Griffin Darvin J, Vicari Josh, Buckley Mark R, Silverberg Jesse L, Cohen Itai, Bonassar Lawrence J
Department of Biomedical Engineering, Cornell University, Ithaca, New York.
J Orthop Res. 2014 Dec;32(12):1652-7. doi: 10.1002/jor.22713. Epub 2014 Sep 5.
Osteoarthritis (OA) is a disease that involves the erosion and structural weakening of articular cartilage. OA is characterized by the degradation of collagen and proteoglycans in the extracellular matrix (ECM), particularly at the articular surface by proteinases including matrix metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs).(1) Degradation of collagen and proteoglycans is known to alter shear mechanical properties of cartilage, but study of this phenomenon has been focused on bulk tissue properties. The purpose of this study was to assess microscale cartilage damage induced by trypsin or collagenase using a technique to measure the local shear viscoelastic properties. Safranin-O histology revealed a decrease in proteoglycans near the articular surface after collagenase and trypsin digestions, with proteoglycan depletion increasing in time. Similarly, confocal reflectance micrographs showed increasing collagen degradation in collagenase treated samples, although the collagen network remained intact after trypsin treatment. Both treatments induced changes in shear modulus that were confined to a narrow range (∼400µm) near tissue surface. In addition, collagenase altered the total energy dissipation distribution by up to a factor of 100, with longer digestion times corresponding to higher energy dissipation. The ability to detect local mechanical signatures in tissue composition and mechanics is an important tool for understanding the spatially non-uniform changes that occur in articular cartilage diseases such as OA.
骨关节炎（OA）是一种涉及关节软骨侵蚀和结构弱化的疾病。OA的特征是细胞外基质（ECM）中胶原蛋白和蛋白聚糖的降解，特别是在关节表面被包括基质金属蛋白酶（MMPs）和具有血小板反应蛋白基序的解聚素和金属蛋白酶（ADAMTSs）在内的蛋白酶降解。（1）已知胶原蛋白和蛋白聚糖的降解会改变软骨的剪切力学性能，但对这一现象的研究一直集中在大块组织特性上。本研究的目的是使用一种测量局部剪切粘弹性特性的技术，评估胰蛋白酶或胶原酶诱导的微观软骨损伤。番红O组织学显示，胶原酶和胰蛋白酶消化后关节表面附近的蛋白聚糖减少，蛋白聚糖消耗随时间增加。同样，共聚焦反射显微镜图像显示胶原酶处理的样品中胶原蛋白降解增加，尽管胰蛋白酶处理后胶原网络保持完整。两种处理均诱导剪切模量变化，且局限于组织表面附近的狭窄范围（约400μm）。此外，胶原酶使总能量耗散分布改变高达100倍，消化时间越长，能量耗散越高。检测组织成分和力学中的局部力学特征的能力是理解诸如OA等关节软骨疾病中发生的空间不均匀变化的重要工具。
