MetS-associated primary OA demonstrated a significant downregulation of anabolic and cell cycle progression, DNA replication, and DNA repair pathways, including decreased G0 and early G1 Reactome, G1/S transcription, prometaphase chromosomal condensation, DNA unwinding, as well as the transcription of E2F targets under negative control by the DREAM complex pathway, indicating a significant reduction in anabolic processes in subchondral bone biopsies. Here, KCNIP3 is linked to metabolic syndrome.