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: 10470892
• 负责人: X. Lucas Lu
• 金额: $ 34.38万
• 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/10470892
• 关键词: Adherence; Adult; Adverse effects; Age; 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; 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; 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; Proliferating; Recording of previous events; Records; Regulation; Research; Research Design; Retrospective cohort study; Swelling; Techniques; Testing; Therapeutic; Therapeutic Agents; Therapeutic Effect; Traumatic Arthropathy; Traumatic injury; United States Centers for Medicare and Medicaid Services; cartilage cell; cartilage degradation; cholesterol control; chondroprotection; cytokine; data warehouse; effectiveness evaluation; efficacy evaluation; efficacy testing; high risk; inhibitor; joint inflammation; joint injury; lipid metabolism; mechanical properties; mechanotransduction; mevalonate; mouse model; prenylation; prevent; protective effect; restraint; 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 人关节的创伤性损伤会导致软骨变性并导致创伤后骨关节炎。 现在，实际上很少有技术可以防止关节伤后软骨变性。 我们的研究发现，他汀类药物是一类美国人使用的药物来控制胆固醇 水平可以有效保护软骨免受各种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功效和机制。首先，使用 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 特拉华州人口。其次，使用体外细胞/组织培养模型，我们将确定软骨 - 他汀类药物的保护机制。第三，我们将使用动物测试他汀类药物预防PTOA的功效 型号。该项目的结果可以为我们为他汀类药物申请的临床试验提供理由 关节损伤的患者。该项目的长期目标是寻求FDA批准以重新利用 他汀类药物的联合治疗和PTOA预防。如果这个项目成功，它将立即增加 正处方4000万当前他汀类药物的使用者，尤其是那些患有骨关节炎风险的高风险 与关节伤害病史发生。

项目成果

Calcium signaling of primary chondrocytes and ATDC5 chondrogenic cells under osmotic stress and mechanical stimulation.

• DOI: 10.1016/j.jbiomech.2022.111388
• 发表时间: 2022-12
• 期刊: JOURNAL OF BIOMECHANICS
• 影响因子: 2.4
• 作者: Li, Wen;Zhou, Yilu;Han, Lin;Wang, Liyun;Lucas Lu, X
• 通讯作者: Lucas Lu, X

Osteocytic Pericellular Matrix (PCM): Accelerated Degradation under In Vivo Loading and Unloading Conditions Using a Novel Imaging Approach.

• DOI: 10.3390/genes13010072
• 发表时间: 2021-12-28
• 期刊: Genes
• 影响因子: 3.5
• 作者: Pei S;Wang S;Martinez JR;Parajuli A;Kirn-Safran CB;Farach-Carson MC;Lu XL;Wang L
• 通讯作者: Wang L