Microgravity-related transcriptomic changes during in vitro chondrogenesis

Osteoarthritis (OA) remains an incurable joint disease with a high failure rate in clinical trials, largely due to inadequate preclinical models that fail to recapitulate the mechanobiological complexity of human cartilage. This study investigates the utility of simulated microgravity, using a random positioning machine (RPM), as a rapid and mechanistically faithful platform for modeling OA-like changes in chondrogenic cultures. We used RPM-exposed chicken chondrogenic micromass cultures to dissect stage-specific responses to mechanical unloading, from early differentiation (days 0-3) to matrix maturation (days 3-6). We demonstrated that stimulated microgravity disrupts TGFb/BMP balance and induces ECM degradation reminiscent of clinical OA.