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Osteoarthritis a Complex Disease with New Solutions

By Connie Raab

A multidisciplinary group of scientists has declared that osteoarthritis (OA), the most common form of arthritis, is "surprisingly complex," but has outlined a number of new approaches to its understanding, prevention and treatment. Their report, a review by 28 researchers at 17 academic and government institutions, cites over 250 published articles and is presented in two parts in the Annals of Internal Medicine. The effort was led by Dr. David T. Felson of Boston University and Reva C. Lawrence of NIAMS.

The disease, says the review, can result from an inherited predisposition to OA combined with a joint injury. Regular runners have almost no additional risk of OA, but football and soccer players and baseball pitchers are at increased risk. A healthy lifestyle helps — exercise can lessen disability if OA has developed. Strengthening the thigh muscles reduces risk of OA of the knee, as can losing weight. For people who have the disease, a combination of treatment approaches, including new medications and patient education, is effective.

The review points out that in the United States about 6 percent of adults over 30 have OA of the knee and about 3 percent have OA of the hip. The disease is responsible for more trouble walking and stair-climbing than any other disease, and it is the most common indication for total joint replacement of the hip and knee.

Development of the review was coordinated and funded by NIAMS and was based on a July 1999 conference at NIH cosponsored by the NIH Office of Disease Prevention, National Center for Complementary and Alternative Medicine, Office of Research on Women's Health, Office of Behavioral and Social Sciences Research, National Center for Medical Rehabilitation Research, NICHD, CDC, the Arthritis Foundation and American Academy of Orthopaedic Surgeons.

Molecular Mechanism Found for Impetigo

By Ray Fleming

The bacterium Staphylococcus aureus, cause of the common skin infection bullous impetigo, produces a toxin that attacks a protein highly specific for cell-to-cell binding in the outermost layer of the skin, according to a new study funded by NIAMS and reported in the November 2000 issue of the journal Nature Medicine. Breakup of this protein, say the researchers, not only brings about the characteristic blistering of the infection, but also gives the bacterium "an exquisitely specific mechanism to circumvent the skin's protective barrier and spread further."

The University of Pennsylvania's Dr. John Stanley and his colleagues there and at Japan's Keio University found that the toxin, exfoliative toxin A, causes impetigo's blisters when it breaks up the protein Desmoglein 1 (Dsg1), which is responsible for a specialized type of binding in epidermal skin cells. Only the Dsg1 protein is broken up, say the scientists, and not other closely related proteins. The consequent breakdown in skin cell adhesion gives Staphylococcus a way to proliferate and cause more damage.

The researchers suspected Dsg1 was the toxin's target because it is also the target of autoantibody attacks in pemphigus follaceus, a blistering skin disorder with similar cellular characteristics. The work was carried out in cell culture, mouse skin and with recombinant Dsg1, and the results emphasize the importance of the protein's functioning to healthy, protective skin. The major therapy for the infection will continue to be antibiotics, say the researchers, even though agents that fight protein breakup might help prevent the spread of the bacterium.

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