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Small protein may have big role in making more bone and less fat
Date:7/1/2008

t turn on this fat-producing gene. One way GILZ does this is by binding to the regulatory region of PPAR2, Dr. Shi has shown.

To restore a healthier balance of bone and fat production, sustained GILZ action is needed. "When you permanently express GILZ, cells cannot differentiate into fat cells. Instead, you increase bone formation. People like this idea," says Dr. Shi, who has watched the mesynchymal stem cell production shift.

One point of controversy is that, at least in the lab, glucocorticoids seem to enhance bone formation. But Dr. Shi believes it's the short burst of GILZ at work there. He wants to know exactly how it works to see if it could offer a targeted therapy for osteoporosis and obesity and maybe a safer option for many who need glucocorticoids.

A recent $1.5 million, five-year grant from the National Institute of Diabetes and Digestive and Kidney Diseases is enabling Dr. Shi to further test his hypothesis about how GILZ represses PPAR2 and to see if GILZ over-expression in mice reduces PPAR2 expression and consequently increases bone and decreases fat. A long-term goal is to understand exactly how PPAR2 controls fat and bone production.

GILZ also is a powerful immune and inflammation suppressor. It inhibits two key inflammatory molecules, NF-kB and AP-1, which turn on inflammatory genes in response to cytokines, such as TNF- and IL-1, involved in rheumatoid arthritis and other inflammatory diseases, Dr. Shi showed in research published on the cover of the April 15 issue of Journal of Cellular Biochemistry. That study notes GILZ's potential as a novel anti-inflammatory therapy.

In fact, Dr. Shi believes GILZ is a key factor mediating the anti-inflammatory effects of glucocorticoids. A long-acting version of GILZ or a similar substance would be needed to produce, for example, a powerful new arthritis treatment minus the undesirable effects. About 50 percent of arthritis patients who take glucoco
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Contact: Toni Baker
tbaker@mcg.edu
706-721-4421
Medical College of Georgia
Source:Eurekalert  

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