The effect of simulated microgravity on the osteo-articular system: an in vitro study of long-term culture of cartilage and bone tissue explants in the RCCSTM bioreactor

Long-term spaceflight affects almost all physiological systems in humans and considerable amount of data revealed its serious impact on skeletal homeostasis. While a microgravity environment has been proved to induce significant mineral loss and bone fragility (affecting, specifically, cancellous weight-bearing bones), its effect on articular cartilage (AC) is poorly known. AC is an avascular tissue, composed of relatively few mechanosensitive cells (chondrocytes), that synthesize a mechanically functional extracellular matrix (ECM), composed of collagen, proteoglycans and other proteins. In response to physical factors (e.g. pressure and deformation) chondrocytes regulate AC histomorphology and function, and may affect bone tissue homeostasis. It is then likely that the absence of gravitational load should alter chondrocytes’ activity. In the present study we investigated, in vitro, the effect of long-term exposure to a simulated microgravity condition (vector-averaged gravity) on whole explants of cancellous bone (rat tibial proximal epiphyses) and AC tissue (newborn rabbit knee’s joint). Tissue explants were kept in culture for up to 4 weeks by the use of the Rotary Cell Culture System (RCCSTM) bioreactor, the unique device, operating on the Earth’s surface, capable of successfully simulate a microgravity environment. The analysis of the structural/mechanical properties of cancellous bone explants was performed by a numerical model based on the Cell Method, applied to the 3D reconstruction of micro-computed tomography scans of the bone samples. With regard to AC tissue, functional and structural properties were studied by comparative cell viability, histochemical and molecular analyses performed on either the cellular component or on their ECM. The results obtained demonstrate that, while our RCCSTM-based culture system is able to preserve native tissue architecture and cells’ viability all during the experimental procedure, long-term exposure to a microgravity environment may effectively alter bone cells’ and articular chondrocytes’ physiology.