title: The bone cell biology of osteogenesis imperfecta.
abstract: Osteogenesis Imperfecta (OI) has been defined as a heritable connective tissue disorder with variable severity of clinical expression. OI is a type I collagen based disease. Consequently, much research has focused on identifying specific mutations in the pro-alpha (I) genes. Our interest in OI lies in the metabolism of the non-collagenous proteins (NCPs) of the bone matrix. Although type I collagen is the most abundant protein in bone extracellular matrix, it is the NCPs which bind to, modify and have the potential to regulate that collagen matrix. Our approach has been to determine the levels of the NCPs for both OI and age-matched controls. Most recently, we have utilized an in vitro human osteoblast system to study normal and OI NCP metabolism (Fedarko et al. J. Bone Min. Res. 7, 921-930, 1992). It is our hypothesis that the altered stoichiometry of collagen and NCPs is, in part, responsible for the phenotypic variation of the disease.
authors.affiliation: Bone Research Branch, National Institute of Dental Research, NIH, Bethesda, MD, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Fedarko
authors.forename: U
authors.initials: U
authors.lastname: Vetter
authors.forename: P G
authors.initials: PG
authors.lastname: Robey
mesh_terms: D000818:Animals; D001846:Bone Development / Q000502:physiology*; D001857:Bone Matrix / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods; D003094:Collagen / Q000096:biosynthesis; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D010013:Osteogenesis Imperfecta / Q000378:metabolism* / Q000503:physiopathology; D011509:Proteoglycans / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D011509:Proteoglycans; D015675:Osteocalcin; D003094:Collagen