RA-risk synovium exhibits DNA damage coupled with impaired DNA repair in fibroblasts.

ABSTRACT:

Objectives

Understanding the molecular changes in the preclinical synovium is crucial for identifying factors that drive arthritis development. Persistent DNA damage in tissues is known to drive a senescent microenvironment, genomic instability and ultimately chronic inflammation. Here, we determined cellular DNA damage and repair capacity within synovial tissue from rheumatoid arthritis (RA) patients and individuals at risk of developing RA.

Methods

We investigated the presence of senescence-associated DNA damage in synovial biopsies and synovial fibroblasts obtained during different phases of RA. Histone 2A is phosphorylated (γH2AX) at the site of a double-stranded DNA break where DNA repair proteins are recruited and is therefore a proxy measurement for DNA damage. In thi

SUBMITTER: O'Byrne AM 

PROVIDER: S-EPMC12829405 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature