ldl receptor related proteins

Summary

Summary: A family of proteins that share sequence similarity with the low density lipoprotein receptor (RECEPTORS, LDL).

Top Publications

  1. ncbi LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development
    Y Gong
    Cell 107:513-23. 2001
  2. ncbi High bone density due to a mutation in LDL-receptor-related protein 5
    Lynn M Boyden
    Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    N Engl J Med 346:1513-21. 2002
  3. ncbi Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation
    Josipa Bilic
    Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Science 316:1619-22. 2007
  4. ncbi Function and biological roles of the Dickkopf family of Wnt modulators
    C Niehrs
    Department of Molecular Embryology, German Cancer Research Center, Heidelberg, Germany
    Oncogene 25:7469-81. 2006
  5. pmc LRP6 mutation in a family with early coronary disease and metabolic risk factors
    Arya Mani
    Department of Internal Medicine, Howard Hughes Medical Institute and Yale University School of Medicine, New Haven, CT 06510, USA
    Science 315:1278-82. 2007
  6. pmc Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q
    Carmel Toomes
    Molecular Medicine Unit, University of Leeds, Leeds, United Kingdom
    Am J Hum Genet 74:721-30. 2004
  7. pmc Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion
    Takahiro Fujino
    Gene Research Center and Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University, Sendai 980 8574, Japan
    Proc Natl Acad Sci U S A 100:229-34. 2003
  8. pmc Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density
    Liesbeth Van Wesenbeeck
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Am J Hum Genet 72:763-71. 2003
  9. pmc A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait
    Randall D Little
    Department of Human Genetics, Genome Therapeutics Corporation, Waltham, MA 02453, USA
    Am J Hum Genet 70:11-9. 2002
  10. pmc Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor
    Masaki Kato
    Department of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    J Cell Biol 157:303-14. 2002

Research Grants

Detail Information

Publications189 found, 100 shown here

  1. ncbi LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development
    Y Gong
    Cell 107:513-23. 2001
    ..These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass...
  2. ncbi High bone density due to a mutation in LDL-receptor-related protein 5
    Lynn M Boyden
    Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    N Engl J Med 346:1513-21. 2002
    ..Loss-of-function mutations in the gene for low-density lipoprotein receptor-related protein 5 (LRP5), which acts in the Wnt signaling pathway, have been shown to cause osteoporosis-pseudoglioma...
  3. ncbi Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation
    Josipa Bilic
    Division of Molecular Embryology, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D 69120 Heidelberg, Germany
    Science 316:1619-22. 2007
    ..We propose that Wnts induce coclustering of receptors and Dvl in LRP6-signalosomes, which in turn triggers LRP6 phosphorylation to promote Axin recruitment and beta-catenin stabilization...
  4. ncbi Function and biological roles of the Dickkopf family of Wnt modulators
    C Niehrs
    Department of Molecular Embryology, German Cancer Research Center, Heidelberg, Germany
    Oncogene 25:7469-81. 2006
    ..In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer's disease...
  5. pmc LRP6 mutation in a family with early coronary disease and metabolic risk factors
    Arya Mani
    Department of Internal Medicine, Howard Hughes Medical Institute and Yale University School of Medicine, New Haven, CT 06510, USA
    Science 315:1278-82. 2007
    ..These results link a single gene defect in Wnt signaling to CAD and multiple cardiovascular risk factors...
  6. pmc Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q
    Carmel Toomes
    Molecular Medicine Unit, University of Leeds, Leeds, United Kingdom
    Am J Hum Genet 74:721-30. 2004
    ..This finding further underlines the significance of Wnt signaling in the vascularization of the eye and highlights the potential dangers of using multiple families to refine genetic intervals in gene-identification studies...
  7. pmc Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion
    Takahiro Fujino
    Gene Research Center and Division of Nephrology, Endocrinology, and Vascular Medicine, Department of Medicine, Tohoku University, Sendai 980 8574, Japan
    Proc Natl Acad Sci U S A 100:229-34. 2003
    ..In contrast, LRP5-deficient islets lacked the Wnt-3a-stimulated insulin secretion. These data suggest that WntLRP5 signaling contributes to the glucose-induced insulin secretion in the islets...
  8. pmc Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density
    Liesbeth Van Wesenbeeck
    Department of Medical Genetics, University of Antwerp, Antwerp, Belgium
    Am J Hum Genet 72:763-71. 2003
    ..Functional analysis of the effects of the various mutations will be of interest, to evaluate whether all the mutations give rise to the same pathogenic mechanism...
  9. pmc A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait
    Randall D Little
    Department of Human Genetics, Genome Therapeutics Corporation, Waltham, MA 02453, USA
    Am J Hum Genet 70:11-9. 2002
    ..Our findings suggest that the HBM mutation confers a unique osteogenic activity in bone remodeling, and this understanding may facilitate the development of novel therapies for the treatment of osteoporosis...
  10. pmc Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor
    Masaki Kato
    Department of Molecular and Cellular Biology and Medicine, Baylor College of Medicine, Houston, TX 77030, USA
    J Cell Biol 157:303-14. 2002
    ..Moreover, these features recapitulate human osteoporosis-pseudoglioma syndrome, caused by LRP5 inactivation...
  11. ncbi LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way
    Xi He
    Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
    Development 131:1663-77. 2004
    ..We also discuss the regulation of Lrp5/Lrp6 by other extracellular ligands, and LRP5 mutations associated with familial osteoporosis and other disorders...
  12. ncbi Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway
    J Mao
    Department of Genetics and Developmental Biology, University of Connecticut, Farmington, CT 06030, USA
    Mol Cell 7:801-9. 2001
    ..In addition, the LRP-5 sequences involved in interactions with Axin are required for LEF-1 activation. Thus, we conclude that the binding of Axin to LRP-5 is an important part of the Wnt signal transduction pathway...
