Research Matters:
UA Steele Children’s
Investigator Discovers Link between
Protein and Bone Disease
From: Darci Slaten (520)
626-7217
April 21, 2006
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
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.
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