title: Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice.
abstract: The resilience and strength of bone is due to the orderly mineralization of a specialized extracellular matrix (ECM) composed of type I collagen (90%) and a host of non-collagenous proteins that are, in general, also found in other tissues. Biglycan (encoded by the gene Bgn) is an ECM proteoglycan that is enriched in bone and other non-skeletal connective tissues. In vitro studies indicate that Bgn may function in connective tissue metabolism by binding to collagen fibrils and TGF-beta (refs 5,6), and may promote neuronal survival. To study the role of Bgn in vivo, we generated Bgn-deficient mice. Although apparently normal at birth, these mice display a phenotype characterized by a reduced growth rate and decreased bone mass due to the absence of Bgn. To our knowledge, this is the first report in which deficiency of a non-collagenous ECM protein leads to a skeletal phenotype that is marked by low bone mass that becomes more obvious with age. These mice may serve as an animal model to study the role of ECM proteins in osteoporosis.
authors.affiliation: Craniofacial and Skeletal Diseases Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: T
authors.initials: T
authors.lastname: Xu
authors.forename: P
authors.initials: P
authors.lastname: Bianco
authors.forename: L W
authors.initials: LW
authors.lastname: Fisher
authors.forename: G
authors.initials: G
authors.lastname: Longenecker
authors.forename: E
authors.initials: E
authors.lastname: Smith
authors.forename: S
authors.initials: S
authors.lastname: Goldstein
authors.forename: J
authors.initials: J
authors.lastname: Bonadio
authors.forename: A
authors.initials: A
authors.lastname: Boskey
authors.forename: A M
authors.initials: AM
authors.lastname: Heegaard
authors.forename: B
authors.initials: B
authors.lastname: Sommer
authors.forename: K
authors.initials: K
authors.lastname: Satomura
authors.forename: P
authors.initials: P
authors.lastname: Dominguez
authors.forename: C
authors.initials: C
authors.lastname: Zhao
authors.forename: A B
authors.initials: AB
authors.lastname: Kulkarni
authors.forename: P G
authors.initials: PG
authors.lastname: Robey
authors.forename: M F
authors.initials: MF
authors.lastname: Young
mesh_terms: D000367:Age Factors; D000818:Animals; D058578:Biglycan; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D001846:Bone Development; D001842:Bone and Bones / Q000473:pathology*; D016326:Extracellular Matrix Proteins; D005260:Female; D005269:Femur / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010024:Osteoporosis / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011509:Proteoglycans / Q000235:genetics* / Q000502:physiology*; D013977:Tibia / Q000473:pathology
chemical_list: C546885:Bgn protein, mouse; D058578:Biglycan; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans