NOTCH2 disrupts the synovial fibroblast identity and the inflammatory response of epiphyseal chondrocytes.

ABSTRACT: Notch signaling plays a fundamental role in the inflammatory response and has been linked to the pathogenesis of osteoarthritis in murine models of disease and humans. To address how Notch signaling modifies transcriptomes and cell populations, we examined the effects of NOTCH2 in chondrocytes from mice harboring a NOTCH2 gain-of-function mutation (Notch2^tm1.1Ecan) and a conditional NOTCH2 gain-of-function model expressing the NOTCH2 intracellular domain (NICD2) from the Rosa26 locus (R26-NICD2 mice). Bulk RNA-Sequencing (RNA-Seq) of primary epiphyseal cells from both gain-of-function models established increased expression of pathways associated with the phagosome, genes linked to osteoclast activity in rheumatoid arthritis signaling, and pulmonary fibrosis signaling. Expressio

SUBMITTER: Canalis E 

PROVIDER: S-EPMC12179613 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature