CAN OSTEOCLAST BIOMARKERS DETECT EXCESSIVE SUBCHONDRAL BONE RESORPTION IN RACEHORSES?

破骨细胞生物标志物可以检测赛马过度的软骨下骨吸收吗？

• 批准号: RGPIN-2019-04966
• 负责人: Laverty, Sheila
• 金额: $ 5.03万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=691450
• 关键词: OSTEOCLAST; BIOMARKERS; DETECT; EXCESSIVE; SUBCHONDRAL

Racehorses are afflicted with catastrophic fractures and joint degeneration that occur at specific sites. They are caused by the excessive repetitive trauma of racing and training. This problem is an important economic and welfare issue. These traumatic stress fractures often arise in the dense bone, underlying the cartilage (subchondral bone- SCB), of the joints and can lead to intra-articular fracture or post-traumatic osteoarthritis. Focal bone microdamage first accumulates and then osteoclast cells, that digest bone, are recruited to remove the damaged bone. However, they create focal lysis, that can further weaken the bone and lead to fracture. The active osteoclasts remain in the sites for approximately 2 weeks. There is a great unmet need to identify this problem early to prevent its progression and sometimes catastrophic consequences. It is currently difficult to do so clinically in horses as the early damage is microscopic and radiographs cannot detect it. ***My research program, investigating questions related to equine joints for over 20 years, will focus on the important topic of the contribution of excessive osteoclastic activity in racehorse bones to both fractures and joint degeneration. Our prior studies, funded by NSERC, have paved the way to our current hypothesis that osteoclast-specific products in blood reflect equine SCB resorption in vivo and may prove of value as biomarkers (tests) for the detection of early excessive SCB resorption. A biomarker, or biological marker, is a measurable indicator of a disease process or response to a treatment and, in the case of this proposal, are proteins or molecules released by osteoclasts or their degradation of bone and are specific for this process. ***There is presently no test (biomarker) available to specifically monitor equine osteoclastic activity in relation to early SCB resorption, the subject of this application. The long term objective of the program is to develop a specific diagnostic serum test for equine osteoclastic activity that will reflect excessive, pre-clinical, SCB resorption. This test could permit its detection and/or prevent its progression by early tailoring of the exercise program to preserve bone. Specifically, we will study the release of known and novel biomarkers of equine osteoclast activity in cell cultures. We will then employ state of the art technology to discover specific proteins released by equine osteoclasts to discover new better biomarkers. We will then assess promising candidate biomarkers for the detection excessive subchondral bone resorption in racehorse body fluids. The research program addresses a novel, emerging, important field in equine veterinary medicine that holds the promise to close the knowledge gap on the early pathogenesis of excessive subchondral resorption in racehorses and prevent its progression. **

赛马患有灾难性裂缝和在特定部位发生的关节变性。它们是由赛车和训练过度重复创伤引起的。 这个问题是一个重要的经济和福利问题。这些创伤性骨折通常在致密的骨骼中出现，其基础是关节的软骨（软骨下骨），并可能导致关节内骨折或创伤后骨关节炎。 首先募集局灶性骨微塑料，然后募集破骨细胞，以去除受损的骨头。但是，它们会产生局灶性裂解，从而进一步削弱骨骼并导致骨折。活性破骨细胞在该地点保留大约2周。尽早确定这个问题以防止其进展，有时甚至是灾难性的后果。目前很难在马匹上进行临床上的临床，因为早期损害是显微镜，并且X光片无法检测到它。 ***我的研究计划，研究了与马关节有关的问题已有20多年的时间，将重点介绍赛马骨骼中过度骨化性活性的重要主题。 我们先前由NSERC资助的研究为我们当前的假设铺平了道路，即血液中的破骨细胞特异性产物反映了体内的SCB SCB吸收，并且可能证明有价值作为生物标志物（测试）以检测早期过度SCB的吸收。 生物标志物或生物标记物是疾病过程或对治疗的反应的可衡量指标，在此提案的情况下，是破骨细胞或骨骼降解的蛋白质或分子，并且是针对此过程的。 ***目前没有可用于专门监测与早期SCB吸收有关的测试（生物标志物）。 该程序的长期目标是开发特定的诊断血清测试，以反映出过度的，临床前的SCB吸收。该测试可以允许其检测和/或通过早期调整锻炼程序来保存骨骼的检测和/或防止其进展。 具体而言，我们将研究细胞培养物中马破骨细胞活性的已知和新型生物标志物的释放。然后，我们将采用最先进的技术来发现马破骨细胞释放的特定蛋白质，以发现新的更好的生物标志物。 然后，我们将评估有前途的候选生物标志物，以检测赛马体液中过度的软骨下骨吸收。 该研究计划介绍了马兽医医学中的一个新颖，新兴的，重要的领域，该领域有望弥补赛马中过度软骨下部吸收的早期发病机理的知识差距，并防止其进展。 **