The Extracellular Matrix in Genetic Skeletal Disorders

In this chapter, we review the current knowledge about the complex intracellular biosynthesis, secretion, and extracellular maturation of collagen I. We focus on the specific molecular roles of the numerous proteins involved in these processes and discuss how mutations in the encoding genes lead to alterations in the collagen I quality and/or quantity. We then provide an overview of the important role of collagen I in bone and in extraskeletal tissues. We use osteogenesis imper fecta as a prototype for collagen I-related diseases and address how changes in col lagen I quality and/or quantity affect the function of these tissues by providing specific examples based on observations made in patients and various animal mod els. This chapter shall hence provide a deeper understanding not only of the molecu lar basis of collagen I biochemistry but also of collagen I-related disorders and their diverse skeletal and extraskeletal manifestations.