Protein Protects Against Arthritis-Related Bone Loss

Researchers from Georgia Regents University (GRU) have found that a small protein named GILZ may be protective against bone loss that can accompany arthritis and the medicine meant to treat it. Could the drugs currently in use—which have the side effects of bone loss and diabetes—be supplanted by GILZ?

Working with colleagues, Dr. Xing-Ming Shi, Ph.D., a bone biologist at the Medical College of Georgia (MCG) at GRU, focused on “tumor necrosis factor alpha, a proinflammatory cytokine that helps regulate immune cells and is a major player in arthritis. Tumor necrosis factor alpha primarily works though promoting inflammation, which is great if the target is cancer. However, when tumor necrosis factor alpha becomes dysregulated, it can also cause diseases like arthritis and inflammatory bowel disease.”

Per the September 12 MCG press release: “The researchers crossed mice bred to overexpress tumor necrosis factor alpha throughout the body with mice that overexpressed GILZ in just their mesenchymal stem cells. These stem cells produce the osteoblasts, which make bone. They also make fat, and when the cells stop making as much bone, they tend to make more of it. Shi’s lab has shown that GILZ can coax mesenchymal stem cells back to making more bone and less fat.”

Dr. Shi said, “While the mice that overexpressed only tumor necrosis factor alpha quickly developed arthritis along with significant bone and weight loss, those that also overexpressed GILZ had significantly less bone loss.”

“Our previous studies have shown that the GILZ transgenic mouse can make more bone, ” said Dr. Nianlan Yang, MCG postdoctoral fellow. “We wanted to see if GILZ would still have a bone protective effect in an inflammatory environment similar to arthritis.”

As indicated in the news release, “Glucocorticoids and GILZ are both produced naturally in the body. Glucocorticoids are steroid hormones that help regulate the body’s use of the fuel glucose and dampen the immune response.”