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Blood vessels found to signal chain of destruction in bone diseases

Biologists at Washington University in St. Louis have discovered a mechanism in blood vessels that opens the door for bone loss in such diseases as rheumatoid arthritis, periodontal disease, osteoporosis, tumor-associated bone loss, or artificial implant loosening.

Patricia Collin-Osdoby, Ph.D., research associate professor of biology in Arts & Sciences at Washington University, and Philip Osdoby, Ph.D., professor of biology in Arts & Sciences, and Linda Rothe, Washington University research associate, have for the first time shown that blood vessels at inflamed sites where bone loss is occurring create signals that set into motion a cascade of events leading to local bone destruction.

When an area of tissue in or near bone becomes inflamed, key molecules called cytokines are locally produced and increase in the bloodstream. Studying human tissue and cell samples, the Osdobys have shown that two key inflammatory cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), signal the endothelial cells of blood vessels and capillaries to make and display on their cell surface a molecule called RANKL. RANKL is the critical signal that tells the body to make and activate bone-degrading cells called osteoclasts. After osteoclasts take bone away, osteoblasts go back in and add new bone. Normally, this bone remodeling, which is associated with a blood vessel or capillary at such sites, is a carefully balanced process. However, in persons with inflammatory bone disease, osteoclasts out-number and out-work the bone-forming osteoblasts, leading to weakened bone matrix, bone loss, and an increased risk of fracture. The Osdobys believe that inflamed blood vessels beckon cells to the region, and then initiate their development into highly active bone-degrading osteoclasts.

The researchers also found that in this biochemical chain of events, the blood vessels themselves make an antagonist molecule, osteoprotegerin (OPG), whic
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Contact: Tony Fitzpatrick
tony_fitzpatrick@aismail.wustl.edu
314-935-5272
Washington University in St. Louis
26-Jun-2001


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