Recent findings published in the Journal of Biological Chemistry
Researchers at the University of Missouri-Kansas City (UMKC) School of Dentistry have identified an important new mechanism in the process by which bones build and maintain both strength and elasticity. The results of their most recent findings were published in the January 21 issue of the Journal of Biological Chemistry.
“Bone forms in an unusual way — its cells intentionally entomb themselves in a mineralized protein matrix which they themselves produce,” said Jeff Gorski, Ph.D., professor of Oral Biology at the UMKC School of Dentistry and lead author of the journal publication. “As part of our ongoing research, we discovered that a specific enzyme — subtilisin-kexin-like protease 1 (SKI-1) — is required for bone mineralization.”
By studying bone cells in culture dishes, the researchers were able to show that no bone mineralization takes place if SKI-1 is deactivated. Alternatively, they observed that if the actions of SKI-1 are stimulated, more mineralization takes place, triggering the expression/production of the several proteins that form the bone’s mineralized matrix. Previous work by others found that the absence of just one of those proteins is sufficient to lead to abnormal bone formation.
“Bone is composed of about 65 percent by weight of calcium and phosphorus. It is this mineral content that gives bone its unique structural strength and explains why persons with lower mineral, such as the elderly or those with osteoporosis, have a greater tendency to suffer bone fractures,” Dr. Gorski said. “The protein content of bone comprises another 25 percent of its weight and is responsible for bone’s elastic properties, which allows bones to bend before breaking.”
Dr. Gorski believes that future development of therapeutic ways to measure and control SKI-1 function could have significant therapeutic and diagnostic implications.
“This could lead us toward improvements in preserving bone strength with age, which could have a significant impact in treating osteoporosis as well as other diseases that can lead to lowered bone mineral content, including HIV infection, epilepsy and juvenile diabetes,” he said.
SKI-1 is also known to play a key role in the process of fat cell formation, or adipogenesis. Since fat and bone represent two alternate choices for bone marrow stem cells, scientists may be able to stimulate bone formation after fracture by selectively preventing SKI-1’s adipogenic actions and favoring its osteogenic (bone formation) actions.
“Finally, by virtue of its central metabolic role, measurements of SKI-1 could fulfill a need for biomarkers of bone formation to help clinicians quickly monitor bone health,” he said.
Dr. Gorski and his fellow investigators are part of the Bone Biology Group in the UMKC Center of Excellence in the Study of Dental and Musculoskeletal Tissues (CEMT), a multidisciplinary and interdisciplinary center that includes investigators from the UMKC Schools of Dentistry, Medicine, Nursing, Biological Sciences and Computing and Engineering.
Co-authors of the Journal of Biological Chemistry article include Nichole T. Huffman and Claudine Black, UMKC; Sridar Chittur, University at Albany; Ronald J. Midura, Lerner Institute, Cleveland Clinic; Julie Oxford, Boise State University; and Nabil G. Seidah, Institut de Recherches Cliniques de Montreal. Click here for the article abstract and a link to a PDF of the full article.
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