UA Steele Children's Research Center Investigator Discovers Link between Protein and Bone Disease

Jennifer Uno, a PhD candidate and researcher with the Steele Children's Research Center working on a study led by Fayez K. Ghishan, MD, professor, has made a discovery that advances the understanding of the relationship between IBD and decreased bone-mineral density (osteopenia). "It's pretty interesting, most people don't think of a connection between their bones and their gut, but the two are inextricably linked," says Ms. Uno.

Every year, more than 30,000 children are diagnosed with Inflammatory Bowel Disease (IBD), a painful gastrointestinal disorder. IBD is a chronic inflammation of the intestinal tract that causes fatigue, diarrhea, stomach pain and weight loss. The two most common forms of IBD are Crohn's disease and ulcerative colitis, and they usually strike children and young adults between the ages of 10-19.
Children and adults suffering from IBD also have an increased risk for bone disease, like osteoporosis. And for growing children with IBD, healthy bones are critical to their growth. Although reduced bone mass is a known complication of IBD, the reasons for this are not completely understood.

But a new finding at the Steele Center sheds light on this mystery.

Jennifer Uno, a PhD candidate and researcher with the Steele Children's Research Center working on a study led by Fayez K. Ghishan, MD, professor, has made a discovery that advances the understanding of the relationship between IBD and decreased bone-mineral density (osteopenia). "It's pretty interesting, most people don't think of a connection between their bones and their gut, but the two are inextricably linked," says Ms. Uno.

What is the connection between IBD and bone-density problems? "Individuals with IBD have uncontrolled pro-inflammatory cytokines," she explains. Cytokines are proteins involved in the inflammatory response and they are also involved with the balance between bone-building and bone-destroying cells, known as osteoblasts and osteoclasts.

"Phosphate is one of the main components of your bones, along with calcium," says Ms. Uno. "Both are needed to develop strong and healthy bones. One of the genes that regulates phosphate is named 'PHEX'" she explains. "So, we wanted to determine if PHEX was impacted by cytokines."

Ms. Uno and her colleagues found that the cytokine "TNF-alpha" down regulates the PHEX gene. "This is like turning the light down with a dimmer," Ms. Uno said. "TNF-alpha turns down the efficacy of PHEX, so phosphate can't do its job to strengthen bones, and consequently bones lose density."

"We have discovered an important piece of the puzzle. This is the first step in a very long process to eventually develop novel therapies to combat bone disease associated with IBD," says Ms. Uno.

The study, "The Role of TNF-alpha in Down-Regulation of Osteoblast PHEX Gene Expression in Experimental Murine Colitis," was recently accepted for publication by the The Journal of Gastroenterology.