For more than 40 years, I have conducted basic, translational, and clinical research directed toward advancing understanding the musculoskeletal tissues, injuries and diseases of these tissues and methods of restoring musculoskeletal function following injury or disease. As much as anything, my interest in connective tissue biology and pathophysiology, led me to choose Orthopaedic Surgery as a specialty. As I gained experience in Orthopedics it became clear to me that osteoarthritis (OA) was a common disabling disease that remained poorly understood – a lack of knowledge that has prevented discovering of methods of preventing or slowing the progression of the disease. This stimulated me to direct my efforts towards cartilage biology and the pathophysiology of OA. Recognizing that the two universal risk factors for OA are aging and joint mechanical overload or injury, along with my collaborators, I studied these factors; and, found that the two factors interact, that is, at least some of the aging changes in chondrocyte function mimic changes caused by mechanical overloading. An idea supported by the clinical evidence that increasing age increases the risk and shortens time of onset of post-traumatic osteoathritis (PTOA) after joint injuries. Over the last 15 years I have focused most of my research on discovering how mechanical overloading of synovial joints causes OA and how to prevent articular cartilage degradation due to excessive joint loading and injury. Recent major projects include studies of how joint overloading causes OA in humans and animals, and interventions that interrupt deleterious biologic responses to joint overloading. Through these studies, our research team of clinicians, biologists and bioengineers has identified cellular responses to joint overloading that cause progressive cartilage erosion and promising methods of preventing cartilage loss. Our most recent work shows that mechanically induced chondrocyte metabolic dysfunction has a critical role in the onset and progression of OA and that preventing this chondrocyte dysfunction in large animal models minimizes or prevents cartilage erosion following joint injury thereby preventing PTOA.