Found! How Gene Contributes to Paget’s Disease

Researchers at the Universities of Edinburgh and Dundee in Scotland have identified (for the first time ever) the mechanism by which a certain gene contributes to the development of Paget’s disease. The researchers, led by Omar Albagha, M.Sc., Ph.D., at the Centre for Genomic and Experimental Medicine, have found that a glitch in the gene can trigger the bone defects that affect people with this condition.

As indicated in the October 29, 2015 news release, “The gene—OPTN—regulates the activity of specialised cells that keep bones healthy by breaking down old bone and replacing it. In Paget’s disease the number and activity of these bone-removing cells—called osteoclasts—are increased. This leads to the formation of abnormal bone and development of the disease.”

“The researchers have shown that OPTN regulates bone maintenance by slowing down the formation of bone-removing cells to keep the process of bone-removing and bone-building in balance.”

“The study identifies that genetic variations that increase the risk of disease do so by reducing the amount of OPTN produced by cells. This, in turn, leads to an increase in the number of bone-removing cells, prompting the normal repair process to go into overdrive and causing bones to become deformed and enlarged.”

“The researchers found that the gene is frequently less active in people with increased susceptibility to the disease. Further study found that mice with a defective version of the gene are more prone to the disease. Researchers previously found that genetic variations in OPTN increase the risk of developing Paget’s disease, but its role in bone maintenance was unknown until now.”

Dr. Albagha told OTW, “Using genetic studies, we have previously found that genetic variation in OPTN increase the risk of developing Paget’s disease of bone but the role of this gene in bone metabolism was unknown. In the recent study published in Cell Reports we have identified a novel role of optineurin (OPTN) in bone metabolism as a regulator of osteoclast. Further studies will be needed before this finding can be utilized by orthopaedic surgeons but we have found in a recent study that genetic variations at susceptibility genes can predict disease severity and complications.”