Extracellular Matrix Fragments as Regulators of Cartilage Metabolism in Health and Disease
Gene A. Homandberg,
It is now firmly established that fragments of extracellular matrix (ECM) macromolecules that arise from the damaged ECM have the ability to regulate chondrocyte metabolism and enhance the degradative processes. Fibronectin fragments (Fn-fs), type II collagen fragments (Col-fs) and hyaluronan fragments (HA-fs) have all been shown to upregulate matrix metalloproteinases and cause extensive damage to the ECM, while Fn-fs have also been shown to enhance anabolic pathways. Since these ECM fragments are elevated in states of cartilage degeneration or in osteoarthritic cartilage, the ECM fragments likely play a role in either initiation or augmentation of degradative and anabolic pathways which collectively dictate the metabolic state of the damaged tissue. Retrospectively, the ability of ECM fragments to serve as the initial sensors of cartilage damage provides the most upstream signaling possible for effective cartilage repair/ remodeling. Newer observations suggest that the perturbation of the matrix to chondrocyte interactions by ECM fragments may be the key initiating event in the catabolic pathways since this may indirectly affect matrix to receptor interaction and downstream signaling. It is conceivable that these fragment pathways either intersect or overlap and involve common players which might constitute common targets for therapeutic intervention.
Keywords: Osteoarthritis, fibronectin, fibronectin fragments, cartilage, matrix
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