Researchers used single-cell RNA sequencing and spatial transcriptomics to map cellular senescence in osteoarthritic joint tissues from humans and mice. They discovered that EGFR⁺ mesenchyme-derived stem/progenitor cells (MDSPCs) in subchondral bone become senescent during OA, driven by the signaling molecule EREG secreted by neighboring EREG⁺ macrophages. This paracrine interaction forms a 'senescent skeletal unit' that promotes excessive bone hardening and pain. Blocking EREG — via AAV-mediated knockdown or genetic knockout in mice — reduced stem cell senescence, subchondral bone sclerosis, and OA-related pain. The findings position EREG and EGFR⁺ MDSPCs as promising therapeutic targets for osteoarthritis.
