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Researchers detail how aging undermines bone healing
Date:1/15/2009

expressed primarily in early stem cell precursors of cartilage that also express collagen, type II, alpha 1 (col2a1), the gene that codes for production of a key part of type II collagen in mice and humans, the fibrous, structural protein that lends strength to bone. Researchers observed in aged mice a dramatic decrease as well in the expression of other genes known to contribute to bone formation as well (e.g. osteocalcin and type X collagen). Altogether the results suggest that in aging animals gene expression is altered early in fracture repair with consequences for the entire healing cascade.

Researchers found further proof that COX-2 is responsible for loss of bone healing ability with age when they were able to reverse the process with a drug known to encourage the COX-2 signaling effect. COX-2 catalyzes the conversion of a fatty acid to prostaglandin E2 (PGE2), a hormone with many functions in the animal body depending on the type of cell they interact with, from blood vessel dilation to embryo implantation in the womb to bone healing. PGE2 is known to have it effect on cells by reacting with one of four receptor proteins (EP1EP4) on the surface of cells, including the surfaces of bone marrow stem cells, cartilage cells and bone-producing cells (osteoblasts). Human cells send and receive signals that switch on life processes through workhorse proteins called receptors that enable messages to penetrate cells.

Prior work in other labs had established that the ability of PGE2 to create new bone growth occurs in particular through its interaction with the EP4 receptor. In the current study, the team showed that delayed fracture healing observed in aged mice could be rescued with local delivery of an experimental drug, CP-734432, which directly activates the EP4 receptor in place of the missing COX-2 (an EP4 agonist). The drug, provided to the team by Pfizer Inc., was also recently used to prevent osteoporosis in early animal studies. Local inje
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Contact: Greg Williams
Greg_Williams@urmc.rochester.edu
585-267-7557
University of Rochester Medical Center
Source:Eurekalert

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