Matrix Metalloproteinases-3 Baseline Serum Levels in Early Rheumatoid Arthritis Patients without Initial Radiographic Changes: A Two-Year Ultrasonographic Study

Abstract

Objective: To investigate the association of high baseline serum levels of metalloproteinases-3 (MMP-3) with structural damage to hand and feet joints, assessed by ultrasonography (US), in patients with early, treatment-naïve rheumatoid arthritis (RA), without initial X-ray-visible erosions, during 24 months follow-up. Methods: Sixty-three early RA (European League Against Rheumatism/American College of Rheumatology 2010), disease-modifying anti-rheumatic drugs/glucocorticoid naïve patients (mean age 53.4 ± 14.1) with symptom duration ≤12 months, had baseline serum levels of MMP-3 tested. OMERACT US group definition was used to detect the presence, as well as longitudinal diameter of erosions by US at study entry and after 24 months, at the level of wrists, metacarpophalangeal (MCP2/MCP5) joints of both hands, and fifth metatarsophalangeal joints. Results: Complete data were collected from 52 out of 63 patients. High baseline serum levels of MMP-3 (MMP-3-positive) were found in 46/63 patients. 122 bone erosions in total (1.9 bone erosions/patients) were detected by US at baseline visit and 213 erosions (4.3/patients) after 24 months. MMP-3 positive patients had significantly higher total number of erosions than MMP-3-negative (p = 0.039) and higher increase in size of bone erosions in the feet but not in the hand joints after follow-up (OR 4.82 [1.23–18.9], p = 0.024; OR 1.17 [0.320–4.26], p = 0.816 respectively). Conclusion: After 2 years of follow-up, US assessment showed a higher number of new bone erosions in MMP-3-positive compared to MMP-3-negative patients with early RA and no visible initial radiographic changes. High baseline levels of MMP-3 predict significantly higher structural damage progression at the level of feet, but not at the level of hand joints.

Serum matrix metalloproteinase-3 levels monitor the therapeutic efficacy in Syrian patients with rheumatoid arthritis

“…The focal cells that produce MMP-3 are chondrocytes, synovial fibroblasts, and monocytes as a result of the effect of inflammatory cytokines [ 14 ]. It has been proposed that levels of serum MMP-3 correlate with levels formed in the synovium [ 19 , 20 ]. In adult rheumatoid arthritis (RA), MMP levels are increased in both the synovial fluid and serum and are associated with joint damage [ 21 ].…”

Clinical application of MMP-3 in evaluating bone erosion in gouty arthritis

“…MMP-3 is considered to be a biomarker re ecting local joint in ammation [23] , and high levels of MMP-3 can be used as a predictor of joint destruction [24] . In pathological conditions, excessive activation of MMP -3 leads to a large number of cartilage degradation and subsequent bone erosion formation [23] , which is especially closely related to cartilage destruction and bone erosion in RA patients. MMP-3 is widely used as an in ammatory marker in a variety of diseases [14,19,25] , especially as a marker of bone erosion in the assessment of RA disease activity in clinical practice.…”

Bioresponsive Cytokine Delivery Responding to Matrix Metalloproteinases

“…However, the early stage of RA in humans is dominated by increased levels of MMP-1 and MMP-3 . Especially MMP-3 is elevated, and elevated MMP-3 levels correlate with structural damage and disease activity. , MMP-3 levels stay elevated in the middle stage of RA. They are reported to decrease in the advanced stage, possibly reflecting MMP-3’s role in the initiation and progression of cartilage destruction .…”

“…Sequential changes in synovial MMP expression levels in rheumatoid arthritis patients. The source data were taken from literature. ,,− …”

“…In early and middle RA, clocking IL4 release to MMP-3 might be attractive due to the association of MMP-3 levels with structural damage and disease activity (Figure ). , In late RA, IL4 release could be controlled by MMP-8, -9, or MT-1-MMP (MMP-14) or a protease-sensitive linker that is susceptible to all of the mentioned proteases, which could be enabled by reported overlapping substrate specificities of the mentioned MMPs (Figure ). In MI, the IL4 release clocked to the MMP-9 expression profile opens an interesting opportunity (Figure ).…”