  13. ncbi Wnt signals across the plasma membrane to activate the beta-catenin pathway by forming oligomers containing its receptors, Frizzled and LRP
    Feng Cong
    Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Development 131:5103-15. 2004
    ..In addition, the beta-catenin signaling mediated by ectopic expression of LRP is not dependent on Disheveled or Wnt, but can also be augmented by oligomerization of LRP receptors...
  14. pmc The Wnt co-receptor Lrp6 is required for normal mouse mammary gland development
    Charlotta Lindvall
    Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan, United States of America
    PLoS ONE 4:e5813. 2009
    ..In humans, increased Lrp6 expression is associated with basal-like breast cancer. Taken together, our results suggest both overlapping and specific functions for Lrp5 and Lrp6 in the mammary gland...
  15. ncbi Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation
    Donald A Glass
    Department of Molecular and Human Genetics, Bone Disease Program of Texas, Houston, 77030, USA
    Dev Cell 8:751-64. 2005
    ....
  16. pmc N-cadherin interacts with axin and LRP5 to negatively regulate Wnt/beta-catenin signaling, osteoblast function, and bone formation
    Eric Hay
    INSERM, U606, Paris, France
    Mol Cell Biol 29:953-64. 2009
    ..These data indicate that a previously unrecognized N-cadherin-axin-LRP5 interaction negatively regulates Wnt/beta-catenin signaling and is critical in the regulation of osteoblast function, bone formation, and bone mass...
  17. ncbi LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women
    Sylvie Giroux
    Unite de Recherche en Genetique Humaine et Moleculaire, Centre de Recherche de l Hôpital St François d Assise du Centre Hospitalier Universitaire de Québec, Quebec, Canada G1L 3L5
    Bone 40:1299-307. 2007
    ..Mutations associated with gain-of-function were described as well as loss-of-function mutations. Following this discovery, many frequent LRP5 polymorphisms were tested against the variation of BMD in the normal population...
  18. pmc Wnt3a-mediated formation of phosphatidylinositol 4,5-bisphosphate regulates LRP6 phosphorylation
    Weijun Pan
    Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06510, USA
    Science 321:1350-3. 2008
    ..In turn, PtdIns (4,5)P2 regulated phosphorylation of LRP6 at Thr1479 and Ser1490. Therefore, our study reveals a signaling mechanism for Wnt to regulate LRP6 phosphorylation...
  19. ncbi Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling
    Xiaofeng Li
    Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, 06030, USA
    J Biol Chem 280:19883-7. 2005
    ....
  20. pmc The LRP5 high-bone-mass G171V mutation disrupts LRP5 interaction with Mesd
    Yazhou Zhang
    Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Ave, Farmington, CT 06410, USA
    Mol Cell Biol 24:4677-84. 2004
    ....
  21. pmc Reduced affinity to and inhibition by DKK1 form a common mechanism by which high bone mass-associated missense mutations in LRP5 affect canonical Wnt signaling
    Minrong Ai
    Department of Genetics and Center for Human Genetics, Case School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106, USA
    Mol Cell Biol 25:4946-55. 2005
    ....
  22. ncbi Role of the intracellular domains of LRP5 and LRP6 in activating the Wnt canonical pathway
    Kaihong Mi
    Department of Psychiatry, University of Alabama at Birmingham, Alabama 35294 0017, USA
    J Cell Biochem 95:328-38. 2005
    ..These findings provide significant new insights into the roles of LRP5/6 in modulating canonical Wnt signaling...
  23. pmc Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice
    Philippe Clément-Lacroix
    Prostrakan Pharmaceuticals, 102 route de Noisy, 93230 Romainville, France
    Proc Natl Acad Sci U S A 102:17406-11. 2005
    ..Lithium has been used safely and effectively for over half a century in the treatment of bipolar illness. Prospective studies in patients receiving lithium should determine whether it also improves bone mass in humans...
  24. ncbi Patients with high bone mass phenotype exhibit enhanced osteoblast differentiation and inhibition of adipogenesis of human mesenchymal stem cells
    Weimin Qiu
    Laboratory for Molecular Endocrinology KMEB, Department of Endocrinology and Metabolism, University Hospital of Odense, Odense C, Denmark
    J Bone Miner Res 22:1720-31. 2007
    ..Our in vivo and in vitro results show that activated mutation T253I of LRP5 enhances osteogenesis and inhibits adipogenesis. Inactivating mutation T244M of LRP5 exerts opposite effects...
  25. ncbi BMP-2 controls alkaline phosphatase expression and osteoblast mineralization by a Wnt autocrine loop
    Georges Rawadi
    Proskelia Pharmaceuticals, Romainville, France
    J Bone Miner Res 18:1842-53. 2003
    ..The precise role of this cascade in osteoblast differentiation was examined. We show that a Wnt autocrine loop mediates the induction of alkaline phosphatase and mineralization by BMP-2 in pre-osteoblastic cells...
  26. pmc Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with peak bone mass in non-sedentary men: results from the Odense androgen study
    K Brixen
    Department of Endocrinology, Odense University Hospital, 5000, Odense C, Denmark
    Calcif Tissue Int 81:421-9. 2007
    ..To investigate the impact of the Ala1330Val (rs3736228, exon 18) and Val667Met (rs4988321, exon 9) polymorphisms of the low-density lipoprotein receptor-related protein 5 (LRP5) gene on peak bone mass in young men...
  27. ncbi Influence of LRP5 polymorphisms on normal variation in BMD
    M Audrey Koay
    Institute of Musculoskeletal Sciences, University of Oxford, The Botnar Research Centre, Nuffield Orthopaedic Centre, Headington, Oxford, UK
    J Bone Miner Res 19:1619-27. 2004
    ....
