Dr. Eric Olson, chairman of molecular biology, and colleagues have shown the protein HDAC4 to be essential for proper bone development, or osteogenesis. Their findings, reported in the November issue of the journal Cell and available online, may have widespread implications for understanding and preventing osteoporosis or other bone disorders, said Dr. Olson, senior author of the study.
"This was a very unexpected discovery. We were studying the role of the HDAC4 gene in the control of heart growth. When we created genetically modified mice lacking the HDAC4 gene, we found that they had excess bone and died because their cartilage was converted into bone," said Dr. Olson, who directs the Nancy B. and Jake L. Hamon Center for Basic Research in Cancer and the Nearburg Family Center for Basic Research in Pediatric Oncology.
The process of bone formation occurs in three stages, orchestrated by specialized bone cells that secrete and absorb materials as needed. First, a soft cartilage-based foundation is laid, upon which mature bone will solidify. Then, minerals containing calcium and phosphate are deposited throughout the foundation, creating a framework for the bone. Finally, this raw material is sculpted and hardened into bone. Missteps in this process can result in developmental defects and bone diseases.
HDAC4 belongs to a family of enzymes that inactivate genes. Unlike other members of this family which are found in numerous tissues, HDAC4 is expressed in only a few tissues, including bone.
Dr. Olson and colleagues studied mice lacking the HDAC4 gene. At birth these animals had misshapen skulls and spines, and as they got older, failed to thrive.