CAN OSTEOCLAST BIOMARKERS DETECT EXCESSIVE SUBCHONDRAL BONE RESORPTION IN RACEHORSES?

赛马患有灾难性的骨折和关节退行性变，这些都发生在特定的部位。它们是由比赛和训练的过度重复创伤造成的。这个问题是一个重要的经济和福利问题。这些创伤性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，并可能导致关节内骨折或创伤后骨关节炎。局部骨骼微损伤首先积累，然后吸收消化骨骼的破骨细胞来移除受损的骨骼。然而，它们会造成局部溶解，从而进一步削弱骨骼并导致骨折。活跃的破骨细胞在这些部位停留大约2周。有一个巨大的未得到满足的需要，即及早发现这一问题，以防止其发展，有时还会产生灾难性的后果。目前在临床上很难在马身上做到这一点，因为早期的损伤是微观的，放射照片无法检测到它。*我的研究计划，调查了20多年与马关节相关的问题，将重点放在赛马骨中过度的破骨活动对骨折和关节退变的贡献这一重要主题。我们之前的研究由NSERC资助，为我们目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马在体内的SCB吸收，并可能被证明是检测早期SCB过度吸收的生物标志物(测试)的价值。生物标记物，或生物标记物，是疾病过程或治疗反应的可测量指标，在本提案中，是破骨细胞或其降解骨骼所释放的蛋白质或分子，对这一过程是特异的。*目前还没有可用的测试(生物标记物)来专门监测与本申请的主题--SCB早期吸收有关的马匹破骨活性。该计划的长期目标是开发一种针对马破骨细胞活性的特异性诊断血清测试，以反映临床前过度的SCB吸收。这种测试可以通过早期量身定做运动计划来检测和/或防止其进展，以保存骨骼。具体地说，我们将研究马破骨细胞活性的已知和新的生物标记物在细胞培养中的释放。然后，我们将使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记物。然后，我们将评估有希望的候选生物标志物，以检测赛马体液中过度的软骨下骨吸收。该研究计划致力于马兽医领域一个新的、新兴的、重要的领域，该领域有望弥合赛马软骨下过度吸收早期发病机制的知识空白，并防止其进展。**

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. **