A systems biology approach to synovial joint lubrication in health, injury, and disease

Abstract

The synovial joint contains synovial fluid (SF) within a cavity bounded by articular cartilage and synovium. SF is a viscous fluid that has lubrication, metabolic, and regulatory functions within synovial joints. SF contains lubricant molecules, including proteoglycan-4 and hyaluronan. SF is an ultrafiltrate of plasma with secreted contributions from cell populations lining and within the synovial joint space, including chondrocytes and synoviocytes. Maintenance of normal SF lubricant composition and function are important for joint homeostasis. In osteoarthritis, rheumatoid arthritis, and joint injury, changes in lubricant composition and function accompany alterations in the cytokine and growth factor environment and increased fluid and molecular transport through joint tissues. Thus, understanding the synovial joint lubrication system requires a multifaceted study of the various parts of the synovial joint and their interactions. Systems biology approaches at multiple scales are being used to describe the molecular, cellular, and tissue components and their interactions that comprise the functioning synovial joint. Analyses of the transcriptome and proteome of SF, cartilage, and synovium suggest that particular molecules and pathways play important roles in joint homeostasis and disease. Such information may be integrated with physicochemical tissue descriptions to construct integrative models of the synovial joint that ultimately may explain maintenance of health, recovery from injury, or development and progression of arthritis.

Figure 1

Joint injury and disease involve pathologic changes in multiple joint tissues. Schematic view of synovial joint tissue changes in (B) OA, (C) RA, and (D) injury, compared to (A) a normal, healthy joint. Notched, outlined arrows represent fluid flows from vasculature to SF, and from SF to lymphatics. Undulating arrows represent secretion of lubricant molecules HA and PRG4 into SF. The relative sizes of arrows indicate relative magnitudes of flows and secretions. For example, increased flow from the vasculature to SF in (D) injury compared to (A) normal is represented by an orange, notched, outlined arrow that is larger in (D) injury compared to (A) normal. Up-arrows indicate increases in concentrations of the various substances. McCarty WJ, Nguyen QT, Hui AY, Chen AC, Sah RL. Synovial Joints: Mechanobiology and Tissue Engineering of Articular Cartilage and Synovial Fluid. In: Ducheyne P, Healy KE, Hutmacher DE, Grainger DE, Kirkpatrick CJ, eds. Comprehensive Biomaterials. 1st ed; 2011.