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Cartilage oligomeric matrix protein: COMPopathies and beyond.
Cartilage oligomeric matrix protein (COMP) is a large pentameric glycoprotein that interacts with multiple extracellular matrix proteins in cartilage and other tissues. While, COMP is known to play a role in collagen secretion and fibrillogenesis, chondrocyte proliferation and mechanical strength of tendons, the complete range of COMP functions remains to be defined. COMPopathies describe pseudoachondroplasia (PSACH) and multiple epiphyseal dysplasia (MED), two skeletal dysplasias caused by autosomal dominant COMP mutations. The majority of the mutations are in the calcium binding domains and compromise protein folding. COMPopathies are ER storage disorders in which the retention of COMP in the chondrocyte ER stimulates overwhelming cellular stress. The retention causes oxidative and inflammation processes leading to chondrocyte death and loss of long bone growth. In contrast, dysregulation of wild-type COMP expression is found in numerous diseases including: fibrosis, cardiomyopathy and breast and prostate cancers. The most exciting clinical application is the use of COMP as a biomarker for idiopathic pulmonary fibrosis and cartilage degeneration associated osteoarthritis and rheumatoid and, as a prognostic marker for joint injury. The ever expanding roles of COMP in single gene disorders and multifactorial diseases will lead to a better understanding of its functions in ECM and tissue homeostasis towards the goal of developing new therapeutic avenues.
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