Biochemical tests revealed that HDAC4 controls the early timing of osteogenesis by preventing the final step, bone hardening from occurring. By specifically blocking a protein called Runx2, which controls the genes for bone hardening, HDAC4 allows the foundation and minerals to be properly laid before hardening can occur.
Dr. Olson said he believes that calcium, which is required for healthy bones, may signal the release of HDAC4 from Runx2 to initiate the bone-hardening program.
"The discovery that bone formation is controlled by HDAC4, an enzyme, raises possibilities for designing drugs to control this process in the settings of bone diseases, such as osteoporosis," he said. "In fact, HDAC inhibitors are currently being used for the treatment of certain cancers. It will be interesting to investigate whether these inhibitors influence the process of bone formation."
Other UT Southwestern contributors to this study include Dr. Rick Vega, former postdoctoral researcher and lead author; Dr. James Richardson, professor of pathology and molecular biology; Dr. John Shelton, research scientist in internal medicine; Dr. Ana Barbosa, postdoctoral researcher in molecular biology; Dr. Junyoung Oh, former postdoctoral researcher in molecular biology; Eric Meadows and John McAnally, research technicians in molecular biology; Chris Pomajzl, former senior histology technician in pathology; and collaborators at Baylor College of Medicine.
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Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
11-Nov-2004