Chondrocyte Homeostasis and Differentiation: Transcriptional Control and Signaling in Healthy and Osteoarthritic Conditions

Chondrocytes are the main cell type in articular cartilage. They are embedded in an avascular, abundant, and specialized extracellular matrix (ECM). Chondrocytes are responsible for the synthesis and turnover of the ECM, in which the major macromolecular components are collagen, proteoglycans, and non-collagen proteins. The crosstalk between chondrocytes and the ECM plays several relevant roles in the regulation of cell phenotype. Chondrocytes live in an avascular environment in healthy cartilage with a low oxygen supply. Although chondrocytes are adapted to anaerobic conditions, many of their metabolic functions are oxygen-dependent, and most cartilage oxygen is supplied by the synovial fluid. This review focuses on the transcription control and signaling responsible for chondrocyte differentiation, homeostasis, senescence, and cell death and the changes that occur in osteoarthritis. The effects of chondroitin sulfate and other molecules as anti-inflammatory agents are also approached and analyzed.