Mount Sinai Researchers Find OA Regulating Gene

Researchers from the Icahn School of Medicine at Mount Sinai in New York have identified a potential new therapeutic target for patients with rheumatoid arthritis (RA).

Their research, “Huntingtin-interacting protein 1 (HIP1) regulates arthritis severity and synovial fibroblast invasiveness by altering PDGFR and Rac1 signaling,” was published on July 26, 2018 in the Annals of the Rheumatic Diseases.

Percio S. Gulko, M.D., chief of the division of rheumatology, the Lillian and Henry M. Stratton Professor of Medicine (Rheumatology) and senior author on the paper told OTW: “There have been major advances in the treatment of rheumatoid arthritis in the past 20 years, but disease remission still remains common.”

“Most drugs today target inflammation but often that is not enough to control disease. At my laboratory, we have been looking for alternative strategies. In this research, we have focused on understanding the regulation of disease severity and joint damage. Our discovery led us to the synovial fibroblasts, cells inside the joint.”

The authors wrote, “An unbiased and phenotype-driven strategy including studies of unique congenic rat strains was used to identify new arthritis severity and joint damage genes. Fibroblast-like synoviocytes (FLS) from rats and patients with RA expressing or not Huntingtin-interacting protein 1 (HIP1) were studied for invasiveness, morphology and cell signaling. HIP1 knockout mice were used in in vivo confirmatory studies…”

“Removing HIP1 significantly reduced the ability of the rheumatoid arthritis synovial fibroblasts to respond to PDGF (platelet-derived growth factor), a potent inducer of synovial fibroblast invasiveness expressed in increased levels in the joints of patients with rheumatoid arthritis.”

“Knockdown of HIP1 prevented the activation of the signaling molecule Rac1, which is key for synovial fibroblast invasiveness. Dr. Gulko and his colleagues also studied HIP1-deficient mice. These mice were protected and developed a milder form of the arthritis.”

Dr. Gulko commented to OTW, “Disease severity and joint damage are major predictors of outcome/prognosis in RA and therefore understanding their regulation is anticipated to generate new and perhaps better targets for treatment.”