotyrosine was detected immunohistochemically in synovial tissue of OA patients. RESULTS: Plasma and synovial fluid nitrite concentration in the OA group were significantly higher than those in the healthy control group were (p = 0.007 and p = 0.012). Furthermore, plasma iNOS levels were significantly higher in the OA group than those in healthy control group were (p = 0.04). Moreover, nitrotyrosine was detected immunohistochemically in macrophages, synovial lining layer and synoviocytes of synovial tissue in the OA group. CONCLUSION: These findings indicate that reactive nitrogen species and nitrotyrosine-containing proteins may be involved in the joint destruction process, and play a potential role in the pathogenesis of knee osteoarthritis.

Oxidative stress, vitamin e, and antioxidant capacity in knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) is a chronic progressive degenerative joint disorder which is characterised by strongly age-related regressive changes in articular cartilage. The objective of this study was to evaluate oxidative stress and antioxidant parameters in plasma and synovial fluid of patients with primary knee osteoarthritis. MATERIAL AND METHODS: Thirty-five OA patients and 35 healthy controls were recruited for this study. Nitrite, malondialdehyde (MDA), vitamin E, Trolox Equivalent Antioxidant Capacity (TEAC), and Ferric Reducing Antioxidant Power (FRAP) levels in plasma and synovial fluid were determined. RESULTS: Plasma nitrite levels in OA patients were significantly higher than those in healthy controls (p = 0.037). Furthermore, plasma MDA levels were significantly higher in OA patients than those in healthy controls (p < 0.001). Moreover, plasma vitamin E levels in OA patients were significantly lower than those in healthy controls (p < 0.001). Synovial fluid vitamin E levels of OA patients were significantly lower than paired plasma samples (p < 0.001). The total antioxidant capacities, as were measured by TEAC and FRAP assays in plasma of OA patients, were significantly lower than those in healthy controls (p < 0.01). MDA concentrations were positively correlated with nitrite concentrations but they were negatively associated with vitamin E and TEAC levels in synovial fluid of OA patients. CONCLUSION: The increased plasma levels of nitrite and MDA and the decreased plasma levels of vitamin E, TEAC, and FRAP indicated that oxidative stress was present in OA patients. These findings suggest that oxidative stress plays a potential role in pathophysiology of knee osteoarthritis.

Association of MMP-3 (-1612 5A/6A) polymorphism with knee osteoarthritis in Thai population.

Osteoarthritis (OA) is a degenerative joint disorder resulting in destruction of articular cartilage, osteophyte formation, and subchondral bone sclerosis. In recent years, numerous genetic factors have been identified and implicated in causing osteoarthritis. One such genetic defect is a single nucleotide polymorphism at position -1612 of matrix metalloproteinase-3 (MMP-3) promoter region, known to lead to three possible genotypes, 5A/5A, 6A/6A, and 5A/6A. The purpose of this study was to investigate the association of MMP-3 -1612 5A/6A gene polymorphism with knee osteoarthritis in Thai population. Genotype distributions and allelic frequencies of MMP-3 -1612 5A/6A polymorphism were investigated in 200 participants (100 patients with knee osteoarthritis and 100 healthy controls). Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. There was no statistically significant difference between the groups with respect to genotype distribution (P > 0.05). The 5A allele frequency was indicated as 15.5 %, and 6A allele was as 84.5 % in OA patients, whereas it was 10-90 % in the control group. Accordingly, the present study has indicated that the -1612 5A/6A polymorphism genotypes of MMP-3 gene promoter do not play a role in the development of osteoarthritis in the Thai population.

Relationship of serum IL-6, C-reactive protein, erythrocyte sedimentation rate, and knee skin temperature after total knee arthroplasty: a prospective study.

Knee osteoarthritis is a common cause of severe pain and functional limitation. Total knee arthroplasty is an effective procedure to relieve pain, restore knee function, and improve quality of life for patients with end stage knee arthritis. The aim of this study was to investigate the inflammatory process in patients with primary knee osteoarthritis before surgery and in subsequent periods following total knee arthroplasty. A prospective study of 49 patients undergoing primary total knee replacements was conducted. The patients were evaluated by monitoring serum interleukin-6 (IL-6), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), knee skin temperature, and clinical status. Measurements were carried out preoperatively and postoperatively on day one and at two, six, 14, and 26 weeks during follow-up review in the knee clinic. The serum IL-6 and CRP were elevated on the first postoperative day but fell to preoperative values at two weeks postoperatively. Both returned to within the normal range by six weeks postoperatively. In addition, the postoperative ESR showed a slow rise with a peak two weeks after surgery and returned to the preoperative level at 26 weeks postoperatively. The difference in skin temperature between operated and contralateral knees had a mean value of +4.5°C at two weeks. The mean value decreased to +3.5°C at six weeks, +2.5°C at 14 weeks, and +1.0°C at 26 weeks. The difference in skin temperature decreased gradually and eventually there was no statistically significant difference at 26 weeks after surgery. A sustained elevation in serum IL-6, CRP, ESR, and skin temperature must raise the concern of early complication and may suggest the development of postoperative complication such as haematoma and/or infection.

Relationship of plasma and synovial fluid BMP-7 with disease severity in knee osteoarthritis patients: a pilot study.

The objective of this study was to investigate bone morphogenetic protein-7 (BMP-7) levels in both plasma and synovial fluid of patients with primary knee osteoarthritis (OA) and to determine their relationship to disease severity. Thirty-two patients with knee OA and 15 healthy subjects were enrolled in the study. Anteroposterior knee radiographs were taken to determine the disease severity of the affected knee. The radiographic grading of OA in the knee was performed using the Kellgren-Lawrence criteria. BMP-7 levels in the plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The mean plasma BMP-7 concentration of the knee OA patients was significantly higher compared with that of healthy controls (12.1 +/- 1.6 vs 3.5 +/- 0.9 pg/ml, P = 0.001). Although BMP-7 levels in plasma were higher with respect to paired synovial fluid samples, the difference was not statistically significant (12.1 +/- 1.6 vs 10.5 +/- 2.2 pg/ml, P = 0.3). Subsequent analysis showed that plasma BMP-7 levels significantly correlated with disease severity (r = 0.77, P < 0.001). Furthermore, the synovial fluid levels of BMP-7 also correlated with disease severity (r = 0.60, P < 0.001). In addition, plasma BMP-7 levels showed a positive correlation with synovial fluid BMP-7 levels (r = 0.71, P < 0.001). Overexpression of BMP-7 in plasma and synovial fluid is related to progressive joint damage in knee OA. These findings suggest that BMP-7 might serve as a biochemical parameter for determining disease severity in primary knee OA and could play a potential role in cartilage protection and repair of OA.