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Updated: May 13, 2026

An Adoptive Transfer Model of Rheumatoid Arthritis in Mice
Published on: June 6, 2025
BRAF splice variants in rheumatoid arthritis synovial fibroblasts activate MAPK through CRAF
Richard H Weisbart1, Grace Chan, Erica Li
1Veterans Affairs Greater Los Angeles Health Care System, Sepulveda, CA 91343, USA. rweisbar@ucla.edu
Abstract:
Rheumatoid arthritis (RA) is a destructive polyarthritis in which synovial-like fibroblasts (SFs) invade and erode cartilage by expressing membrane-anchored type 1 matrix metalloproteinase (MT1-MMP). The mitogen activated protein kinase (MAPK) pathway is activated in RA SFs, but the mechanism of activation is unknown. Here we identify aberrant BRAF splice variants with deletions in both the kinase domain and RAS-binding domain (RBD) in SFs from the majority of RA patients and show that these BRAF splice variants constitutively activate MAPK through CRAF, increase expression of MT1-MMP, and enhance fibroblast invasion of collagen.
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