The study appears in the first March issue of the Journal of Clinical Investigation and is published online March 4.
"Because of our previous research with these proteins, new drugs already are in clinical trials," says lead investigator Steven L. Teitelbaum, M.D., the Wilma and Roswell Messing Professor of Pathology and Immunology. "But we still do not understand how these proteins interact to affect bone-cell development. This study brings us significantly closer to determining that mechanism."
Osteoporosis, a condition that results in weakened, brittle bones, afflicts roughly 50 percent of Caucasian and Asian women after age 65. It develops when bone is broken down at a faster rate than it is synthesized. Therefore, curing the disease and others like it depends on understanding osteoclasts -- cells responsible for eroding bone -- and determining why they sometimes become overly active.
Teitelbaum's team previously determined that M-CSF helps unspecialized bone cells develop into mature osteoclasts. Without enough M-CSF to encourage osteoclast growth, animals develop abnormally dense bone. Similarly, it is known that blocking alphaV beta3 integrin in animal models causes failure of osteoclast function. However, it is unclear precisely how M-CSF or alphaV beta3 integrin influence osteoclast development.
The absence of beta 3 (part of the alphaV beta3 integrin) in precursor cells has a curiously different effect on cells in a petri dish compared with cells in living animals. When grown in a dish, abnormally few osteoclasts develop, and those that do develop are dysfunctional. In animals, however, precurso
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Contact: Gila Z. Reckess
reckessg@msnotes.wustl.edu
314-286-0109
Washington University School of Medicine
4-Mar-2003