Biomechanical, histologic and macroscopic assessment of articular cartilage in a sheep model of osteoarthritis
Biomechanical, histologic and macroscopic assessment of articular cartilage in a sheep model of osteoarthritis
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DOI：
10.1016/j.joca.2004.05.006
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发表时间：
2004-08-01
影响因子：
7
通讯作者：
Appleyard, RC
中科院分区：
文献类型：
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作者：
Oakley, SP;Lassere, MN;Appleyard, RC
目的：我们的主要目的是探索绵羊内侧半月板切除术(MMX)早期骨关节炎(OA)模型的全部潜力，以验证非破坏性关节软骨(AC)评估和治疗干预的有效性。我们的第二个目标是重新评估绵羊MMX术后不同类型AC之间的关系。方法：在4个正常关节和16个MMX绵羊窒息(膝关节)关节上，对所有6个关节面上的5437个参考点进行宏观评估、动态剪切模量(G*)、相位滞后和AC厚度测量。在这些点中的702个点，可以与组织学评估大体结构损伤、胶原组织(双折射)和蛋白多糖含量进行比较。结果：组织学大体结构损伤和蛋白多糖丢失贯穿整个关节，最严重的(纤颤)发生在MMX部位附近。AC(30%-50%)厚度增加，G*(30%-40%)减少(30%-40%)和胶原双折射强度(15%-30%)在整个关节更均匀地发生。只有当G*下降80%时，宏观软化才明显。G*与AC厚度(Rho=-0.47)、胶原组织(Rho=0.44)、大体结构损伤(Rho=-0.44)和蛋白多糖含量(Rho=0.42)相关。多变量分析显示，胶原组织对动态剪切模量的贡献(t=6.66)是蛋白多糖含量(t=3.21)的两倍。胶原组织(Rho=0.11)和蛋白多糖含量(Rho=0.09)与时相滞后的相关性很弱。结论：宏观评估对AC软化不敏感，提示关节镜评估AC状态也可能表现不佳。胶原蛋白的完整性对保持AC硬度(G*)比蛋白多糖含量更重要。MMX后整个关节的主要AC软化和增厚的发展表明，除了生物力学负荷的干扰外，还参与了非机械性(如蛋白质和生化)化学和细胞因子介导的过程。绵羊MMX模型提供了一种环境，可以在其中评估与OA的启动和进展相关的AC的频谱变化。(C)2004年国际骨性关节炎研究会。爱思唯尔有限公司出版。保留所有权利。
Objectives: Our primary objective was to explore the full potential of the ovine medial meniscectomy (MMx) model of early osteoarthritis (OA) for studies to validate non-destructive articular cartilage (AC) assessments and therapeutic interventions. Our secondary objective was to re-evaluate the relationships between the different types of AC assessment after MMx in sheep.Methods: Macroscopic assessments, dynamic shear modulus (G*), phase lag and AC thickness measurements were performed at a total of 5437 reference points on all six articular surfaces in four normal joints and 16 MMx ovine stifle (knee) joints. Comparisons with histologic assessments of gross structural damage, collagen organisation (birefringence) and proteoglycan content were possible at 702 of these points.Results: Histologic gross structural damage and proteoglycan loss were seen throughout the joint with greatest severity (fibrillation) in closest proximity to the MMx site. Increases in AC (30-50%) thickness, reductions in G* (30-40%) and collagen birefringence intensity (15-30%) occurred more evenly throughout the joint. Macroscopic softening was evident only when G* declined by 80%. G* correlated with AC thickness (rho = -0.47), collagen organisation (rho = 0.44), gross structural damage (rho = -0.44) and proteoglycan content (rho = 0.42). Multivariate analysis showed that collagen organisation contributed twice as much to dynamic shear modulus (t = 6.66) as proteoglycan content (t = 3.21). Collagen organisation (rho = 0.11) and proteoglycan content (rho = 0.09) correlated only weakly to phase lag.Conclusions: Macroscopic assessments were insensitive to AC softening suggesting that arthroscopic assessments of AC status might also perform poorly. Collagen integrity was more important for the maintenance of AC stiffness (G*) than proteoglycan content. The development of major AC softening and thickening throughout the joint following MMx suggested involvement of non-mechanical (e.g., protein and biochemical) chemical and cytokine mediated processes in addition to the disturbance in biomechanical loading. The ovine MMx model provides a setting in which the spectrum of AC changes associated with the initiation and progression of OA may be evaluated. (C) 2004 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.