BONE REMODELING INHIBITION IN A CARTILAGE DAMAGE MODEL

描述（改编自申请人的摘要）：骨关节炎（OA）是 一种使关节软骨受损的衰弱状态， 最终引起疼痛并导致关节功能降低。 OA 涉及合成代谢和分解代谢事件，然而，对许多人来说， 这些事件在未知的。 它已经在人类和动物身上被证明， 模型，OA涉及软骨和软骨下骨的变化，但 问题在于两者之间的确切关系。 它有 有人认为，增厚（硬化）的软骨下骨 在关节处吸收力，因此，将更大的力传递到 上面的关节软骨会受损 软骨 OA（人类和动物模型）中发生的变化 比骨骼变化更好的特征。 申请人将使用 木瓜凝乳蛋白酶诱导兔软骨损伤模型建立 软骨下骨的变化以及这些骨变化之间的关系 关节软骨也会发生变化 形态生化分析 骨骼和软骨的研究将为研究 两者之间的关系。 在这个模型中，软骨下骨的变化是 控制（通过一种经证实的骨重建抑制剂，阿仑膦酸盐）和 问题是，软骨损伤会有什么影响？ 的 具体目的是：1）确定抑制效果 软骨下骨重塑，通过阿仑膦酸钠的作用， 高剂量木瓜凝乳蛋白酶损伤后覆盖AC; 2）描述 骨的选择体液代谢标志物的变化和水平， 木瓜凝乳蛋白酶损伤后的软骨，有和没有阿仑膦酸钠 治疗，并将这些变化与形态学外观， AC和软骨下骨在两个时间点;和3）描述 木瓜凝乳蛋白酶损伤后的软骨下骨形态，有或没有 阿仑膦酸钠治疗 工作假设是， 在兔OA模型中的骨重建将限制骨基质的降解， 覆盖关节软骨。

DESCRIPTION (Adapted from the Applicant's Abstract): Osteoarthritis (OA) is a debilitating condition in which the articular cartilage becomes damaged, eventually causing pain and leading to a reduction in joint function. OA involves both anabolic and catabolic events, however, the stimulus for many of these events in unknown. It has been shown in humans, and in animal models, that OA involves both cartilage and subchondral bone changes, but the question remains as to the exact relationship between the two. It has been suggested that a thickened (stiffened) subchondral bone is less capable of absorbing forces at the joint and, therefore, transmits greater force to the overlying articular cartilage, which becomes damaged. The cartilaginous changes occurring in OA (both in humans and in animal models) have been much better characterized than the bony changes. The applicant will utilize an establish a rabbit model of chymopapain-induced cartilage damage to study the subchondral bone changes and the relationship between these bone changes and the articular cartilage changes. Morphological and biochemical analysis of the bone and cartilage will set the baseline for the study of the relationship between the two. In this model, subchondral bone changes are controlled (by a proven bone remodelling inhibitor, alendronate) and the question is raised what will be the effect on the cartilage damage? The Specific Aims of the proposal are: 1) to determine the effect of inhibition of subchondral bone remodelling, through the action of alendronate, on the overlying AC after a high dose chymopapain injury; 2) to describe the changes and levels of select body fluid metabolic markers of bone and cartilage after a chymopapain injury, with and without alendronate treatment, and to correlate these changes with morphological appearance of the AC and subchondral bone at two time points; and 3) to describe the subchondral bone morphology after a chymopapain injury, with or without alendronate treatment. The working hypothesis is that the inhibition of bone remodelling in a rabbit model of OA will limit the degradation of the overlying articular cartilage.