Protein could be key for drugs that promote bone growth

Georgia Health Sciences University researchers have developed a mouse that errs on the side of making bone rather than fat, which could eventually lead to better drugs to treat inflammatory diseases such as rheumatoid arthritis. Dr. Xingming Shi, bone biologist at the GHSU Institute of Molecular Medicine and Genetics and Graduate Student Guodong Pan say the key to the body developing bone instead of fat is a small protein called GILZ. Credit: Phil Jones

Georgia Health Sciences University researchers have developed a mouse that errs on the side of making bone rather than fat, which could eventually lead to better drugs to treat inflammatory diseases such as rheumatoid arthritis.

Drugs commonly used to treat those types of conditions – called glucocorticoids – work by turning down the body's anti-inflammatory response, but simultaneously turn on other pathways that lead to bone loss. The result can lead to osteoporosis and an accumulation of marrow fat, says Dr. Xingming Shi, bone biologist at the GHSU Institute of and Genetics.

The key to the body developing bone instead of fat, a small protein called GILZ, was shown in in 2008. Now, with work by GHSU Graduate Student Guodong Pan, the work has been replicated in an animal model. Pan received the American Society for Bone and Mineral Research's Young Investigator Award for his work at the society's annual meeting Oct. 12-15 in Minneapolis.

Bone and marrow fat come from the same biological precursor – mesynchymal . "The pathways for bone and fat have a reciprocal relationship, so we needed to find the key that disrupts the fat production pathway, which would then instead encourage bone growth," Shi says.

GILZ, Shi and Pan say, was already a known mediator of the anti- of glucocorticoids, and the protein also mediates bone production. Shi's early research had shown that glucocorticoids enhance in the lab because of a short "burst" of GILZ.

The protein works by inhibiting the way cells regulate fat production and turn on fat-producing genes, Shi says. "When you permanently express GILZ, the fat pathway is suppressed, so the body chooses to produce bone instead."

"We found that when we overexpressed the protein in these mice, it increased bone formation," Pan added. "This supports our original hypothesis that GILZ mediates the body's response to glucocorticoids and encourages bone growth." In fact, the genetically modified mice showed a significant increase in bone mineral density and bone volume as well, he found.

"That means GILZ is a potential new anti-inflammatory drug candidate that could spare people from the harmful effects associated with glucocorticoid therapy," Pan said

Long-term goals, Shi said, are developing the GILZ-like pill that is anti-inflammatory and protects or even increases bone production.

add to favorites email to friend print save as pdf

Related Stories

Growth hormone increases bone formation in obese women

Nov 29, 2011

In a new study presented today at the annual meeting of the Radiological Society of North America (RSNA), growth hormone replacement for six months was found to increase bone formation in abdominally obese women.

Recipient's immune system governs stem cell regeneration

Nov 20, 2011

A new study in Nature Medicine describes how different types of immune system T-cells alternately discourage and encourage stem cells to regrow bone and tissue, bringing into sharp focus the importance of the transplant recipient's ...

Recommended for you

Mystery of the reverse-wired eyeball solved

23 hours ago

From a practical standpoint, the wiring of the human eye - a product of our evolutionary baggage - doesn't make a lot of sense. In vertebrates, photoreceptors are located behind the neurons in the back of the eye - resulting ...

Neurons controlling appetite made from skin cells

23 hours ago

Researchers have for the first time successfully converted adult human skin cells into neurons of the type that regulate appetite, providing a patient-specific model for studying the neurophysiology of weight ...

Quality control for adult stem cell treatment

Feb 27, 2015

A team of European researchers has devised a strategy to ensure that adult epidermal stem cells are safe before they are used as treatments for patients. The approach involves a clonal strategy where stem cells are collected ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.