Prevention of PTOA via regulation of the cytomechanics of chondrocytes

通过调节软骨细胞的细胞力学预防 PTOA

• 批准号: 10687673
• 负责人: X. Lucas Lu
• 金额: $ 17.4万
• 依托单位: UNIVERSITY OF DELAWARE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687673
• 关键词: Adherence; Adult; Adverse effects; Animal Model; Big Data; Calcium Signaling; Cartilage; Cartilage Matrix; Case-Control Studies; Cell Cycle; Cells; Cellular Morphology; Cholesterol; Chondrocytes; Chronic; Clinical; Clinical Research; Clinical Trials; Cohort Studies; Conflict (Psychology); Cytoskeleton; Data Analyses; Data Set; Databases; Degenerative polyarthritis; Delaware; Development; Drug Prescriptions; Drug usage; Effectiveness; Europe; Extracellular Matrix; Family; Future; Goals; Healthcare Systems; Human; Hypertrophy; In Vitro; Inflammation; Interruption; Joints; Knee; Knowledge; Lead; Low Prevalence; Mechanics; Modeling; Musculoskeletal Diseases; Natural regeneration; Non-Steroidal Anti-Inflammatory Agents; Oral Administration; Outcome; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Pharmaceutical Solutions; Pharmacologic Substance; Phenotype; Pilot Projects; Plasma; Population; Population Control; Prevention; Recording of previous events; Records; Regulation; Research; Research Design; Retrospective cohort study; Swelling; Techniques; Testing; Therapeutic; Therapeutic Agents; Therapeutic Effect; Traumatic injury; United States Centers for Medicare and Medicaid Services; cartilage cell; cartilage degradation; cholesterol control; cytokine; data warehouse; effectiveness evaluation; efficacy testing; high risk; inhibitor; joint inflammation; joint injury; lipid metabolism; mechanical properties; mechanotransduction; mevalonate; mouse model; prenylation; prevent; protective effect; rho; rho GTP-Binding Proteins; subchondral bone; tissue/cell culture

PROJECT SUMMARY Traumatic injuries in human joints can cause cartilage degeneration and lead to post-traumatic osteoarthritis. Few techniques are now available in practice to prevent the cartilage from degeneration after the joint injuries. Our research discovered that statins, a class of drugs used by 40 million US people to control the cholesterol levels, can effectively protect the cartilage from various OA-inducing factors. We found that statins can directly act on the cartilage cells and prevent them from degrading the cartilage matrix. In this project, we will determine the efficacy and mechanism of statins for the prevention of post-traumatic osteoarthritis. First, using a retrospective cohort study, we will determine the correlation between statin use and OA occurrence among the Delaware population. Second, using in vitro cell/tissue culture models, we will identify the cartilage- protective mechanisms of statin. Third, we will test the efficacy of statin for PTOA prevention using animal models. Outcome of this project can provide us justifications for the clinical trials of statin application on the patients with joint injuries. The long-term goal of this project is to pursuit an FDA approval for the repurpose of statins in joint treatment and PTOA prevention. If this project is successful, it will immediately increase the prescription adherence of 40 million current statin users, especially those at a high risk of osteoarthritis occurrence with a joint injury history.

项目摘要 人类关节的创伤性损伤可导致软骨退化并导致创伤后骨关节炎。 在实践中，很少有技术可以防止关节损伤后软骨的退化。 我们的研究发现，他汀类药物，一类药物用于40万美国人控制胆固醇 水平，可以有效地保护软骨免受各种OA诱导因素的影响。我们发现他汀类药物可以直接 作用于软骨细胞并防止它们降解软骨基质。在这个项目中，我们将 确定他汀类药物预防创伤后骨关节炎的疗效和机制。首先利用 一项回顾性队列研究，我们将确定他汀类药物使用与OA发生之间的相关性， 特拉华州的人口。其次，使用体外细胞/组织培养模型，我们将鉴定软骨- 他汀的保护机制第三，我们将使用动物实验来测试他汀类药物预防PTOA的功效。 模型本项目的结果可为他汀类药物应用于临床试验提供依据。 有关节损伤的患者。该项目的长期目标是寻求FDA批准， 他汀类药物联合治疗和PTOA预防。如果这个项目成功，它将立即增加 4000万目前他汀类药物使用者的处方依从性，特别是那些骨关节炎高危人群 有关节损伤史。