By Peter Winter

BioWorld International Correspondent

OTTAWA, Ontario - An activated immune system can play a critical role in bone physiology. This discovery, published in the Nov. 18 issue of the journal Nature, may lead to the prevention and treatment of bone loss in arthritis.

According to the paper's lead author, Josef Penninger, an immunologist at Princess Margaret Hospital and the Amgen Research Institute, and a member of the departments of Medical Biophysics and Immunology at the University of Toronto, this could be a seminal paper on the finding that inflammation can trigger the body's T cells to inadvertently cannibalize its own bone, leading to severe bone degeneration and debilitating pain. It paves the way for future research into preventing the onset and progression of bone erosion in arthritis and the prevention of osteoporosis associated with many different kinds of diseases.

The research, funded by the Amgen Research Institute, was a collaborative effort between Penninger and his colleague Young-Yun Kong in Toronto, and Ulrich Feige and Bill Boyle at Amgen in Thousand Oaks, Calif. It marks the first time a research team has clearly identified the molecular cause of the bone and cartilage deterioration characteristic of many inflammatory diseases.

The trigger appears to be the tumor necrosis factor family molecule osteoprotegrin ligand (OPGL). Researchers found that activated T cells can directly influence osteoclastogenesis through OPGL. In a T-cell-dependent model of rat adjuvant arthritis characterized by severe joint inflammation, bone and cartilage destruction, they were able to demonstrate that blocking OPGL through osteoprotegerin treatment at the onset of disease prevents bone and cartilage destruction but not inflammation.

The results from these animal studies also appear to correlate well in humans. Penninger and his team found that, without exception, all the osteoarthritis and rheumatoid arthritis patients they examined expressed OPGL in their joints.

When the body is attacked by a virus or bacteria, T cells are activated and begin producing OPGL and probably allow T cells to activate the development of other blood cells required to fight off infection, Penninger said. Unfortunately, in chronic viral infections, autoimmune diseases and some cancers, T cells do not stop their attack, causing the OPGL-producing T cells to seek out and destroy the body's own bone and cartilage.