Bonassar L J, Frank E H, Murray J C, Paguio C G, Moore V L, Lark M W, Sandy J D, Wu J J, Eyre D R, Grodzinsky A J
Massachusetts Institute of Technology, Cambridge 02139.
Arthritis Rheum. 1995 Feb;38(2):173-83. doi: 10.1002/art.1780380205.
To determine the effects of stromelysin treatment on biochemical, histologic, and swelling characteristics of intact cartilage explants and to correlate these effects with changes in the functional physical properties of the tissue.
Bovine articular cartilage explants were cultured for up to 3 days in the presence or absence of recombinant human stromelysin (SLN). Damage to matrix proteoglycans and collagens was assessed and characterized by N-terminal sequencing and Western blot analysis, respectively. Explants were mechanically tested to assess the ability of the tissue to withstand cyclic and static compressive loads.
Treatment with SLN resulted in a time- and dose-dependent loss of proteoglycans from cartilage explants, with significant loss seen after 3 days of exposure to 20 nM SLN: Histology indicated that initial loss of proteoglycans occurred in regions near the tissue surface and proceeded inward with increasing time of SLN exposure. SLN treatment resulted in degradation of matrix collagen types IX and II, and a concomitant increase in tissue swelling. This matrix degradation resulted in severe alterations in functional physical properties of the tissue, including compressive stiffness. The initial, focal loss of proteoglycans that resulted from SLN treatment was most accurately detected with high-frequency streaming potential measurements.
Exposure of intact cartilage to SLN caused specific, molecular-level degradation of matrix molecules, which resulted in changes in the swelling behavior and marked deterioration of functional physical properties of the tissue.
确定基质溶解素处理对完整软骨外植体的生化、组织学及肿胀特性的影响，并将这些影响与组织功能物理特性的变化相关联。
牛关节软骨外植体在有或无重组人基质溶解素（SLN）的情况下培养长达3天。分别通过N端测序和蛋白质印迹分析评估和表征基质蛋白聚糖和胶原蛋白的损伤情况。对外植体进行力学测试，以评估组织承受循环和静态压缩负荷的能力。
用SLN处理导致软骨外植体中蛋白聚糖随时间和剂量依赖性丢失，暴露于20 nM SLN 3天后可见明显丢失：组织学表明，蛋白聚糖的初始丢失发生在组织表面附近区域，并随着SLN暴露时间的增加向内发展。SLN处理导致IX型和II型基质胶原蛋白降解，并伴随组织肿胀增加。这种基质降解导致组织功能物理特性发生严重改变，包括压缩硬度。用高频流动电位测量最准确地检测到SLN处理导致的蛋白聚糖初始局灶性丢失。
完整软骨暴露于SLN会导致基质分子发生特定的分子水平降解，进而导致组织肿胀行为改变和功能物理特性明显恶化。