  28. pmc Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization
    Xin Ye
    Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 139:285-98. 2009
    ....
  29. ncbi Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes
    Minghui Qin
    Division of Genome Analysis, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
    Hum Mutat 26:104-12. 2005
    ..The profile of the mutations obtained in the current study further illustrates the complexity of the disease and provides a better understanding of the spectrum, frequencies, and genotype-phenotype correlation...
  30. pmc Clinical and molecular findings in osteoporosis-pseudoglioma syndrome
    Minrong Ai
    Department of Genetics and Center for Human Genetics, Case School of Medicine and University Hospitals of Cleveland, Cleveland, OH, 44106, USA
    Am J Hum Genet 77:741-53. 2005
    ..These results indicate that early bilateral vitreoretinal eye pathology coupled with skeletal fragility is a strong predictor of LRP5 mutation and that mutations in LRP5 cause OPPG by impairing Wnt and Norrin signal transduction...
  31. ncbi Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity
    Jen Chih Hsieh
    Department of Biochemistry and Cell Biology, Center for Developmental Genetics, State University of New York, Stony Brook, Stony Brook, NY 11794, USA
    Cell 112:355-67. 2003
    ....
  32. ncbi Expression of LDL receptor-related protein 5 (LRP5) as a novel marker for disease progression in high-grade osteosarcoma
    Bang H Hoang
    Department of Surgery, Orthopaedic Surgery Service, affiliated with Weill Medical College of Cornell University, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Int J Cancer 109:106-11. 2004
    ..These results showed that expression of LRP5 is a common event in OS and strongly suggest a role for LRP and Wnt signaling in the pathobiology and progression of this disease...
  33. ncbi Novel LRP5 missense mutation in a patient with a high bone mass phenotype results in decreased DKK1-mediated inhibition of Wnt signaling
    Wendy Balemans
    Department of Medical Genetics, University and University Hospital of Antwerp, Antwerp, Belgium
    J Bone Miner Res 22:708-16. 2007
    ..In vitro studies suggest that a reduced antagonistic effect of DKK1 on canonical Wnt signaling contributes to the molecular effect of this mutation and its pathogenic consequence...
  34. ncbi WNT signaling in stem cell biology and regenerative medicine
    Masaru Katoh
    Genetics and Cell Biology Section, National Cancer Center Research Institute, Tokyo 104 0045, Japan
    Curr Drug Targets 9:565-70. 2008
    ..Recombinant WNT protein or WNT mimetic (circular peptide, small molecule compound, or RNA aptamer) in combination with Notch mimetic, FGF protein, and BMP protein opens a new window to tissue engineering for regenerative medicine...
  35. pmc R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6
    Minke E Binnerts
    Nuvelo, Inc, 201 Industrial Road, Suite 310, San Carlos, CA 94070 6211, USA
    Proc Natl Acad Sci U S A 104:14700-5. 2007
    ..Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Wnt pathway...
  36. pmc Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum
    Vijay K Yadav
    Department of Genetics and Development, Columbia University, New York, NY 10032, USA
    Cell 135:825-37. 2008
    ..By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner, this study broadens our understanding of bone remodeling and suggests potential therapies to increase bone mass...
  37. ncbi Wnt signaling and osteoblastogenesis
    Peter V N Bodine
    Women s Heath and Musculoskeletal Biology, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA
    Rev Endocr Metab Disord 7:33-9. 2006
    ....
  38. pmc Wnt signaling as a therapeutic target for bone diseases
    Luke H Hoeppner
    Graduate Program in Microbiology, Immunology and Cancer Biology, University of Minnesota, Minneapolis, MN, USA
    Expert Opin Ther Targets 13:485-96. 2009
    ..There is a need to develop new bone anabolic agents because current bone regeneration regimens have limitations. The Wingless-type MMTV integration site (Wnt) pathway has emerged as a regulator of bone formation and regeneration...
  39. ncbi Lrp6 hypomorphic mutation affects bone mass through bone resorption in mice and impairs interaction with Mesd
    Takuo Kubota
    Department of Pediatrics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
    J Bone Miner Res 23:1661-71. 2008
    ..These results indicate that Lrp6-mediated signaling controls postnatal bone mass, at least partly through the regulation of bone resorption. It is also suggested that the interaction with Mesd is critical for Lrp6 to function...
  40. pmc The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo
    Vitezslav Bryja
    Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Center for Developmental Biology and Regenerative Medicine, Karolinska Institute, SE 171 77 Stockholm, Sweden
    Mol Biol Cell 20:924-36. 2009
    ..Thus, we provide evidence that the extracellular domains of Lrp5/6 behave as physiologically relevant inhibitors of noncanonical Wnt signaling during Xenopus and mouse development in vivo...
  41. ncbi Patients with high-bone-mass phenotype owing to Lrp5-T253I mutation have low plasma levels of serotonin
    Morten Frost
    Department of Endocrinology and Metabolism, Laboratory for Molecular Endocrinology KMEB, Medical Biotechnology Centre, University of Southern Denmark, Odense, Denmark
    J Bone Miner Res 25:673-5. 2010
    ..16 +/- 0.28 ng/mL versus 3.51 +/- 0.49 ng/mL, respectively, p < .05). Our data support the hypothesis that circulating serotonin levels mediate the increased bone mass resulting from gain-of-function mutations in Lrp5 in humans...
  42. ncbi Genetic analysis of Lrp5 function in osteoblast progenitors
    Vijay K Yadav
    Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA
    Calcif Tissue Int 86:382-8. 2010
    ..These results rule out a direct function of Lrp5 in osteoblast progenitor cells and add further support to the notion that dysregulation of serotonin synthesis is involved in bone mass abnormalities observed in OPPG patients...
