Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses

SIMPLE SUMMARY: Osteoarthritis (OA) is a common condition affecting horses and humans. The role of the innate immune system in the pathogenesis and progression of OA has been increasingly recognized in recent years. This review examines the function of the innate immune system in perpetuating inflammation seen in OA, drawing important insights across species from animal models of OA and humans, and discusses therapeutic immune modulatory options currently available to manage OA. ABSTRACT: Osteoarthritis (OA) is a common condition with diverse etiologies, affecting horses, humans, and companion animals. Importantly, OA is not a single disease, but rather a disease process initiated by different events, including acute trauma, irregular or repetitive overload of articular structures, and spontaneous development with aging. Our understanding of the pathogenesis of OA is still evolving, and OA is increasingly considered a multifactorial disease in which the innate immune system plays a key role in regulating and perpetuating low-grade inflammation, resulting in sustained cartilage injury and destruction. Macrophages within the synovium and synovial fluid are considered the key regulators of immune processes in OA and are capable of both stimulating and suppressing joint inflammation, by responding to local and systemic cues. The purpose of this review is to examine the role of the innate immune system in the overall pathogenesis of OA, drawing on insights from studies in humans, animal models of OA, and from clinical and research studies in horses. This review also discusses the various therapeutic immune modulatory options currently available for managing OA and their mechanisms of action.