Simulated microgravity models sex differences in knee osteoarthritis through a CD36-regulated mechano-metabolic circuit

Initial results from our investigations reveal that SMG significantly alters the molecular expression profiles in engineered meniscus constructs derived from non-KOA patients, notably influencing genes related to chondrocyte hypertrophy and OA progression while downregulating protective genes. Further analysis has illuminated sex-specific molecular responses to SMG, demonstrating pronounced differences between male and female specimens.

This highlights the importance of considering biological sex in OA research, as it significantly influences disease development and response to microgravity conditions. Extended RNA sequencing under SMG conditions has identified distinct molecular signatures for different sex-based groups, pointing towards an OA-like transcriptome profile in females particularly responsive to SMG. One of the most significant findings from our microgravity studies is the modulation of CD36, a transmembrane protein implicated in lipid metabolism and OA pathogenesis.

Its altered expression under SMG conditions and known upregulation in KOA patients underscore the potential mechanisms by which microgravity-induced cellular responses can mimic and inform us about OA development, particularly in terms of sex-specific disparities.