The Role of Bone Resorption in Bone Marrow Lesions

7.项目摘要 骨中的局灶性变化，称为骨髓病变（BML，有时称为“骨挫伤”或“骨损伤”）。 “骨髓水肿模式”）在松质骨中使用磁共振成像观察到， 与关节退化有关在多项纵向研究中，骨的存在和/或增大 骨髓病变先于软骨退化，这表明， 骨髓病变影响关节健康。这些发现和其他发现表明， 可以解决长期存在的临床需要的指标骨关节炎，是目前不可逆的 关节退化理解骨髓病变的病理生理学的一个关键障碍是， BML中骨生理学的变化尚不清楚，因为唯一可用的组织病理学 BML是在全关节置换术时从人类身上采集的，此时关节退行性变已充分确立。 因此，很少有人知道骨髓病变的早期，可逆的阶段。为了解决这一关键障碍，我们 已经开发了一种兔模型，其中机械负荷在体内诱导骨髓损伤。在 建议的工作，我们使用这个新的模型系统，以了解机制，导致启动和 骨髓损伤的持续发展。我们的总体假设是，机械负荷刺激 松质骨中的骨吸收，导致BML的发生，随后导致 分解代谢骨关节串扰在拟议的探索/开发项目中，我们使用了新型兔子 模型，以解决骨吸收是启动和持续发展所需的假设 骨髓损伤的症状这项工作有一个单一的目标，有两个部分：目标1a）确定抑制的影响， 骨吸收对骨髓损伤的起始作用; Aim 1b）确定抑制骨吸收的作用 在建立骨髓损伤后的吸收。拟议的工作将决定贡献者的 骨髓病变的病理生理学，并测试抑制骨吸收的治疗可以 中断骨髓病变的开始或持续发展。

7. PROJECT SUMMARY Focal changes in bone, known as bone marrow lesions (BMLs, sometimes referred to as “bone bruise” or “bone marrow edema patterns”) are observed in cancellous bone using magnetic resonance imaging and are associated with joint degeneration. In multiple longitudinal studies the presence and/or enlargement of bone marrow lesions precedes cartilage degeneration, suggesting that alterations in bone physiology within a bone marrow lesion influence joint health. These findings and others suggest that bone marrow lesions may address the long-standing clinical need for an indicator of osteoarthritis that is present before irreversible joint degeneration. A critical barrier to understanding the pathophysiology of bone marrow lesions is that the changes in bone physiology within a BML are not understood because the only available histopathology of BMLs are taken from humans at the time of total joint replacement when joint degeneration is well established. Hence little is known about bone marrow lesions at early, reversible stages. To address this critical barrier, we have developed a rabbit model in which mechanical loading induces bone marrow lesions in vivo. In the proposed work we use this new model system to understand the mechanisms leading to the initiation and sustained development of a bone marrow lesion. Our global hypothesis is that mechanical loading stimulates bone resorption in cancellous bone that leads to the initiation of a BML which subsequently contributes to catabolic bone-joint crosstalk. In the proposed Exploratory/Developmental project we use the novel rabbit model to address the hypothesis that bone resorption is required for the initiation and sustained development of a bone marrow lesion. The work has a single Aim with two parts: Aim 1a) Determine the effects of inhibiting bone resorption on the initiation of a bone marrow lesion; Aim1b) Determine the effects of inhibiting bone resorption after a bone marrow lesion is established. The proposed work will determine contributors to the pathophysiology of bone marrow lesions and also test the idea that treatments that inhibit bone resorption can interrupt the initiation or sustained development of a bone marrow lesion.