  43. ncbi Targeting the Wnt/beta-catenin pathway to regulate bone formation in the adult skeleton
    Roland Baron
    Yale University School of Medicine, 333 Cedar Street, P O Box 208044, New Haven, CT 06520 8044, USA
    Endocrinology 148:2635-43. 2007
    ..Multiple genetic and pharmacological manipulations of Wnt signaling in mice have since then confirmed the central role of this pathway in regulating bone formation...
  44. ncbi Lrp5 and bone formation : A serotonin-dependent pathway
    Vijay K Yadav
    Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York, USA
    Ann N Y Acad Sci 1192:103-9. 2010
    ..These findings may have important therapeutic implications for the treatment of low bone-mass disorders...
  45. ncbi Low density lipoprotein receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia
    Anne Saarinen
    Folkhalsan Institute of Genetics, University of Helsinki, Helsinki, Finland
    Clin Endocrinol (Oxf) 72:481-8. 2010
    ..Animal models implicate a role for LRP5 in lipid and glucose homeostasis. The objective was to evaluate metabolic consequences of LRP5 mutations in humans...
  46. pmc Where Wnts went: the exploding field of Lrp5 and Lrp6 signaling in bone
    Bart O Williams
    Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
    J Bone Miner Res 24:171-8. 2009
    ....
  47. ncbi Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites
    Dong Hai Xiong
    Osteoporosis Research Center and Department of Biomedical Sciences, Creighton University, Omaha, NE, USA
    J Bone Miner Res 22:385-93. 2007
    ..These data support the concept that LRP5 variation can contribute to minor and major variation in bone structure...
  48. pmc Haplotype structure, LD blocks, and uneven recombination within the LRP5 gene
    Rebecca C J Twells
    JDRF WT Diabetes and Inflammation Laboratory, Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 2XY, UK
    Genome Res 13:845-55. 2003
    ..The identification of hot spots in between these LD blocks provides additional evidence that LD blocks are separated by areas of higher recombination...
  49. ncbi Bone density ligand, Sclerostin, directly interacts with LRP5 but not LRP5G171V to modulate Wnt activity
    Debra L Ellies
    Stowers Institute for Medical Research, Kansa City, Missouri 64110, USA
    J Bone Miner Res 21:1738-49. 2006
    ..Our data suggest that functional interactions between Sost or Wise and LRP5/LRP6 have the potential to regulate bone deposition by modulating the Wnt pathway...
  50. ncbi Localization of the gene causing autosomal dominant osteopetrosis type I to chromosome 11q12-13
    Els Van Hul
    Department of Medical Genetics, University of Antwerp, Belgium
    J Bone Miner Res 17:1111-7. 2002
    ..Because both genes map within the candidate region for ADOI, it can not be excluded that ADOI is caused by mutations in either the TCIRG1 or the LRP5 gene...
  51. ncbi Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6
    M V Semenov
    Division of Neuroscience, Children s Hospital, Department of Neurology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA
    Curr Biol 11:951-61. 2001
    ..The significance of the Fz-LRP6 complex in signal transduction remains to be established...
  52. ncbi Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin
    Alexander G Robling
    Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Biol Chem 283:5866-75. 2008
    ....
  53. pmc Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6
    Bryan T MacDonald
    F M Kirby Neurobiology Center, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 283:16115-23. 2008
    ....
  54. ncbi Cloning of a novel member of the low-density lipoprotein receptor family
    P J Hey
    Merck Research Laboratories, Department of Human Genetics, West Point, PA 19486, USA
    Gene 216:103-11. 1998
    ..Both human and mouse LRP5 cDNAs have been isolated and the encoded mature proteins are 95% identical, indicating a high degree of evolutionary conservation...
  55. ncbi SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor
    Mikhail Semenov
    Division of Neuroscience, Children s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Biol Chem 280:26770-5. 2005
    ..Our findings suggest that SOST is an antagonist for Wnt signaling and that the loss of SOST function likely leads to the hyperactivation of Wnt signaling that underlies bone overgrowth seen in sclerosteosis patients...
  56. ncbi The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice
    Olivia G Kelly
    Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA 94720 3200, USA
    Development 131:2803-15. 2004
    ..The effect of reducing, but not eliminating, Wnt signaling in Lrp5(+/-);Lrp6(-/-) mutant embryos provides important insight into the interplay between Wnt, Fgf and Nodal signals in patterning the early mouse embryo...
  57. ncbi Wise retained in the endoplasmic reticulum inhibits Wnt signaling by reducing cell surface LRP6
    Sonia Guidato
    Division of Developmental Neurobiology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK
    Dev Biol 310:250-63. 2007
    ..This study provides a cellular mechanism for the action of Wise and introduces the modulation of cellular susceptibility to Wnt signals as a novel mechanism of the regulation of the Wnt pathway...
  58. ncbi Wnt signaling: a key regulator of bone mass
    Roland Baron
    Yale University School of Medicine New Haven, Connecticut 06520, USA
    Curr Top Dev Biol 76:103-27. 2006
    ....
  59. ncbi The low density lipoprotein receptor-related protein 6 interacts with glycogen synthase kinase 3 and attenuates activity
    Kaihong Mi
    Department of Psychiatry, University of Alabama at Birmingham, Birmingham, Alabama 35294 0017, USA
    J Biol Chem 281:4787-94. 2006
    ..This is the first identification of a direct interaction between LRP6 and GSK3, which results in an attenuation of GSK3 activity...
  60. ncbi LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders
    Regis Levasseur
    Rheumatology Department, Angers Teaching Hospital, 49933 Angers Cedex 9, France
    Joint Bone Spine 72:207-14. 2005
    ....
