The UCSF Sports Medicine Group is devoted to increasing the understanding of many sports medicine and shoulder problems. The research performed ranges from basic science and stem cell research to clinical studies focusing on the outcomes of sports medicine and shoulder procedures. The group has published over 80 scientific papers, and has received grants from the American Orthopaedic Sports Medicine Society, the Orthopaedic Research and Education Foundation, and the NIH. With collaborations within the department and the University, the Sports Medicine Group is developing one of the strongest orthopaedic research programs in the country.
Cartilage Injury and repair
The distinctive physical properties of bone and cartilage are essential for their function in the skeleton. Cartilage withstands loads of up to ten times the weight of the body and endures approximately one million walking cycles per year. Nature’s engineering is at its best in bone, which is remodeled throughout life to help the body adapt to changing mechanical loads while resisting fracture. However, we have much to learn about the mechanisms by which bone and cartilage cells are directed to produce tissues with these remarkable physical characteristics.
Tamara Alliston, PhD, studies the crosstalk between biochemical and physical cues in the skeleton. Biochemical signals can direct stem cells to become cartilage cells or bone cells. The same signals can control the hardness and other physical features of the bone matrix. We investigate the mechanisms by which biochemical signals direct the differentiation of bone and cartilage cells, as well as how these signals specify the distinctive physical features of bone and cartilage matrix. We seek to understand how the physical features of bone and cartilage influence normal skeletal tissue function and how these features are disrupted in skeletal diseases such as osteoporosis and osteoarthritis. We apply what we learn in an effort to direct stem cells to repair skeletal tissues with the same biological and mechanical properties as healthy bone and cartilage.
The development of post-traumatic arthritis following intra-articular fracture (fractures that go through the joint) remains an unsolved problem facing orthopaedic surgeons. Hubert Kim, MD, PhD, is studying the role of programmed cell death, or apoptosis of the chondrocyte (cartilage cell), in the development of post-traumatic arthritis. His lab has discovered that high levels of chondrocyte apoptosis occur following fractures that go through the joint in humans. Currently, his research group is using a variety of techniques to identify specific regulators of apoptosis that may contribute to early cartilage degeneration following these complicated injuries. They have developed models of chondrocyte apoptosis and are using these models to study specific apoptosis pathways. Dr Kim’s group has found that a number of potential anti-apoptotic agents, including growth factors and caspase inhibitors, can block chondrocyte programmed cell death. Their ongoing studies are testing the hypothesis that these and other agents can be combined to more effectively limit chondrocyte loss and limit cartilage degradation, thereby leading to a better outcome following these injuries.
|Tissue engineered cartilage cells that have been grown in the laboratory and placed on a collagen scaffold for treatment of cartilage injuries
Alfred Kuo, MD, PhD is developing new tissue-engineering treatments for articular cartilage injuries. He is studying how stem cells form cartilage with the goal of improving this process. Through research sponsored by the Musculoskeletal Transplant Research Foundation, he is determining if stimulation with novel growth factors can lead stem cells to form better repair tissues.
Muscle Atrophy and Rotator Cuff Tears
Skeletal muscle atrophy has a profound impact on patients recovering from illness, injury, immobilization, and surgery. Among the most important factors in the cascade of events leading to muscle atrophy is activation of proteolytic enzymes that degrade extracellular matrix and basement membrane proteins. Recent studies have identified a critical role for matrix metalloproteinase (MMP)-2 in the pathobiology of muscle atrophy. However, the details of MMP-2 regulation due to muscle disuse remain undefined. Dr. Kim is currently evaluating the role of specific regulators of MMP-2 to determine what activates this pathway. Information gained from these experiments will provide us with a much more comprehensive understanding of MMP-2 regulation and function, and may lead to new therapeutic approaches for treating muscle atrophy after injury and/or immobilization by modulating atrophy-specific transcription factor binding.
Rotator cuff tears are one of the most common shoulder injuries, affecting up to 15% of the population over 60 years of age. Although small rotator cuff tears are easy to treat, large rotator cuff tears remain a difficult problem for the orthopaedic surgeon. In large rotator cuff tears, the muscle undergoes muscle atrophy and fatty infiltration, which is often irreversible at the time of repair. Dr. Kim and Brian Feeley, MD are investigating the pathways that are responsible in initiating muscle atrophy and fatty infiltration in large rotator cuff tears. The goal of the study is to define these factors and develop novel therapeutic treatments that can treat the muscle atrophy and fatty infiltration, leading to better outcomes following rotator cuff repair.
In collaboration with the musculoskeletal radiology imaging group at UCSF, the sports medicine faculty has developed innovative techniques to follow cartilage injuries following ACL reconstruction. Under the direction of C. Benjamin Ma, MD, current research focuses on using high resolution MRI to evaluate knee kinematics following ACL reconstruction and cartilage injury. Other research studies include evaluating patients with anterior knee pain with high resolution MRI to determine if there is early cartilage damage associated with the anterior knee pain.
Understanding how knee ligaments function is an important factor in determining how reconstructions are performed. Brian Feeley, MD received the 2009 AOSSM Young Investigator Award to evaluate the kinematics of different pediatric ACL reconstruction techniques. Other studies include evaluation of scapula anatomy as it relates to shoulder replacement, and rotator cuff repair biomechanics. Clinical Studies
Anthony Luke MD, director of the Human Performance Center, is evaluating factors associated with patella tendonitis. He has also performed studies looking at knee and cartilage health in marathon runners. Dr. Christina Allen is evaluating factors that are important in determining why some ACL reconstructions fail. The group also is active in multi-center prospective studies including the MOON study evaluating outcomes following ACL surgery and the MARS study, which is looking at factors related to outcomes following rotator cuff surgery.