Mechanical stability and biological consequences of cracks in articular cartilage

关节软骨裂纹的机械稳定性和生物学后果

• 批准号: 9190479
• 负责人: Lena Bartell
• 金额: $ 4.36万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-15 至 2018-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9190479
• 关键词: Acute; Address; Adult; Affect; Anatomy; Apoptosis; Apoptotic; Appearance; Arthralgia; Arthritis; Arthroscopy; Basic Science; Benign; Biological; Biological Markers; Cartilage; Cell Death; Cell physiology; Cessation of life; Chondrocytes; Clinical; Clinical Trials; Complex; Deformity; Degenerative polyarthritis; Deterioration; Diagnosis; Disease; Early treatment; Engineering; Environment; Evolution; Functional disorder; Future; Goals; Health; Joints; Knowledge; Lead; Location; Measures; Mechanics; Methods; Microscopy; Mitochondria; Morphology; Necrosis; Orthopedics; Pain; Pathogenesis; Patients; Pattern; Physiological; Prevalence; Reactive Oxygen Species; Replacement Arthroplasty; Research; Risk; Scheme; Somatotype; Staging; Surface; Surgeon; Techniques; Testing; Thick; Time; Tissues; Trauma; acute symptom; arthropathies; articular cartilage; base; clinical application; clinical decision-making; diagnosis standard; disability; improved; insight; joint injury; joint loading; mitochondrial dysfunction; potential biomarker; respiratory; response; targeted treatment; therapeutic target

Osteoarthritis (OA), the most common form of arthritis, is a joint disease characterized by the degradation of articular cartilage. This disease is complex and dynamic, evolving over years or even decades to ultimately cause joint pain and dysfunction. OA affects over 27 million adults in the US, making it a leading cause of disability. Despite being the most common cause of disability in western nations, OA has no cure and few options for diagnosis or treatment. In the search for a treatment, the most critical knowledge gap involves understanding the pathogenesis of OA prior to converging on the late-stage disease state, which is characterized by pain, deformity, and dysfunction. Indeed, the current standard of diagnosis by late-stage radiographic changes and eventual treatment via arthroplasty has proven to be a “solution” that is far from ideal. Cracks in cartilage (i.e. breaks in the matrix) have strong potential to be one such early marker of pre-OA and increased OA risk. Cracks are often observed after joint trauma as well as in late-stage disease. Indeed, cracks are often considered when grading and classifying cartilage damage and OA progression. Recent basic-science studies have defined crack prevalence and morphology, mechanical thresholds for crack initiation, and bio-physiological changes after cracking. However, to be developed as a marker for pre-OA or to guide clinical decision-making, key questions about cracks must be answered. These questions range from basic-science research to clinical application. This proposal outlines two basic-science questions that enhance the fundamental understanding of the mechanical and biological consequences of cracks in cartilage and, in so doing, begin to test cracks as an important orthopedic biomarker. Specifically, it is unknown if existing cracks destabilize cartilage or predispose it to further biological degradation. Broadly, the applicants hypothesize that crack morphology can be used to distinguish between cracks that are benign verses cracks that indicate irrevocably damage cartilage. In this study, the applicants more specifically hypothesize that, when loaded above a threshold, cracks in cartilage will grow and induce peracute cellular deterioration. To address these knowledge gaps, this proposal has two specific aims: (1) Investigate the mechanical stability of cracks in cartilage and (2) Characterize the acute biological consequences of cracks in cartilage.

骨关节炎（OA）是关节炎的最常见形式，是一种以降解为特征的关节疾病 关节软骨。这种疾病是复杂而动态的，在数年甚至几十年中发展起来 引起关节疼痛和功能障碍。 OA在美国影响超过2700万成年人，这使其成为主要原因 残疾。尽管是西方国家最常见的残疾原因，但OA无法治愈，很少 诊断或治疗的选择。在寻找治疗时，最关键的知识差距涉及 在融合后期疾病状态之前，了解OA的发病机理，即 以疼痛，畸形和功能障碍为特征。实际上，当前的诊断标准是晚期的 事实证明，通过关节置换术进行的射线照相变化和事件处理已被证明是一种“解决方案” 理想的。软骨的裂缝（即矩阵中的断裂）具有强大的潜力，可以成为Pre-OA的早期标记 并增加了OA风险。联合创伤以及晚期疾病中经常观察到裂缝。的确， 在评分和分类软骨损伤和OA进展时，通常会考虑裂缝。最近的 基本科学研究定义了裂纹患病率和形态，裂纹的机械阈值 开裂后的起始和生物生理变化。但是，要开发为前OA或 指导临床决策，必须回答有关裂缝的关键问题。这些问题范围从 基本科学研究临床应用。 该提议概述了两个基本科学问题，以增强对 软骨中裂纹的机械和生物学后果以及这样做开始测试裂纹作为一种 重要的骨科生物标志物。具体而言，未知现有裂纹是否破坏软骨或易感性 它可以进一步降解。 广义上，申请人假设裂纹形态可用于区分裂缝 良性的经文裂纹表明无可撤销地破坏软骨。在这项研究中，申请人更具体地 假设在阈值以上加载时，软骨中的裂缝将生长并诱导peracute细胞 恶化。为了解决这些知识差距，该提议具有两个具体的目的：（1）调查 软骨中裂纹的机械稳定性和（2）表征裂纹的急性生物学后果 软骨。