Molecular genetics of the cartilage collagenopathies

Abstract

The cartilage extracellular matrix is rich in fibrillar- and fibril-associated collagens, and mutations in these collagen genes cause a wide range of chondrodysplasias, ranging from premature arthritis through to severe early lethal disorders. Collagen mutations can interfere with matrix organisation and cause cartilage dysfunction by reducing synthesis of structurally normal protein, or through protein misfolding which leads to intracellular retention and degradation, and consequent secretion of reduced amounts of structurally abnormal protein. In addition, collagen misfolding mutations can induce a cellular unfolded protein response which can alter chondrocyte differentiation and ultimatel..