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: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=737979
• 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.

赛马遭受灾难性的骨折和关节退化，发生在特定的网站。它们是由过度重复的比赛和训练创伤造成的。这个问题是一个重要的经济和福利问题。这些创伤应力性骨折通常发生在关节软骨（软骨下骨- SCB）下面的致密骨中，并可导致关节内骨折或创伤后骨关节炎。局灶性骨微损伤首先累积，然后招募消化骨的破骨细胞以去除受损的骨。然而，它们会造成局部溶解，这会进一步削弱骨骼并导致骨折。活性破骨细胞在该部位保留约2周。有一个很大的未满足的需要，即及早发现这个问题，以防止其发展，有时是灾难性的后果。目前在临床上很难做到这一点，因为早期损伤是微观的，X光片无法检测到它。我的研究计划，调查有关马关节的问题超过20年，将集中在赛马骨中过度的骨细胞活性对骨折和关节退化的贡献这一重要课题。我们之前的研究，由NSERC资助，已经铺平了道路，我们目前的假设，破骨细胞特异性产品在血液中反映马SCB吸收在体内，并可能证明价值作为生物标志物（测试）的早期过度SCB吸收的检测。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测量指标，并且在本提案的情况下，是由破骨细胞释放的蛋白质或分子或其骨降解，并且对该过程具有特异性。 目前还没有可用于特异性监测与早期SCB再吸收相关的马骨吸收活性的测试（生物标志物），这是本申请的主题。该项目的长期目标是开发一种马骨吸收活性的特异性诊断血清试验，以反映过度的临床前SCB吸收。这项测试可以允许其检测和/或通过早期定制运动计划来预防其进展，以保护骨骼。具体来说，我们将研究已知的和新的马破骨细胞活性的生物标志物在细胞培养中的释放。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，用于检测赛马体液中的过度软骨下骨吸收。该研究计划涉及马兽医学中一个新的，新兴的，重要的领域，有望缩小赛马过度软骨下骨吸收早期发病机制的知识差距，并防止其进展。