A joint effort: How dogs contribute and benefit from the “One medicine” approach to osteoarthritis

Osteoarthritis is a joint disease characterized by cartilage breakdown, bone changes, and synovial inflammation. To successfully treat osteoarthritis, a multifaceted approach that targets the whole joint is necessary. The dog embodies a unique opportunity to pursue this approach, as dogs, just like humans, suffer from the consequences of osteoarthritis. This thesis describes a multidisciplinary approach involving developmental and stem cell biology. By studying growth plate biology in large and small breed dogs, i.e. Great Danes and Miniature Poodles respectively, we show the importance of TGF/BMP and Notch signaling in cartilage and bone development. Moreover, adult dog stem cells derived from multiple tissues, including the bone marrow, fat tissue and synovial membrane, were investigated to understand how their use in osteoarthritis treatment strategies can be optimized. We demonstrate that adult stem cells are highly influenced by their tissue origin, donor characteristics, and the disease state of the joint. Furthermore, this thesis studied the regenerative processes occurring during joint distraction, to gain insights for regenerative strategies. We found that the reduced joint loading during joint distraction results in increased cartilage breakdown. However, the production of regenerative signals during joint distraction combined with the return to normal loading after treatment, results in a switch towards a regenerative joint environment after joint distraction. As proof-of-concept joint distraction was successfully applied to treat a patient dog with end-stage osteoarthritis. In conclusion, integration of the performed studies adds to the knowledge that will benefit both humans and dogs suffering from osteoarthritis, in a “One Medicine” approach.