Overview
The Center for Musculoskeletal Disease Research is a Center of Biomedical Research Excellence (COBRE) at UAMS funded by the National Institute of General Medical Sciences (NIGMS). The CMDR is a multidisciplinary center that encompasses a broad area of musculoskeletal research, including osteoporosis, orthopedics, biomechanics, multiple myeloma, and cancer metastases to bone, osteoarthritis, osteomyelitis, and aberrant skeletal development. The long-range goal of the Center is to establish the scientific foundation for sustained excellence in musculoskeletal research in central Arkansas. One important component of this effort is to fund pilot projects as a means of supporting the efforts of musculoskeletal investigators to pursue extramural funding. More information on how the CMDR is structured, our core facilities, and services can be obtained on our website or by contacting the CMDR Director, Dr. Charles O’Brien at caobrien@uams.edu.
Projects
Sanja Novak, Ph.D.
Assistant Professor, Physiology and Cell Biology
Osteoarthritis (OA) is a degenerative joint disease affecting more than 630 million adults worldwide and more than 32.5 million patients in the USA. OA is characterized by cartilage destruction, local inflammation, joint stiffness and pain, leading to a loss of joint function. In addition to aging and obesity, the athletes, military service members, law enforcement personnel, and fire fighters are exposed to significant risk factors for OA. Currently, OA treatments are restricted to decreasing pain and inflammation, and at advanced stages joint replacement surgery. Articular cartilage is an avascular tissue; however, the surrounding synovial space is highly vascularized, providing nutrients and oxygen to chondrocytes. In OA, the subchondral bone thickens, blood vessels infiltrate subchondral sites of articular cartilage, and synovitis and angiogenesis occur within the synovial membrane. It remains unclear what changes occur in the microvasculature of the synovial space during the early stages of OA and whether microvascular damage contributes to disease onset. Structural changes in the articular cartilage, including blood vessel infiltration and increased vascularity of the subchondral bone, are observed in advanced OA. However, damage to synovial blood vessels as a contributing factor in OA pathogenesis has not been well explored. Our proposal aims to evaluate the role of the synovial microvasculature in the development of OA.
We hypothesize that the loss of microvascular integrity within the joint is a triggering factor for OA. We propose to examine how vascular damage within the joint affects articular cartilage and contributes to OA progression. Our specific questions are: 1) Does mechanical stress-induced injury affects synovial microcirculation leading to articular cartilage damage; 2) Is OA pathology initiated by damage to the joint microvasculature; and 3) Do permeable blood vessels accelerated OA development following joint trauma?
Evaluating direct role of vasculature and its integrity within knee joint we will determine whether vascular changes noticed within the OA joint are the consequence of an osteoarthritis or the cause. Understanding these mechanisms may lead to novel therapeutic approaches for osteoarthritis treatment.