  61. ncbi Bone biomechanical properties in LRP5 mutant mice
    M P Akhter
    Osteoporosis Research Center, Creighton University, Omaha, NE 68131, USA
    Bone 35:162-9. 2004
    ..Despite similar body weight to NTG mice, the denser and stiffer bones in G171V mice may represent greater bone formation sensitivity to normal mechanical stimuli resulting in an overadaptation of skeleton to weight-related forces...
  62. ncbi Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density
    Tomohiko Urano
    Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, 113 8655, Tokyo, Japan
    J Bone Miner Metab 22:341-5. 2004
    ..02 +/- 1.42; P = 0.013). These findings suggest that the LRP5 gene is a candidate for the genetic determinants of BMD in postmenopausal women, and this SNP could be useful as a genetic marker for predicting the risk of osteoporosis...
  63. pmc DKK1 antagonizes Wnt signaling without promotion of LRP6 internalization and degradation
    Mikhail V Semenov
    F M Kirby Neurobiology Center, Children s Hospital Boston and Department of Neurology, Harvard Medical School, 61 Binney Street, Boston, MA 02115, USA
    J Biol Chem 283:21427-32. 2008
    ..7 h) of LRP6. We conclude that DKK1 inhibition of LRP6 is independent of LRP6 internalization and degradation...
  64. pmc Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites
    Serge L Ferrari
    Division of Bone Diseases, University Hospital of Geneva, Geneva 1211, Switzerland
    Am J Hum Genet 74:866-75. 2004
    ..Together, these results suggest that LRP5 variants significantly contribute to LS-bone-mass and size determination in men by influencing vertebral bone growth during childhood...
  65. ncbi Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair
    Qiang Xu
    Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
    Cell 116:883-95. 2004
    ..These data define a Norrin-Fz4 signaling system that plays a central role in vascular development in the eye and ear, and they indicate that ligands unrelated to Wnts can act through Fz receptors...
  66. pmc Characterization of the Kremen-binding site on Dkk1 and elucidation of the role of Kremen in Dkk-mediated Wnt antagonism
    Ke Wang
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China
    J Biol Chem 283:23371-5. 2008
    ..These results suggest that Kremen may not be essential for Dkk1-mediated Wnt antagonism and that Kremen may only play a role when cells express a high level of LRP5/6...
  67. ncbi Severe hypercholesterolemia, impaired fat tolerance, and advanced atherosclerosis in mice lacking both low density lipoprotein receptor-related protein 5 and apolipoprotein E
    Kenta Magoori
    Tohoku University Gene Research Center, Aoba, Sendai 981 8555, Japan
    J Biol Chem 278:11331-6. 2003
    ..These data suggest that LRP5 mediates both apoE-dependent and apoE-independent catabolism of plasma lipoproteins...
  68. pmc Verification of predicted alternatively spliced Wnt genes reveals two new splice variants (CTNNB1 and LRP5) and altered Axin-1 expression during tumour progression
    Heike Pospisil
    Center for Bioinformatics, University of Hamburg, Bundesstrasse 43, 20146 Hamburg, Germany
    BMC Genomics 7:148. 2006
    ..For some of the Wnt pathway genes the existence of splice variants was either proposed (e.g. beta-Catenin and CTNNB1) or described only in non-colon tissues (e.g. GSK3beta) or hitherto not published (e.g. LRP5)...
  69. ncbi R-spondin1 synergizes with Wnt3A in inducing osteoblast differentiation and osteoprotegerin expression
    Wenyan Lu
    Department of Biochemistry and Molecular Biology, Drug Discovery Division, Southern Research Institute, Birmingham, AL 35255, USA
    FEBS Lett 582:643-50. 2008
    ..Finally, we demonstrated that Rspo1 synergized with Wnt3A to induce primary mouse osteoblast differentiation. Together, these findings suggest that Rpos1 may play an important role in bone remodeling...
  70. ncbi Seven novel sequence variants in the human low density lipoprotein receptor related protein 5 (LRP5) gene
    Minoru Okubo
    Department of Endocrinology and Metabolism, Okinaka Memorial Institute for Medical Research and Toranomon Hospital, Tokyo, Japan
    Hum Mutat 19:186. 2002
    ..To our knowledge, this is the first report in the literature of sequence variants in the human LRP5 gene...
  71. ncbi Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men
    E Grundberg
    Department of Medical Sciences, Uppsala University Hospital, 75185 Uppsala, Sweden
    Osteoporos Int 19:829-37. 2008
    ..Results showed an association of the Val667Met SNP with spine BMD in 3,800 young and elderly men...
  72. pmc Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling
    Shunfu Piao
    College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan, Korea
    PLoS ONE 3:e4046. 2008
    ..These observations demonstrate that phosphorylated LRP6/5 both recruits and directly inhibits GSK3beta using two distinct portions of its cytoplasmic sequence, and suggest a novel mechanism of activation in this signaling pathway...
  73. ncbi Hypomorphic expression of Dkk1 in the doubleridge mouse: dose dependence and compensatory interactions with Lrp6
    Bryan T MacDonald
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109 0618, USA
    Development 131:2543-52. 2004
    ..These compensatory interactions between Dkk1 and Lrp6 demonstrate the importance of correctly balancing positive and negative regulation of Wnt signaling during mammalian development...
  74. pmc Parathyroid hormone signaling through low-density lipoprotein-related protein 6
    Mei Wan
    Department of Pathology, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Genes Dev 22:2968-79. 2008
    ..Thus, LRP6 coreceptor is a key element of the PTH signaling that regulates osteoblast activity...
