A team of researchers from Hospital for Special Surgery (HSS) has identified a new cell signaling pathway that contributes to the development and progression of inflammatory bone erosion, which occurs in patients with rheumatoid arthritis (RA).
HSS: New Cell Signaling Pathway Important in RA
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The study, published online in the Journal of Clinical Investigation on October 20, 2014, was led by Baohong Zhao, Ph.D. Dr. Zhao is assistant scientist in the Arthritis and Tissue Degeneration Program at HSS. The October 20, 2014 news release notes, “Recently, other scientists conducted a genome-wide association study to identify genes linked to RA development. They discovered that a certain variant in a gene called RBP-J [recombination signal binding protein for immunoglobulin] was associated with the development of RA, but its specific role was unknown.”
“We found for the first time that the expression level of this risk gene in RA patients is significantly lower than the level in healthy controls, thus providing important evidence of the link between this risk gene and RA disease, ” explained Dr. Zhao in the October 20, 2014 news release.
Dr. Zhao told OTW, “As the RBP-J-controlled signaling pathway (identified in our paper) regulates osteoclast differentiation, which is a major component of bone remodeling, our study has implications in physiological and pathological bone remodeling, such as those that occur in the healing of bone fractures and peri-prosthetic loosening.”
“We are very excited about our results, because this newly identified RBP-J-controlled signaling pathway will provide potential novel therapeutic targets for the prevention and treatment of RA, thus opening a new avenue for both basic research and clinical care, ” said Dr. Zhao in the news release.
The scientists were fortunate to have access to a high-tech next generation technology known as whole transcriptome sequencing. With this tool, the researchers were able to obtain information on the expression level of each single gene among thousands of human genes. The new technology and analysis were supported by the David Z. Rosensweig Genomics Research Center at HSS, which is supported by The Tow Foundation and led by Lionel B. Ivashkiv, M.D., associate chief scientific officer at HSS. Dr. Zhao is also a member of this center. The study was supported by research grants from the National Institutes of Health (NIH).
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This is a fascinating development. In my practice we've seen similar outcomes with the revised protocol. The key differentiator seems to be patient selection criteria. Has anyone else noticed the correlation with BMI thresholds?
Great point. I'd push back slightly on the conclusion, the sample size in the cited study is too small to draw population-level inferences. That said, the directional signal is compelling and worth a larger RCT.
We implemented a similar approach last year. Early results are promising but we're still gathering 12-month follow-up data. Happy to share our protocol if anyone is interested.
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