Synovial joint organ homeostasis: mechanisms and biological considerations.

Synovial joints are complex multi-tissue organs that permit movement. A well-functioning synovial joint relies on complex interconnected homeostatic mechanisms to maintain joint organ function in response to biomechanical and metabolic demands. These homeostatic mechanisms include, but are not limited to, appropriate mechanobiological responses to load, nutrient delivery from its vasculature, lubrication, proprioception and pain, immunosurveillance, and maintenance of the extracellular matrix (ECM) composition. In osteoarthritis (OA), joint homeostasis is chronically deranged leading to failure of the synovial joint organ and impairment or loss of function. Maintaining synovial joint organ homeostasis is therefore critical to joint function and relies on complex interconnected physiological process at the joint level. As OA prevalence continues to rise, deepening our understanding of the integrated systems that sustain joint homeostasis may identify fruitful avenues for therapeutic intervention. However, key knowledge gaps will need to be addressed including, characterizing vessel function in joint diseases, understanding the role of novel proteases in ECM catabolism, and determining the role of non-macrophage synovial immune cells in joint immunosurveillance. We believe that future research will find greater success if these homeostatic mechanisms are viewed as a single integrated system that considers the crosstalk between mechanical, vascular, immune, and biochemical factors. Therefore, in this review, we explore the interconnected mechanisms that support joint homeostasis and how dysregulation can lead to failure of the synovial joint organ.