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Neopeptides generated by the proteolysis of proteoglycans are recognized by specific neoepitope antibodies and can act as a proxy for the activity of certain proteases. Proteoglycan and proteoglycan fragments can be potentially used as prognostic, diagnostic, or theragnostic biomarkers for several diseases characterized by dysregulated extracellular matrix remodeling such as osteoarthritis, rheumatoid arthritis, atherosclerosis, thoracic aortic aneurysms, central nervous system disorders, viral infections, and cancer. 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