Dr. Gravallese says there may be other factors that keep the bone from healing. For instance, the chronic nature of RA may cause a permanent change in the marrow environment, or may prevent osteoblasts from getting into the site.
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To study the process of osteoblast differentiation, Dr. Gravallese’s team also looked at synovial tissues in the serum transfer model for factors that might be regulating bone formation. They found that when inflammation is at its peak, there is expression of inhibitors of the Wnt signaling pathway (the network of proteins involved in the differentiation and positive function of osteoblasts). As the inflammation decreases, expression of the inhibiting factors also begins to decrease. “Inflammation seems to be regulating expression of factors that affect Wnt signaling,” says Dr. Gravallese.
This research may have far-reaching implications, because treatments that are able to more effectively control inflammation could help trigger bone formation in patients with RA. Dr. Gravallese presented her findings in January at the Keystone Symposia Meeting on Rheumatoid Arthritis, which was organized with the support of the REF.
She credits the Within Our Reach: Finding a Cure for Rheumatoid Arthritis grant she received from the REF as a key factor in the research process. “The grant allowed us to go in a completely new direction, focusing on osteoblasts and the process of bone formation. It also allowed us to generate quite a bit of preliminary data,” says Dr. Gravallese, “and we were able to obtain new funding based on these data.”