title: Genetic causes and mechanisms of Osteogenesis Imperfecta.
abstract: Osteogenesis Imperfecta (OI) is a genetic disorder characterized by various clinical features including bone deformities, low bone mass, brittle bones, and connective tissue manifestations. The predominant cause of OI is due to mutations in the two genes that encode type I collagen. However, recent advances in sequencing technology has led to the discovery of novel genes that are implicated in recessive and dominant OI. These include genes that regulate the post-translational modification, secretion and processing of type I collagen as well as those required for osteoblast differentiation and bone mineralization. As such, OI has become a spectrum of genetic disorders informing about the determinants of both bone quantity and quality. Here we summarize the known genetic causes of OI, animal models that recapitulate the human disease and mechanisms that underlie disease pathogenesis. Additionally, we discuss the effects of disrupted collagen networks on extracellular matrix signaling and its impact on disease progression.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Joohyun
authors.initials: J
authors.lastname: Lim
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Ingo
authors.initials: I
authors.lastname: Grafe
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Alexander
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: blee@bcm.edu.
authors.forename: Brendan
authors.initials: B
authors.lastname: Lee
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic; D003094:Collagen / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D020022:Genetic Predisposition to Disease; D006801:Humans; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D011499:Protein Processing, Post-Translational
chemical_list: D003094:Collagen
keywords: Collagen type I; Extracellular matrix; Osteoblast; Osteogenesis Imperfecta; TGF-β signaling