Hospital for Special Surgery Researchers Identify New Cell Signaling Pathway Thought to Play Role in Rheumatoid Arthritis

Rheumatoid arthritis is a systemic inflammatory autoimmune disease that affects millions of people worldwide. Bone erosion in joints is a major cause of disability in RA patients.

The study, titled "RBP-J imposes a requirement for ITAM-mediated costimulation of osteoclastogenesis," was published online in the Journal of Clinical Investigation on October 20. Baohong Zhao, PhD, lead investigator and assistant scientist in the Arthritis and Tissue Degeneration Program at HSS, and colleagues uncovered a novel signaling pathway and elucidated the underlying mechanisms that could contribute to bone destruction in RA.

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 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.

The scientists also elucidated mechanisms by which the RBP-J protein controlled excessive bone erosion through a newly identified signaling pathway. "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.

The scientists used powerful high-tech next generation whole transcriptome sequencing, which can provide information on the expression level of each single gene among thousands of human genes. "This technology enabled us to unravel key components of this new signaling pathway," said Dr. Zhao.

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, MD, associate chief scientific officer at HSS. Dr. Zhao is also a key member of this center.

The study was supported by research grants from the National Institutes of Health (NIH), including a three-year grant from the NIH/NIAMS Pathways to Independence Award. Other authors involved in the study include Susan Li; Christine Miller (co-first author); Eugenia Giannopoulou, PhD; Xiaoyu Hu, PhD; and Lionel B. Ivashkiv, MD, all from HSS.

About Hospital for Special Surgery

Founded in 1863, Hospital for Special Surgery (HSS) is a world leader in orthopedics, rheumatology and rehabilitation. HSS is nationally ranked No. 1 in orthopedics, No. 3 in rheumatology and No. 7 in geriatrics by U.S.News & World Report (2014-15), and is the first hospital in New York State to receive Magnet Recognition for Excellence in Nursing Service from the American Nurses Credentialing Center three consecutive times. HSS has one of the lowest infection rates in the country. HSS is a member of the New York-Presbyterian Healthcare System and an affiliate of Weill Cornell Medical College and as such all Hospital for Special Surgery medical staff are faculty of Weill Cornell. The hospital's research division is internationally recognized as a leader in the investigation of musculoskeletal and autoimmune diseases. Hospital for Special Surgery is located in New York City and online at http://www.hss.edu.