  75. ncbi Association of polymorphisms in low-density lipoprotein receptor-related protein 5 gene with bone mineral density in postmenopausal Chinese women
    Zhen Lin Zhang
    Center for Preventing and Treating Osteoporosis, Osteoporosis Research Unit, The Sixth People s Hospital, Shanghai Jiaotong University, Shanghai 200233, China
    Acta Pharmacol Sin 26:1111-6. 2005
    ..To investigate the possible association of Q89R, N740N and A1330V polymorphisms in low-density lipoprotein receptor-related protein 5 (LRP5) gene with bone mineral density (BMD) in postmenopausal Chinese women...
  76. ncbi LRP5 gene polymorphisms and idiopathic osteoporosis in men
    S L Ferrari
    Service of Bone Diseases, Department of Rehabilitation and Geriatrics, Geneva University Hospital, Geneva, Switzerland
    Bone 37:770-5. 2005
    ..In conclusion, these data indicate beyond a significant role for environmental factors, an association between LRP5 variants and idiopathic osteoporosis in males, pointing to a role of LRP5 in this disease...
  77. ncbi Molecular bases of the regulation of bone remodeling by the canonical Wnt signaling pathway
    Donald A Glass
    Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, 77030, USA
    Curr Top Dev Biol 73:43-84. 2006
    ....
  78. ncbi Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity
    Y Dong
    Pharmaceutical Division, Bayer Corporation, West Haven, Connecticut, 06516 4175, USA
    Biochem Biophys Res Commun 251:784-90. 1998
    ..We predict that LR3 is a multi-functional protein with potential mitogenic activity...
  79. ncbi The Wnt signaling receptor Lrp5 is required for mammary ductal stem cell activity and Wnt1-induced tumorigenesis
    Charlotta Lindvall
    Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
    J Biol Chem 281:35081-7. 2006
    ..These findings suggest that Lrp5-mediated canonical signaling is required for mammary ductal stem cell activity and for tumor development in response to oncogenic Wnt effectors...
  80. ncbi The low density lipoprotein receptor-related protein contributes to selective uptake of high density lipoprotein cholesteryl esters by SW872 liposarcoma cells and primary human adipocytes
    G Vassiliou
    Lipoprotein and Atherosclerosis Group, University of Ottawa Heart Institute, Ottawa, Ontario K1Y 4E9, Canada
    J Biol Chem 276:48823-30. 2001
    ..We discuss the possible mechanisms by which the endocytic receptor, LRP, can mediate selective uptake...
  81. pmc Phosphorylation of PPP(S/T)P motif of the free LRP6 intracellular domain is not required to activate the Wnt/beta-catenin pathway and attenuate GSK3beta activity
    Brandon Beagle
    Department of Anesthesiology, University of Rochester, Rochester, New York 14642, USA
    J Cell Biochem 108:886-95. 2009
    ....
  82. pmc Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men
    Douglas P Kiel
    Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, MA 02131, USA
    Bone 40:587-96. 2007
    ..These observations suggest that Wnt-LRP5 may play a role in the adaptation of bone to mechanical load in humans, and may explain some gender-related differences in bone mass...
  83. ncbi Calcium coordination and pH dependence of the calcium affinity of ligand-binding repeat CR7 from the LRP. Comparison with related domains from the LRP and the LDL receptor
    M Simonovic
    Department of Biochemistry and Molecular Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612-4316, USA
    Biochemistry 40:15127-34. 2001
    ....
  84. ncbi Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men
    Joyce B J van Meurs
    Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands
    J Bone Miner Res 21:141-50. 2006
    ..LRP5 variation was associated to both BMD and frame size, whereas both LRP5 and 6 variations were associated with an increased fracture risk in males...
  85. ncbi The A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) associates with low peak bone mass in young healthy men
    Anne Saarinen
    Folkhälsan Institute of Genetics and Department of Medical Genetics, University of Helsinki, Helsinki, Finland
    Bone 40:1006-12. 2007
    ..Whether this is due to influence on bone mass acquisition or on bone loss thereafter has not been established...
  86. ncbi Pathogenic mutations and polymorphisms in the lipoprotein receptor-related protein 5 reveal a new biological pathway for the control of bone mass
    Serge L Ferrari
    Division of Bone Diseases, Department of Rehabilitation and Geriatrics, Geneva University Hospital, Geneva, Switzerland
    Curr Opin Lipidol 16:207-14. 2005
    ..This review summarizes recent findings concerning the genomic variations of the lipoprotein receptor-related protein 5 (LPR5) in relation to bone biology...
  87. ncbi Decreased BMD and limb deformities in mice carrying mutations in both Lrp5 and Lrp6
    Sheri L Holmen
    Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan, USA
    J Bone Miner Res 19:2033-40. 2004
    ..We found that compound mutants had dose-dependent deficits in BMD and limb formation, suggesting functional redundancy between these two genes in bone and limb development...
  88. pmc Association between bone mineral density and LDL receptor-related protein 5 gene polymorphisms in young Korean men
    Jung Min Koh
    Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
    J Korean Med Sci 19:407-12. 2004
    ..Although we failed to demonstrate a clear association between the LRP5 polymorphism and peak bone mass in young men, the present study suggests that larger-scale studies on the Q89R polymorphism need to be performed...
  89. pmc Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6
    Joshua Wolf
    Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA
    FEBS Lett 582:255-61. 2008
    ..Instead, we show that each LRP6 PPPS/TP motif contributes in a combinatorial fashion to activate the canonical Wnt-beta-catenin pathway...
  90. ncbi LRP5 and Wnt signaling: a union made for bone
    Mark L Johnson
    Osteoporosis Research Center, Creighton University School of Medicine, Omaha, Nebraska 68131, USA
    J Bone Miner Res 19:1749-57. 2004
  91. pmc The internally truncated LRP5 receptor presents a therapeutic target in breast cancer
    Peyman Björklund
    Department of Surgical Sciences, Endocrine Unit, Uppsala University, Uppsala University Hospital, Uppsala, Sweden
    PLoS ONE 4:e4243. 2009
    ....
