Hydrostatic pressure-generated reactive oxygen species induce osteoarthritic conditions in cartilage pellet cultures

Osteoarthritis (OA) is one of the most common causes of disability and represents a major socioeconomic burden. Despite intensive  research, the molecular mechanisms responsible for the initiation and progression of OA remain inconclusive. In recent years  experimental findings revealed elevated levels of reactive oxygen species (ROS) as a major factor contributing to the onset and  progression of OA. Hence, we designed a hydrostatic pressure bioreactor system that is capable of stimulating cartilage cell cultures  with elevated ROS levels. Increased ROS levels in the media did not only lead to an inhibition of glycosaminoglycans and  collagen II formation but also to a reduction of already formed glycosaminoglycans and collagen II in chondrogenic mesenchymal  stem cell pellet cultures. These effects were associated with the elevated activity of matrix metalloproteinases as well as the  increased expression of several inflammatory cytokines. ROS activated different signaling pathways including PI3K/Akt and  MAPK/ERK which are known to be involved in OA initiation and progression. Utilizing the presented bioreactor system, an OA in  vitro model based on the generation of ROS was developed that enables the further investigation of ROS effects on cartilage  degradation but can also be used as a versatile tool for anti-oxidative drug testing.