Matrix Metalloproteinase-9 Level in Synovial Fluid—Association with Joint Destruction in Early Rheumatoid Arthritis

Abstract

Background and objective: Matrix metalloproteinases (MMPs) are the key enzymes in the pathogenesis of cartilage and joint damage and potentially a new biomarker of the early erosive form of rheumatoid arthritis (RA). Firstly, the study aimed to compare the level of MMP-9 in plasma (PL) and synovial fluid (SF) of patients with RA and osteoarthritis (OA). Secondly, the goal was to examine the association of MMP-9 level in PL and SF with early erosive changes in RA, and finally, to determine the association of MMP-9 level with serological parameters of the disease (rheumatoid factor-RF and anti-citrulline protein antibodies-ACPA). Materials and Methods: A total of 156 subjects were involved in this study (84 patients with RA and 72 patients with OA, who were involved as a control group). MMP-9 level was measured in PL and SF of all subjects by the sandwich enzyme-linked immunosorbent assay (ELISA) method. Standard radiographs of the hands and feet were used to detect joint damage and classification into erosive or non-erosive RA. The Larsen score (LS) was used for the quantitative assessment of joint damage, and its annual change (∆ LS) was used to assess the radiographic progression of the disease. Results: MMP-9 level in PL and SF was significantly higher in RA compared to controls (PL: 19.26 ± 7.54 vs. 14.57 ± 3.11 ng/mL, p< 0.01; SF: 16.17 ± 12.25 vs. 0.75 ± 0.53 ng/mL, p < 0.001) as well as in SF of patients with erosive compared to non-erosive RA (18.43 ± 12.87 vs. 9.36 ± 7.72; p < 0.05). Faster radiographic progression was recorded in erosive compared to non-erosive early RA (11.14 ± 4.75 vs. 6.13 ± 2.72; p < 0.01). MMP-9 level in SF, but not in PL, significantly correlates with the radiographic progression in both erosive and non-erosive RA (ρ = 0.38 and ρ = 0.27). We did not find a significant association between RF and MMP-9 level in early RA, but the ACPA level significantly correlates with MMP-9 level in SF (r = 0.48). Conclusion: The level of MMP-9 in plasma and synovial fluid of patients with RA is significantly higher compared to patients with osteoarthritis. The level of MMP-9 in synovial fluid is significantly higher in erosive than non-erosive early RA. It is significantly associated with the radiographic progression of the disease and the level of anti-citrulline protein antibodies.

Anti-inflammatory and antiresorptive effects of acyl substitution chromone derivatives in experimental model of rheumatoid arthritis

“…Примером таких лекарственных препаратов, внедренных в клиническую практику, являются ингибиторы янус-киназ: тофацитиниб, пефицитиниб и упадацитиниб [20]. В тоже время препараты на основе малых молекул могут воздействовать на иные биомишени, которые опосредуют формирование патогенеза РА, например ММП [21].…”

Metalloproteinases between History, Health, Disease, and the Complex Dimension of Social Determinants of Health

“…Specific MP patterns can even predict that some patient populations may have a greater risk for certain complications compared to others, suggesting tailored follow-up programs. There is evidence of these applications with several diseases, such as cardiovascular disease (e.g., atrial fibrillation, aneurysms, chronic venous disease, venous thromboembolism, vascular ulcers), cancer (i.e., lung carcinoma, ovarian cancer), inflammatory diseases (i.e., rheumatoid arthritis), oral diseases (i.e., periodontal disease), proctologic diseases (i.e., hemorrhoids), infective diseases (i.e., COVID-19), and neurodegenerative diseases (i.e., Alzheimer's disease) [76][77][78][79][80][81][82][83][84][85][86].…”

Matrix metalloproteinases in rheumatoid arthritis and osteoarthritis: a state of the art review

“…A different study identified a significant correlation between ACPA and MMP-9 levels in synovial fluid compared to RF and MMP-9 level [ 88 ]. This highlighted the importance of the ACPA parameter over RF for diagnosis of early RA.…”