‘One health’ is defined as a collaborative, multisectoral, and trans-disciplinary approach to the goal of achieving optimal health outcomes recognizing the interconnection between people, animals, and the environment. This concept has been applied successfully to leverage similarities in diseases shared by humans and domestic veterinary species to advance research and health outcomes for all species. We propose a ‘one medicine’ approach to investigate orthopedic disease—specifically, post-traumatic osteoarthritis (PTOA) secondary to: 1) cruciate ligament injury or 2) intra-articular fracture. Although rodent models have proven useful for studying basic mechanisms of disease, results from OA therapeutic trials in rodents and other experimentally-induced animal models often fail to translate to humans1. As genetically outbred species that share environments with humans, domestic veterinary species represent excellent spontaneous models of joint injury. Specifically, dogs frequently develop osteoarthritis secondary to rupture of the cranial cruciate ligament (RCCL)2, analogous to human anterior cruciate ligament (ACL) injury, and horses frequently develop osteoarthritis secondary to osteochondral fragmentation3, similar to human intra-articular fractures. The ultimate goal is to identify naturally occurring animal models that demonstrate similar biochemical and biophysical alterations as humans with PTOA in order to: 1) elucidate fundamental mechanisms of OA development/progression and 2) validate spontaneous models of OA for investigation of novel diagnostics and therapeutics. We will evaluate serum and synovial fluid biochemical parameters and metabolites and integrate this data with synovial fluid biophysical assessment, including synovial fluid microrheology and lubrication measurements. Similarities in veterinary and human patients could motivate veterinary clinical trials, with dual-species benefits.