Abstract
Human osteoarthritis (OA) displays sex-specific patterns in its clinical presentation. Key features of the disease-such as prevalence, age of onset, progression, and response to treatment-vary between males and females. These differences have been associated with sex hormones, as well as anatomical, biomechanical, and behavioral distinctions between the sexes. However, the underlying mechanisms driving these sex-specific disparities in OA pathogenesis remain largely unknown. In this study, we analyzed transcriptomic data from human knee articular cartilage to investigate sex-specific gene expression in articular chondrocytes. We identified genes that are uniquely or predominantly expressed in either males or females in healthy cartilage. Notably, many of these sex-biased genes were significantly dysregulated in osteoarthritic cartilage, particularly those with higher expression in females. Furthermore, female-specific OA genes may exert protective effects on cartilage degeneration, whereas male-specific OA genes could impair cartilage homeostasis. Our findings provide insights into the genetic regulation of OA and highlight the influence of sex on its molecular pathology.