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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=765243
• 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.

赛马是在特定部位发生的灾难性裂缝和关节变性。创伤后的骨关节炎。这个问题的问题和进步，有时是灾难性的，因为在临床上，由于微观和X光片无法检测到与马关节相关的问题由NSERC IC在血液中资助的研究反映了体内SCB的吸收，并且可以证明其作为生物标志物（测试）检测早期的SCB度假胜地。骨骼的特定于目前没有测试（生物标志物），可用于特定的监视器关系中的骨质碎屑，该计划的长期目标是开发了特定的诊断血清测试。 。椎间盘规格蛋白质的最先进的技术将是其他生物标志物，我们将成为检测过多的生物标志物，用于赛马液体中的下肢骨骼。在赛马中过度软骨下部分辨率的病原体构成的知识差距是进展。