Scientists conducting laboratory experiments on mice have discovered that their fat cells secrete a protein linked to arthritis, a finding that could pave the way for new gene therapies to treat rheumatoid arthritis.
“We found that fat in the knee joints secretes a protein called pro-factor D which gives rise to another protein known as factor D that is linked to arthritis,” said Nirmal Banda, PhD, associate professor of medicine in the Division of Rheumatology at the University of Colorado School of Medicine. “Without factor D, mice cannot get rheumatoid arthritis.”
Rheumatoid arthritis is an autoimmune disease that gradually destroys joints, cartilage and other connective tissue. Over 1% or about 1.3 million Americans suffer from it.
Banda, senior author of a study published in the Journal of Immunology, has spent the last 14 years tracking down the causes of rheumatoid arthritis in collaboration with other researchers at the CU School of Medicine.
Now, with the discovery of pro-factor D in mice with rheumatoid arthritis, he is working on gene therapies to eliminate the protein. His theories still need to be tested on humans.
“We are looking at vaccines, drugs or inhibitors to stop the local secretion of pro-factor D in the mouse,” he said. “Our goal would be to stop the disease before it progresses and leads to joint destruction.”
Factor D is part of a complex array of over 40 proteins known as the complement system that help the body fight off bacteria and other infections. In previous studies with arthritic mice, Banda found that factor D made the mice susceptible to inflammatory arthritis.
“We know that fat is normally present around all organs of the body,” he said. “But what we didn’t know until now was that the fat is secreting this protein which actually triggers arthritis in the joints.”
He noted that fat does the same thing in all the joints, not just the knees. That means new medications resulting from this discovery could treat inflammatory arthritis throughout the body.
“The complement system is both friend and foe,” Banda said. “We believe we can shut down one part of the complement system that triggers disease without shutting down the rest. If so, we will be making a major stride toward treating and perhaps even curing rheumatoid arthritis.”