Figure 4.

The COMP content, regulation, and catabolism in arthritic joints. (A) COMP content is increased in the cartilage and synovium of arthritic joints, while COMP is decreased in the meniscus of late osteoarthritis (OA). COMP content is ubiquitously and uniformly distributed throughout all layers in healthy cartilage. In the early OA, COMP content is decreased in the damaged region while increased in the adjacent region. In the late OA with extensive cartilage destruction, the localization of COMP is limited within the superficial region; pronounced intracellular staining of COMP can be detected in this region. (B) COMP expression is regulated by mechanical loading, TGF-β1, IL-1β, and transcriptional repressor LRF. The combined regulation of multiple factors may be the mechanism of the dynamic expression of COMP in OA. Secreted COMP interacts with extracellular matrix (ECM) components that influence cell signaling events and functions as ECM feedback to chondrocytes. COMP content in ECM can be degraded by matrix-degrading proteinases, leading to the release and fragmentation of COMP and the increased flow into serum and synovial fluid. MMPs, matrix metalloproteinases; ADAMTS, a family of multidomain extracellular protease enzymes. Up or down arrows indicate the increase or decrease of COMP content. Question mark indicates undetermined.