Epigenomic differences between osteoarthritis grades in primary cartilage

Objective: Osteoarthritis is a common and complex joint disorder that shows higher prevalence and greater disease severity in women. Here, we investigate genome-wide methylation profiles of primary chondrocytes from osteoarthritis patients. Design: We compare genome-wide methylation profiles of macroscopically intact (low-grade) and degraded (high-grade) osteoarthritis cartilage samples matched from osteoarthritis patients undergoing knee replacement surgery. We perform an epigenome-wide association study for cartilage degeneration across 170 patients and separately in 96 women and 74 men. Results: We reveal widespread epigenetic differences with enrichments of nervous system and apoptosisrelated processes. We further identify substantial similarities between sexes, but also sex-specific markers and pathways. Conclusions: Together, we provide the largest genome-wide methylation profiles of primary cartilage to date with enhanced and sex-specific insights into epigenetic processes underlying osteoarthritis progression. (c) 2024 The Authors. Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).