Scientists at The Forsyth Institute have discovered that a compound found in scorpion venom significantly inhibits bone loss found in a model of advanced periodontal disease. The compound may also one day be useful in allaying the bone-destroying effects of inflammatory diseases such as osteoarthritis and rheumatoid arthritis, the research suggests.
The compound, kaliotoxin, was effective in animal studies.
"We are very excited because this is the first demonstration that this type of compound (called a potassium channel blocker) may be useful in treating periodontal disease," said Martin Taubman, DDS, PhD, chair of the Forsyth Department of Immunology, in whose laboratory the research was carried out. "We hope that our findings will lead to success in alleviating the bone-ravaging effects of many other diseases."
At least one-fourth of US residents over age 30 have periodontal disease involving loss of bone or teeth, according to the National Institute for Dental and Cranial Research. Some 21 million individuals in the US are affected by osteoarthritis and nearly 2.1 million have rheumatoid arthritis, according to a 1998 study provided by the Arthritis Foundation.
The Forsyth scientists report in the January 2004 Journal of Bone and Mineral Research that they induced the bone loss component of periodontal disease in rats and injected one group with kaliotoxin. After ten days, animals injected with kaliotoxin exhibited 84 per cent less alveolar (jaw) bone loss than did those that did not receive injections.
According to Paloma Valverde, Ph.D., the principal investigator, kaliotoxin modulates inflammatory bone resorption by blocking the protein Kv1.3, a potassium channel known to be involved in inflammation. "Kaliotoxin decreases the expression of RANKL, a protein expressed on the surface of memory/activated T cells, which are present at high levels in periodontal disease," she said. RANKL plays a key role in inducing bone cells called "osteoclasts" to destroy bone. Thus, kaliotoxin or other potassium channel blockers that target Kv1.3 may reduce bone resorption.
"This is the first known study to show that a potassium channel blocker can decrease alveolar bone loss," Valverde said. "Furthermore, we observed no toxic effects. Therefore we now have a novel and apparently safe strategy to ameliorate bone destruction associated with periodontal disease. We expect that kaliotoxin and other Kv1.3 blockers can also be used to prevent bone destruction in other inflammatory bone resorptive disorders such as osteo- and rheumatoid -arthritis."
Other components of scorpion venom are being studied elsewhere for possible uses in treating autoimmune diseases such as multiple sclerosis and lupus; stroke and heart disease; and certain cancers.
The study, "Kaliotoxin Decreases Alveolar Bone Resorption," was conducted at The Forsyth Institute by Valverde, Toshihisa Kawai, DDS, PhD, and Taubman. Valverde conducted her research as a Staff Associate at Forsyth and Instructor in Oral Biology at the Harvard Dental School. She is now a Scientist II at the USDA Human Nutrition Research Center on Aging at Tufts University. Dr. Kawai is an Assistant Member of the Staff at Forsyth and an Instructor in the Department of Oral and Developmental Biology at the Harvard School of Dental Medicine.
The study was funded by the J.W. Hein Fellowship at The Forsyth Institute and by the National Institute of Dental and Craniofacial Research.
The Forsyth Institute is an independent, nonprofit research organization focused on oral, cranial and related biomedical science.
