Matrix metalloproteinase activity and prostaglandin E2 are elevated in the synovial fluid of meniscus tear patients

Abstract

Purpose Meniscus tears are a common knee injury and are associated with the development of post-traumatic osteoarthritis (OA). The purpose of this study was to evaluate potential OA mediators in the synovial fluid and serum of meniscus tear subjects compared to those in the synovial fluid of radiographic non-OA control knees. Materials and Methods Sixteen subjects with an isolated unilateral meniscus injury and six subjects who served as reference controls (knee Kellgren-Lawrence grade 0–1) were recruited. Twenty-one biomarkers were measured in serum from meniscus tear subjects and in synovial fluid from both groups. Meniscus tear subjects were further stratified by tear type to assess differences in biomarker levels. Results Synovial fluid total matrix metalloproteinase (MMP) activity and prostaglandin E2 (PGE2) were increased 25-fold and 290-fold, respectively, in meniscus tear subjects as compared to reference controls (p<0.05). Synovial fluid MMP activity and PGE2 concentrations were positively correlated in meniscus tear subjects (R=0.83, p<0.0001). In meniscus tear subjects, synovial fluid levels of MMP activity, MMP-2, MMP-3, sGAG, COMP, IL-6, and PGE2 were higher than serum levels (p<0.05). Subjects with complex meniscus tears had higher synovial fluid MMP-10 (p<0.05) and reduced serum TNFα and IL-8 (p<0.05) compared to other tear types. Conclusions Given the degradative and pro-inflammatory roles of MMP activity and PGE2, these molecules may alter the biochemical environment of the joint. Our findings suggest that modulation of PGE2 signaling, MMP activity, or both following a meniscus injury may be targets to promote meniscus repair and prevent OA development.

Relationship between T1rho magnetic resonance imaging, synovial fluid biomarkers, and the biochemical and biomechanical properties of cartilage

“…C2C was measured in the synovial fluid using an enzyme-linked immunosorbent assay (Ibex) that detects a neoepitope created by the cleavage of type II collagen by collagenases. Total MMP activity in the synovial fluid was measured using the quenched fluorogenic substrate Dab-Gly-Pro-Leu-Gly-Met-Arg-Gly-Lys-Flu (Sigma-Aldrich), as previously described (Backus et al, 2011; Carter et al, 2015; Liu et al, 2016; McNulty et al, 2009; Wilusz et al, 2008). …”

The role of transient receptor potential channels in joint diseases

“…Inflammatory cytokines are important regulators of these pain mechanisms and their presence is associated with inflammatory pain arising from articular joints and IVDs (Ito and Creemers, 2013;Wuertz et al, 2012;Zhang et al, 2013). Interleukin-1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α) contribute to disease progression and pain, by acting directly not only as nociceptive triggers, but also by inducing generation of other potentially nociceptive molecules, including nitric oxide and prostaglandin E (Liu et al, 2016;. IL-1β and TNF-α are secreted by cells of the immune system, such as macrophages, and by a variety of other cells types, including chondrocytes, annulus fibrosus (AF) and nucleus pulposus (NP) cells, regulating host responses to stress, inflammation, infection or trauma (Berenbaum, 2013;Johnson et al, 2015;Oda et al, 2004;Vo et al, 2016).…”

Ultrasound‐Guided Treatment of Extrusive Medial Meniscopathy: A 3‐Step Protocol

“…In addition to the mechanical disruption of the extruded fibrocartilaginous tissue through the needle movements (perforations), we speculate that the meniscal needling could allow the synovial fluid to flow from the parameniscal recesses into the pathologic fragment of the medial meniscus, promoting healing processes, reabsorption phenomena mediated by proteolytic enzymes contained in the synovial fluid itself, and disorganization of the intrameniscal tangle of neovessels and neonerves characterizing chronic degenerative meniscopathy. 17 Moreover, US guidance can readily provide prompt navigation for a safer intervention, 18 avoiding any complications with regard to bleeding (of medial genicular arteries) and neural injures (ie, medial genicular nerves and infrapatellar branches of the saphenous nerve).…”