  92. ncbi The genetics of low-density lipoprotein receptor-related protein 5 in bone: a story of extremes
    Wendy Balemans
    Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, B 2610 Antwerp, Belgium
    Endocrinology 148:2622-9. 2007
    ..This review focuses on the genetics of LRP5 and summarizes the findings on monogenic bone conditions as well as the current knowledge of its involvement in the pathogenesis of osteoporosis...
  93. pmc Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis
    Joyce B J van Meurs
    Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
    JAMA 299:1277-90. 2008
    ..Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene cause rare syndromes characterized by altered bone mineral density (BMD). More common LRP5 variants may affect osteoporosis risk in the general population...
  94. ncbi Contribution of the LRP5 gene to normal variation in peak BMD in women
    Daniel L Koller
    Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA
    J Bone Miner Res 20:75-80. 2005
    ..Association between SNPs in LRP5 and hip and spine BMD was measured in 1301 premenopausal women. Only a small proportion of the BMD variation was attributable to LRP5 in our sample...
  95. ncbi High bone mass in mice expressing a mutant LRP5 gene
    Philip Babij
    Genomics, Wyeth Research, Andover, Massachusetts, USA
    J Bone Miner Res 18:960-74. 2003
    ..Together, these findings establish the importance of this novel and unexpected role of a lipoprotein receptor in regulating bone mass and afford a new model to explore LRP5 and its recent association with Wnt signaling in bone biology...
  96. ncbi Association of a single-nucleotide variation (A1330V) in the low-density lipoprotein receptor-related protein 5 gene (LRP5) with bone mineral density in adult Japanese women
    Yoichi Ezura
    Department of Molecular Biology, Institute of Gerontology, Nippon Medical School, 1 396, Kosugi cho, Nakahara ku, Kawasaki 211 8533, Japan
    Bone 40:997-1005. 2007
    ..Our results indicate that genetic variations in LRP5 are important factors affecting BMD in adult women and that 1330 V may contribute to osteoporosis susceptibility, at least in Japanese...
  97. ncbi LRP5 gene polymorphisms predict bone mass and incident fractures in elderly Australian women
    J Bollerslev
    School of Medicine and Pharmacology, University of Western Australia, Nedlands
    Bone 36:599-606. 2005
    ..67 [1.02-2.78], P = 0.045), indicating factors other than bone mass are of importance for bone strength. In conclusion, genetic variation in LRP5 seems to be of importance for regulation of bone mass and osteoporotic fractures...
  98. pmc Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study
    J B Richards
    Department of Twin Research and Genetic Epidemiology, King s College London, London, UK
    Lancet 371:1505-12. 2008
    ..Osteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density...
  99. ncbi The role of the Wnt signaling pathway in osteoblast commitment and differentiation
    Maria P Yavropoulou
    Department of Endocrinology and Metabolism, Aristotle University of Thessaloniki, AHEPA University Hospital, Thessaloniki, Greece
    Hormones (Athens) 6:279-94. 2007
    ..We also outlined a probable working integrating model of the mechanism of bone formation...
  100. ncbi Very low density lipoprotein receptor, a negative regulator of the wnt signaling pathway and choroidal neovascularization
    Ying Chen
    Department of Cell Biology, University of Oklahoma Health Sciences Center, 941 Stanton L Young Boulevard, Oklahoma City, OK 73104, USA
    J Biol Chem 282:34420-8. 2007
    ..These results suggest that VLDLR functions as a negative regulator of CNV, and this function is mediated through the wnt pathway...
  101. ncbi In vivo analysis of Wnt signaling in bone
    Donald A Glass
    Medical Scientist Training Prtogram, Baylor College of Medicine, Houston, TX 77030, USA
    Endocrinology 148:2630-4. 2007
    ..These mouse models help establish the canonical Wnt signaling pathway as a major regulator of chondrogenesis, osteoblastogenesis, and osteoclastogenesis. This review will summarize these advances...

Research Grants34

  1. Osteoblastogenesis in Aortic Valve Calcification
    Nalini Rajamannan; Fiscal Year: 2006
    ..If hypercholesterolemia stimulates the development of calcification in the aortic valve then the use of medical therapy such as HMG CoA reductase medications may have a role in the medical therapy of calcific aortic stenosis. ..
  2. Molecular basis of Wnt receptor interactions
    William I Weis; Fiscal Year: 2013
    ..Structural studies will be performed on Drosophila WntD to define surfaces in the homologous classical Wnts important for receptor binding. ..
  3. Molecular basis of Wnt receptor interactions
    William I Weis; Fiscal Year: 2010
    ..This proposal aims to understand the interactions of Wnts and their receptors. The molecular information from these studies could provide a foundation for rational, efficient development of agents that act on cancer stem cells. ..
  4. METABOLISM OF THE VLDL RECEPTOR AND APOE RECEPTOR 2
    Joachim Herz; Fiscal Year: 2009
    ..This may provide novel targets for rational drug design and treatment of atherosclerosis as well as of AD, both disorders of increasing medical and socio-economic importance. ..
  5. APO E Receptors and Modulation of Fast Axonal Transport
    Joachim Herz; Fiscal Year: 2006
    ....
  6. GENETIC EPIDEMIOLOGY OF ALZHEIMERS DISEASE IN HISPANICS
    Richard Mayeux; Fiscal Year: 2003
    ..The ultimate goal of this project is to chromosomally localize genes that may increase the risk of AD among the Caribbean Hispanic ethnic group. ..
  7. Molecular Pathobiology of LRP1B Tumor Suppressor
    Guojun Bu; Fiscal Year: 2008
    ..abstract_text> ..
