The key bone-building gene is called the COX-2 gene, shorthand for cyclooxygenase-2, an enzyme that plays a vital role in cartilage and bone repair. COX-2 declines dramatically with age.
“The skeleton loses the ability to repair itself as we age,” said Regis J. O’Keefe, chairman of the Department of Orthopaedics at the University of Rochester Medical Center and corresponding author of the article. “Our results position the COX-2 pathway as one of several under exploration with the common goal of accelerating healing in aging humans, and with the potential to come together in future combination therapies.”
In the O’Keefe study, the bone-healing rates of two groups of mice – one young (seven-nine weeks of age) and one old (52-56 weeks of age) – were compared using imaging and gene-expression techniques. The expression of the COX-2 gene was far less in older mice than in young, and corresponded exactly with the onset of the key healing period.
Most important, the researchers were able to reverse the loss of bone-healing ability in aging mice by using an experimental Pfizer drug that boosts the effect of COX-2. The drug fills a missing link that develops in the COX-2 cell-stimulation pathway in aged mice. As COX-2 levels diminish with age, the chain reaction that’s required to stimulate bone marrow stem cells, cartilage cells and bone-producing cells (osteoblasts) weakens to a trickle.
The experimental drug, CP-734432, apparently mimicked one element in the COX-2 pathway, boosting fracture repair in the older mice with more efficient formation of mature bone. The drug was also recently used to prevent osteoporosis in early animal studies.