Extracellular Vesicles in Synovial Fluid: Their Role in Joint Homeostasis and Pathophysiology

Synovial fluid is a crucial component of joints. It serves as lubricant of articular cartilage and nutrient source for articular structures including cartilage and meniscus. The synovial fluid is produced by the synovial membrane and is made of polymers including hyaluronan, lubricin, proteinase, collagenases, and prostaglandins. Being populated by immune cells and floating stromal components and being in contact with the articular tissues, the synovial fluid is populated by different classes of extracellular vesicles (EVs). EVs can be free or entrapped in the network through physical binding with hyaluronan and the other polymers. Thus, their movement and shuttling between cells and tissues is tightly regulated and part of the mechanisms allowing joints component to communicate. For this reason, alteration in joint tissues under stress or pathological conditions may alter EVs composition and communication and these changes may be useful as biomarkers for the disease. Moreover, in recent years, EVs released from mesenchymal stromal cells (MSCs) have been envisioned as potential therapeutic agents, due to the anti-inflammatory and pro-regenerative features mirrored from their releasing cells. An active debate is also undergoing to find the most powerful way of EVs administration, using new-generation scaffolds as vehicle to protect EVs from degradation and therefore to prolong their therapeutic activity. Thus, synovial fluid and EVs, both endogenous and administered, are crucial actors for joint homeostasis and therapy.