Distinct subsets of synovial fibroblasts in rheumatoid arthritis development identified.
Researchers recently identified different roles that synovial fibroblasts (SFs) play in the development of rheumatoid arthritis (RA), providing new information for future treatment options.
SFs comprise the synovium around human joints, but in patients with RA, the SF cells wreak havoc on the body by invading and attacking the cartilage and bone around the joint.
In a new study published in Arthritis Research & Therapy, researchers identified 2 distinct types of SF within the synovial membrane.
The cell types are defined by the presence of specific cell surface markers called PDPN and CD248, and they aggregate in different layers of the synovium. The results of the study found that only the PDPN type is responsible for cartilage damage in RA patients.
For the study, SF cells obtained from RA patients were grown in vitro within an artificial synovium and were activated using cytokines. The artificial synovium was then inserted into a mouse, whose immune system was turned off, as well as a human cartilage to simulate a joint.
The researchers wanted to examine how the SF cells would develop in vivo. After implantation, tests showed that the lining layer of the artificial synovium contained invasive PDPN type SFs, while the part that was further away from the cartilage contained the non-invasive CD248 type.
Recent findings have shown that activated SF cells can migrate, which the current study confirmed. In the new study, researchers built upon these findings by demonstrating that PDPN type SF cells were the first to migrate, while the CD248 cells only appeared at a later stage in secondary tissue.
“This study not only shows the existence of distinct subsets of synovial fibroblasts, but also suggests that these cells are able to self-organize into lining and sub-lining layers in the presence of cartilage,” said lead researcher Dr Adam Croft. “Combined with the difference in migration rates between the 2 types of cell, these results are extremely promising in terms of finding new therapeutic targets for treatment of rheumatoid arthritis.”
The findings suggest that by targeting SF cells processes it could make future treatments more effective and manageable, the authors noted.