An in vitro investigation to understand the synergistic role of MMPs-1 and 9 on articular cartilage biomechanical properties

Abstract

Matrix metalloproteinases (MMPs) play a crucial role in enzymatically digesting cartilage extracellular matrix (ECM) components, resulting in degraded cartilage with altered mechanical loading capacity. Overexpression of MMPs is often caused by trauma, physiologic conditions and by disease. To understand the synergistic impact MMPs have on cartilage biomechanical properties, MMPs from two subfamilies: collagenase (MMP-1) and gelatinase (MMP-9) were investigated in this study. Three different ratios of MMP-1 (c) and MMP-9 (g), c1:g1, c3:g1 and c1:g3 were considered to develop a degradation model. Thirty samples, harvested from bovine femoral condyles, were treated in groups of 10 with one concentration of enzyme mixture. Each sample was tested in a healthy state prior to introducing degradative enzymes to establish a baseline. Samples were subjected to indentation loading up to 20% bulk strain. Both control and treated samples were mechanically and histologically assessed to determine the impact of degradation. Young’s modulus and peak load of the tissue under indentation were compared between the control and degraded cartilage explants. Cartilage degraded with the c3:g1 enzyme concentration resulted in maximum 33% reduction in stiffness and peak load compared to the other two concentrations. The abundance of collagenase is more responsible for cartilage degradation and reduced mechanical integrity.

Anti-Inflammatory and Analgesic Effects of Schisandra chinensis Leaf Extracts and Monosodium Iodoacetate-Induced Osteoarthritis in Rats and Acetic Acid-Induced Writhing in Mice

“…IL-1β activates transcription factors via the MAPK and NF-κB signalling pathways to regulate inflammatory responses, resulting in the production of inflammatory mediators such as NO, PGE2, COX-2, and other catabolic factors that may accelerate cartilage degeneration [ 30 , 31 , 32 ]. Moreover, cytokines upregulate the gene expression of MMPs, which promotes the degradation of articular cartilage by breaking down proteoglycan, the main component of the ECM [ 33 , 34 ]. MMP-2 and MMP-9 are gelatinases that degrade a broad range of collagen and proteoglycans.…”

Knowledge mapping of autophagy in osteoarthritis from 2004 to 2022: A bibliometric analysis

“…Inflammasomes are inflammatory multiprotein complexes that can be assembled and activated in response to reactive oxygen species (ROS) or lysosomal destabilization, and are involved in inflammatory-based OA ( 23 ). The initiation of inflammasomes leads to the production of inflammatory cytokines, and stimulates increased release of cartilage degradation enzymes such as matrix metalloproteinase (MMP), causing ECM degradation ( 24 ). Excess degradation products are released into the synovial fluid, and become inflammatory mediators presented to T lymphocytes.…”

Anti-Inflammatory and Chondro-Protective Effects of Acidic Polysaccharide from Enteromorpha Prolifera in Experimental Models of Osteoarthritis In-Vitro and In-Vivo

“…MMPs as proteolytic enzymes, which play a key role in the degradation of articular cartilage, 26 making it a potential target for the OA treatment. The abundant expression of MMPs in joint disorders is largely due to their ability to degrade the extracellular matrix (ECM).…”