Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice

T Xu; P Bianco; L W Fisher; G Longenecker; E Smith; S Goldstein; J Bonadio; A Boskey; Anne-Marie Heegaard; B Sommer; K Satomura; P Dominguez; C Zhao; A B Kulkarni; P G Robey; M F Young

doi:10.1038/1746

Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice

T Xu, P Bianco, L W Fisher, G Longenecker, E Smith, S Goldstein, J Bonadio, A Boskey, Anne-Marie Heegaard, B Sommer, K Satomura, P Dominguez, C Zhao, A B Kulkarni, P G Robey, M F Young

482 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	20
Issue number	1
Pages (from-to)	78-82
Number of pages	5
ISSN	1061-4036
DOIs	https://doi.org/10.1038/1746
Publication status	Published - 1998

Keywords

Age Factors
Animals
Biglycan
Bone Density
Bone Development
Bone and Bones
Extracellular Matrix Proteins
Female
Femur
Gene Expression Regulation, Developmental
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Osteoporosis
Phenotype
Proteoglycans
Tibia

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Xu, T., Bianco, P., Fisher, L. W., Longenecker, G., Smith, E., Goldstein, S., Bonadio, J., Boskey, A., Heegaard, A-M., Sommer, B., Satomura, K., Dominguez, P., Zhao, C., Kulkarni, A. B., Robey, P. G., & Young, M. F. (1998). Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice. Nature Genetics, 20(1), 78-82. https://doi.org/10.1038/1746

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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.",

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author = "T Xu and P Bianco and Fisher, {L W} and G Longenecker and E Smith and S Goldstein and J Bonadio and A Boskey and Anne-Marie Heegaard and B Sommer and K Satomura and P Dominguez and C Zhao and Kulkarni, {A B} and Robey, {P G} and Young, {M F}",

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AU - Xu, T

AU - Bianco, P

AU - Fisher, L W

AU - Longenecker, G

AU - Smith, E

AU - Goldstein, S

AU - Bonadio, J

AU - Boskey, A

AU - Heegaard, Anne-Marie

AU - Sommer, B

AU - Satomura, K

AU - Dominguez, P

AU - Zhao, C

AU - Kulkarni, A B

AU - Robey, P G

AU - Young, M F

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N2 - 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.

AB - 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.

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KW - Bone Development

KW - Bone and Bones

KW - Extracellular Matrix Proteins

KW - Female

KW - Femur

KW - Gene Expression Regulation, Developmental

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Osteoporosis

KW - Phenotype

KW - Proteoglycans

KW - Tibia

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JF - Nature: New biology

IS - 1

ER -

Targeted disruption of the biglycan gene leads to an osteoporosis-like phenotype in mice

Abstract

Keywords

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