A research team at the University of Massachusetts Medical School in Worcester has made important findings regarding bone erosion and formation that may lead to better treatment options for people impacted by rheumatoid arthritis (RA).
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Explore This IssueJune 2012
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Ellen Gravallese, MD, rheumatology division chief and professor of medicine and cell biology at the University of Massachusetts, received a two-year disease-targeted research grant from the ACR Research and Education Foundation in 2008 to study how osteoclasts and osteoblasts affect bone erosion and healing in RA.
Her lab had previously published studies identifying osteoclasts as cell types involved in bone erosion in patients with RA. In addition, her team had identified receptor activator of NF-κB ligand in synovial tissue as an important factor driving osteoclast differentiation in arthritis. With the clinical use of disease-modifying and biologic agents, rheumatologists observed that the osteoclast-mediated erosive process could be retarded or even arrested. However, there was little evidence of new bone formation. “There was no further erosion, but it’s rare to see bone repair,” says Dr. Gravallese. “In normal bone remodeling, osteoblasts would fill in bone that had been lost or removed.”
With the assistance of the REF grant, Dr. Gravallese’s team decided to focus more closely on osteoblasts. Dr. Gravallese poses the research as a simple question: Once there has been erosion introduced by RA, is it possible to heal the bone?
“What this work suggests is that when we don’t see bone healing in RA, there may still be inflammation present, even though we don’t recognize it clinically.”
—Ellen Gravallese, MD
Her team tested this question by using the serum transfer arthritis model. Mice were injected with arthritogenic serum, leading to inflammation and bone erosion. After the injections were stopped, the inflammation would begin to disappear. But would the bones heal?
“When inflammation was at its peak, very little bone was being laid down,” says Dr. Gravallese. “But as the inflammation resolved, we began to see bone formation at prior inflammation–bone interfaces.”
Peak inflammation occurred around Day 10 after the initial serum transfer. By Day 21, mature osteoblasts began to enter the site of erosion. By Day 28, bone formation was observed, and the bone continued to repair over the next several weeks. “What we found,” says Dr. Gravallese, “is that as inflammation resolves, you see that bone can be formed at that site. What this work suggests is that when we don’t see bone healing in RA, there may still be inflammation present, even though we don’t recognize it clinically.”