RESUMEN
Matrix metalloproteinases (MMPs) degrade the extracellular matrix (ECM) subsequently damaging cartilage and altering biomechanical properties. Collectively, MMPs cleave every ECM macromolecule. However, MMPs present complex substrate interactions and digest differing ECM components making it difficult to understand the individual role each MMP plays in cartilage degradation. To understand the combined impact MMPs have on cartilage biomechanical properties, MMPs from two subfamilies: collagenase and gelatinase were investigated. Three ratios of MMP-1 (c) and MMP-9 (g), c1:g1, c1:g0 and c0:g1 were considered. Cartilage plugs (n = 30) were collected from the femoral condyles of 3 bovine stifle joints. In groups of 10, samples were treated with MMP-1, MMP-9, or a combination. Samples were subjected to indentation loading up to 20% bulk strain and were assessed mechanically and histologically to determine the degradative impact. Young's modulus and peak load were compared between the control and degraded explants. In comparison to samples degraded by MMP-1 or MMP-9 individually, cartilage degraded with both enzymes resulted in a 9-15% greater reduction in stiffness and peak load. Individually, MMP-1 and MMP-9 have a minimum effect on cartilage micromechanical properties, but synergistically the two enzymes digest ECM components and a much greater degradative effect is observed.
Asunto(s)
Cartílago Articular , Animales , Cartílago Articular/patología , Bovinos , Colagenasas/metabolismo , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Metaloproteinasas de la Matriz/metabolismoRESUMEN
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.