Andrish, Ballock, Calabro, Derwin, Greenwald, Hascall, Iannotti, Knothe, Lefebvre, McDevitt

Basic Research in Arthritis and Prosthetic Performance

Arthritis Affects nearly 43 million Americans

Arthritis in its many forms is the leading cause of musculoskeletal disability in our country, according to the federal government. Arthritis and related conditions affect nearly 43 million Americans, or one in six, at a cost of about $65 billion in medical care. With the aging of baby boomers, an estimated 60 million Americans will be affected by arthritis by the year 2020.

Today, more than 20 million Americans have osteoarthritis, the most common form of arthritis. Most are older, but younger people can be affected too, particularly those who have had knee or hip injuries. The fact is, almost everybody will experience this problem if they live long enough.

Unfortunately, there are no cures or even effective early treatments for arthritis, but the need for effective prevention and treatment grows more important every day as our population ages.

Basic Research in Arthritis and Prosthetic Performance

The Orthopaedic Research Center contains a significant number of projects directly relevant to understanding arthritic diseases, to preventing their progression, and to repairing or replacing damaged tissue.

Chondrocytes, the cells in articular cartilages, are responsible for maintaining the structure of the matrix that protects the underlying bone and provides smooth surfaces for skeletal motions. Changes in chondrocyte biology with age or after an injury to the joint lead to progressive failure in maintaining the matrix, with eventual erosion and loss of tissue, the major cause of osteoarthritic diseases. Drs. R. Tracy Ballock (M.D., an orthopaedic surgeon) and Veronique Lefebvre (Ph.D.) study the basic biology of chondrocyte development, maturation and death. An understanding of how these processes are regulated is necessary to devise ways to delay or intervene with the degenerative progression of the tissue.

Inflammatory processes, as in rheumatoid arthritis, that release of enzymes such as proteases into the matrix can accelerate the destruction of the cartilage tissues. Dr. Vincent Hascall (Ph.D., Co-chair of the Center, Co-editor of the Many Faces of Osteoarthritis (see attached copy)) studies the changes in extracellular matrices that promote inflammatory responses, and Dr. Suneel Apte (M.B.B.S., D. Phil.) studies key proteases that can damage the matrix if they are not contained or properly regulated.

Injuries to the tendon/ligaments or meniscus of the knee predispose the patient to early onset of arthritis, often 10-15 years earlier than the average population. Drs. Joseph Iannotti (M.D., Ph.D., Chair of the Department of Orthopaedics, Co-chair of the Center) and Kathleen Derwin (Ph.D.) study the biology of tendon damage and repair, and Dr. Cahir McDevitt (Ph.D.) studies the biology and repair of the meniscus.

Bone underneath the articular cartilage remodels in response to the changes in the mechanics caused by degeneration of the cartilage tissue in arthritic diseases, and can accelerate the process. Drs. Ulf Knothe (M.D., an orthopaedic surgeon) and Melissa Knothe Tate (Ph.D.) study the biology of bone formation and remodeling, especially that which occurs in response to biomechanical stimuli.

Successful repair of damaged cartilage or bone involves the recruitment of stem cells from adjacent tissue or bone marrow. These cells have the potential to become chondrocytes or bone cells depending upon their environment. Failure to repair the tissue often results from a lack of such stem cells in the immediate vicinity of the damage. Drs. George Muschler (M.D., an orthopaedic surgeon) and Ronald Midura (Ph.D.) study the biology of stem cells from bone marrow and the periosteal tissue surrounding the bone. They have developed procedures for expanding them in culture and then implanting them in animal models to promote new bone and cartilage formation.

Replacement of damaged cartilage tissue in arthritic joints by tissue engineering approaches is a current objective in many centers. Dr. Anthony Calabro (Ph.D.) has developed a novel way to form a cartilage-like matrix around living chondrocytes that has mechanical properties similar to normal articular cartilage matrix. Dr. Anthony Miniaci (M.D., our newly appointed director of Sports Medicine in Orthopaedics) will now explore the use of the tissue-engineered matrix in clinical settings such as for young patients with cartilage defects.

Joint Replacement is the last-resort, but very effective treatment for arthritis. In some patients, however, the artificial joint components loosen or become infected, causing great pain. Center researchers are striving to understand the causes for these failures and identify biomarkers that can be used to predict who will succumb to this problem. (Arthritis Clinical Research in ORC)