Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, USA.
Osteoarthritis Cartilage. 2013 Aug;21(8):1132-41. doi: 10.1016/j.joca.2013.05.018. Epub 2013 Jun 6.
Current histological scoring methods to evaluate efficacy of potential therapeutics for slowing or preventing joint degeneration are time-consuming and semi-quantitative in nature. Hence, there is a need to develop and standardize quantitative outcome measures to define sensitive metrics for studying potential therapeutics. The objectives of this study were to use equilibrium partitioning of an ionic contrast agent via Equilibrium Partitioning of an Ionic Contrast-Microcomputed tomography (EPIC-μCT) to quantitatively characterize morphological and compositional changes in the tibial articular cartilage in two distinct models of joint degeneration and define localized regions of interest to detect degenerative cartilage changes.
The monosodium iodoacetate (MIA) and medial meniscal transection (MMT) rat models were used in this study. Three weeks post-surgery, tibiae were analyzed using EPIC-μCT and histology. EPIC-μCT allowed measurement of 3D morphological changes in cartilage thickness, volume and composition.
Extensive cartilage degeneration was observed throughout the joint in the MIA model after 3 weeks. In contrast, the MMT model showed more localized degeneration with regional thickening of the medial tibial plateau and a decrease in attenuation consistent with proteoglycan (PG) depletion. Focal lesions were also observed and 3D volume calculated as an additional outcome metric.
EPIC-μCT was used to quantitatively assess joint degeneration in two distinct preclinical models. The MMT model showed similar features to human Osteoarthritis (OA), including localized lesion formation and PG loss, while the MIA model displayed extensive cartilage degeneration throughout the joint. EPIC-μCT imaging provides a rapid and quantitative screening tool for preclinical evaluation of OA therapeutics.
目前用于评估潜在治疗药物对减缓或预防关节退化疗效的组织学评分方法耗时且为半定量性质。因此，需要开发和标准化定量结局指标，以确定研究潜在治疗药物的敏感指标。本研究的目的是使用离子对比剂的平衡分区（通过离子对比剂-微计算机断层扫描的平衡分区，EPIC-μCT）来定量描述两种不同关节退化模型中胫骨关节软骨的形态和组成变化，并定义局部感兴趣区域以检测退行性软骨变化。
本研究使用了碘酸钠（MIA）和内侧半月板横断（MMT）大鼠模型。手术后 3 周，使用 EPIC-μCT 和组织学分析胫骨。EPIC-μCT 允许测量软骨厚度、体积和组成的 3D 形态变化。
在 MIA 模型中，3 周后整个关节可见广泛的软骨退化。相比之下，MMT 模型显示出更局限的退化，内侧胫骨平台区域增厚，衰减减少，与蛋白聚糖（PG）耗竭一致。还观察到局灶性病变，并计算 3D 体积作为附加结局指标。
EPIC-μCT 用于定量评估两种不同的临床前模型中的关节退化。MMT 模型显示出与人类骨关节炎（OA）相似的特征，包括局灶性病变形成和 PG 丢失，而 MIA 模型显示整个关节广泛的软骨退化。EPIC-μCT 成像为 OA 治疗药物的临床前评估提供了快速和定量的筛选工具。
