Controlling inflammation ‘exceptionally well’ can heal rheumatoid arthritis bone erosions
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Strictly controlling inflammation can heal bone erosions in rheumatoid arthritis, a process accompanied by changes in the Wnt signaling pathway, according to a presenter at the 2024 Association of Women in Rheumatology conference.
“Repair occurs in about 10% of cases, and it occurs in states of low disease activity post-therapy,” Ellen M. Gravallese, MD, chief of the division of rheumatology, inflammation and immunity at Brigham and Women’s Hospital, in Boston, told attendees. “If you’re really effective at getting inflammation under control, those osteoblasts can come in and repair the bone. In fact, in specific joints, we can demonstrate that the joints where there’s healing of bone are the joints where inflammation has been well-controlled.”
To understand more about that process, Gravallese worked with researcher Melissa Matzelle, PhD, on a mouse study, which was published in 2012.
While generating arthritis in mice using serum transfer, Matzelle observed that if the serum was stopped, inflammation peaked and decreased, according to Gravallese. A method “similar to tetracycline labeling” was devised to measure bone formation at the erosion site, she added.
“What we found is that at day 10, at peak inflammation, there’s no bone being made, essentially, but by day 28, when the inflammation is waning, there’s a huge increase in bone formation rates,” Gravallese said. “By day 58, we couldn't find any erosions in these mice, suggesting that all of these had healed.”
The researchers found that during early, uncontrolled inflammation, there were “very few, if any” osteoblasts at the erosion sites, she added. However, by day 21, osteoblasts were lining the sites and forming bone, according to Gravallese.
“What we learned from this is that you really need to control inflammation exceptionally well in order to get healing of erosions,” she said.
Another key finding was made in synovial tissues of the mice. Along with pro-inflammatory cytokines, inhibitors of the Wnt signaling pathway were being produced, especially by fibroblasts in the synovial tissue.
“As inflammation wanes, the production of cytokines and Wnt signaling inhibitors disappears,” Gravallese said. “In fact, we were able to show that, as inflammation completely wanes, we start to see ligands of the Wnt pathway leading to erosion repair. So, resolution of inflammation suppresses Wnt antagonists being produced, and resolving inflammation promotes erosion repair.”
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Gravallese EM. Latest Advances and Therapeutic Approaches in RA. Presented at: Association of Women in Rheumatology annual conference; July 25-27, 2024; Orlando, Florida (hybrid meeting).
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