At the Musculoskeletal Research Lab within the University of Kentucky Gluck Equine Research Center, in Lexington, we are committed to enhancing the welfare of horses and advancing the field of equine and translational sports medicine.  

As elite athletes, horses rely on their musculoskeletal systems to perform at peak levels, and dysfunctions in this system will affect their performance. Osteoarthritis (OA) is the most common cause of lameness in horses and is characterized by chronic inflammation and progressive degeneration of all articular tissues. The management of OA is a significant challenge for equine veterinarians, as available treatments fail to fully restore joint function. Successful management of OA hinges on a comprehensive understanding of the mechanisms that drive inflammatory degeneration of joints.  

Understanding the Two Sides of Inflammation  

Inflammatory events, including those involving joints, surge with the purpose of counteracting tissue damage, clearing tissue debris and driving tissue repair and recovery of joint health.  

The transition from acute inflammation towards recovery of joint health is called inflammation resolution. Such a process is not simply passive termination of inflammation, but one in which pro-inflammatory mediators are metabolized into those that resolve inflammation to recover joint health. Traditional treatments for OA typically aim to alleviate symptoms by suppressing inflammation (using NSAIDs or intra-articular corticosteroids), as well as mechanisms involved in the housekeeping of joint tissues. While widely used due to the power to suddenly stop inflammation, these methods offer significant temporary relief, but the lack of disease-modifying properties can ultimately accelerate disease progression. While such effects were thought to result only from certain intra-articular corticosteroids, it is currently known that by suppressing inflammation, all anti-inflammatory drugs can prevent the synthesis of these specialized pro-resolving mediators (SPMs), paradoxically setting the stage for chronic inflammation.  

Macrophages in Osteoarthritis  

Macrophages are immune cells in the joint and critical players in joint health and resolution of inflammation. Studies from our lab and collaborators have shown that in osteoarthritic joints, macrophages become overwhelmed and are unable to properly resolve inflammation. This failure to resolve inflammation contributes to the chronic nature of OA, causing ongoing damage to the joint.  

Interestingly, our team has also discovered that injecting autologous macrophages, derived from the horse’s own bone marrow, into inflamed joints can significantly aid in resolving inflammation. This approach not only mimics the natural process of inflammation resolution but does so in a way that restores joint health providing a more durable solution than traditional anti-inflammatory treatments. This method has shown promising results that are both comparable to corticosteroid injections and more effective in the long term without the side effects commonly associated with conventional treatments.  

Towards Pro-Resolving Therapies  

Our recent research focuses on identifying the mechanisms by which macrophages drive inflammation resolution and how we can harness these processes for therapeutic development. This includes recently completed in vitro and in vivo studies on PPAR-γ agonism in synovial tissues. Our team’s research utilizes point-of-care cell-based therapies and pro-resolving therapies that focus on enhancing the body’s own healing mechanisms. By targeting key pro-resolving cells and mediators, we hope to effectively treat chronic inflammation, and improve long-term equine joint health.  

Personal Reflection: A Journey in Research and Innovation  

As an equine surgeon with over 19 years of experience, I am honored to contribute to this critical research alongside my colleagues and mentors at the Gluck Equine Research Center. Under the mentorship of James MacLeod, VMD, PhD, and Bruno C. Menarim, DVM, PhD, I have gained invaluable insights into the complexities of osteoarthritis and the collaborative nature of scientific research. My postdoctoral program has strengthened both my clinical expertise and my ability to contribute meaningfully to the development of innovative treatments for equine OA. My career goals are to continually strive to push the boundaries of equine sports medicine. Our work is a testament to the power of teamwork and innovation in tackling some of the most pressing challenges in the field and I am humbled for being part of it. 

Editor’s note: This is an excerpt from Equine Disease Quarterly, Vol. 34, Issue 3, funded by underwriters at Lloyd’s, London, brokers, and their Kentucky agents. It was written by Guilherme M. M. van de Graaf, DVM, MSc, PhD Postdoctoral Scholar in the Musculoskeletal Research Lab at the University of Kentucky’s Gluck Equine Research Center, in Lexington.