  8. EPIDEMIOLOGY OF DEMENTIA IN AN URBAN COMMUNITY
    Richard Mayeux; Fiscal Year: 2008
    ..The overall theme of this fourth renewal application is to identify reliable and valid antecedent biomarkers of AD and MCI and to extend these and other clinical parameters to the measurement of disease progression. ..
  9. NEW WAYS TO FIND HUMAN BMD GENES USING MOUSE QTL MAPPING
    David Karasik; Fiscal Year: 2008
    ..This integrated bioinformatic approach ultimately can be extended to gene identification for other complex diseases. [unreadable] [unreadable] [unreadable]..
  10. GENETIC CONTROL OF CELL FATE DIVERSITY IN DROSOPHILA
    Amy Bejsovec; Fiscal Year: 2003
    ..This specificity may indicate a novel function in the Wg pathway. Aim 4 describes a plan for the molecular cloning of this new gene and for the subsequent characterization of its gene product. ..
  11. LRP AND APP PROCESSING IN NEURODEGENERATION
    Guojun Bu; Fiscal Year: 2009
    ..Because apoE is a major risk factor for Alzheimer's disease, a leading cause of dementia in elderly, our results may provide knowledge for diagnosis and/or therapy for Alzheimer's disease. ..
  12. Molecular Function of Chemoattractant-Mediated Signaling
    Dianqing Wu; Fiscal Year: 2009
    ..This mechanism should also regulate cell motility, because continuous formation of F actin at the leading edge provides a primary driving force for leukocyte locomotion. ..
  13. WNT SIGNALING AND BONE BIOLOGY
    Dianqing Wu; Fiscal Year: 2009
    ..Importantly, they increase osteogenesis in culture models. In this proposal, we will identify more efficient compounds and also carry out tests using in vivo models. ..
  14. THE FUNCTION OF NEUROTRANSMITTERS IN BONE BIOLOGY
    MATTHEW BLIZIOTES; Fiscal Year: 2009
    ..This research should contribute to new treatment and prevention regimens for osteoporosis and thus have a significant positive impact on the health care of the aging population. ..
  15. RAP AS A MOLECULAR CHAPERONE/ESCORT PROTEIN FOR LRP
    Guojun Bu; Fiscal Year: 2002
    ....
  16. Protein S: Neurovascular Protection in Stroke
    Berislav V Zlokovic; Fiscal Year: 2010
    ..B. Berk (Rochester) (Tyro 3 RTK-Akt signaling) and Dr. M. Chopp (Henry Ford) (rat stroke model). The results will provide mechanistic insights and test therapeutic agents that may be translated to improved therapy for ischemic stroke. ..
  17. Unraveling Musculoskeletal Pleiotropy Using Genome-Wide Association
    David Karasik; Fiscal Year: 2010
    ..The above will improve substantially quality of life and decrease health care costs for millions of middle-aged and elderly Americans. ..
  18. Genome-wide ENU mutagenesis screen for Runx2 modifiers
    Patricia Ducy; Fiscal Year: 2006
    ..abstract_text> ..
  19. GENETIC OF BONE STRUCTURAL GEOMETRY: FRAMINGHAM COHORTS
    David Karasik; Fiscal Year: 2006
    ..Linkage analysis will also be combined with family based tests of association with candidate genes that lie under the peak, with additional mapping with single nucleotide polyrnorphisms. ..
  20. GENETIC EPIDEMIOLOGY OF AGING IN A MULTIETHNIC COMMUNITY
    Richard Mayeux; Fiscal Year: 2002
    ....
  21. AGING BRAIN--CEREBROVASCULAR MECHANISM & AMYLOID BETA
    Berislav Zlokovic; Fiscal Year: 2003
    ..abstract_text> ..
  22. REGULATION OF CBFA1 EXPRESSION
    Patricia Ducy; Fiscal Year: 2003
    ..2-kb Cbfa1 proximal promoter and of the cis-acting elements it contains in transgenic mice. - To identify other cell-specific enhancer elements located outside the 2.2.-kb proximal Cbfa1 promoter. ..
  23. Molecular Function of Chemoattractant-Mediated Signaling
    Dianqing Wu; Fiscal Year: 2004
    ....
  24. Alzheimer's ABeta, Apolipoproteins & Blood-Brain Barrier
    Berislav Zlokovic; Fiscal Year: 2004
    ....
  25. TWO X-LINKED GENES THAT REGULATE MINERAL HOMEOSTASIS
    Michael Whyte; Fiscal Year: 2002
    ....
  26. Trochanteric Padding to Prevent Hip Fractures
    Douglas Kiel; Fiscal Year: 2005
    ..This will be the largest clinical trial of this biomechanically tested, energy absorbing and distributing hip protector ever conducted in the United States. ..
  27. OSTEOGENIC MECHANICAL STIMULI-PREVENT/REVERSE BONE LOSS
    Douglas Kiel; Fiscal Year: 2002
    ..We anticipate that the results of this study will demonstrate the attributes of a unique osteogenic biomechanical therapy for osteoporosis. ..
  28. The Genetic Etiology of Patent Ductus Arteriosus
    Arya Mani; Fiscal Year: 2006
    ..Lifton' s laboratory provide an ideal environment for acquiring the vestigative skills needed to launch my research career. This award provides the essential components to develop career and will maximize my academic potential. ..
  29. Cytoskeletal Modulation of Bone Cell Mechanosensitivity
    ALEXANDER ROBLING; Fiscal Year: 2006
    ..Insights into the mechanisms of mechanosensory loss and recovery hold potential in the public health arena for optimizing the positive effects of loading on bone mass, fragility, and fracture risk. ..
  30. The biochemical mechanism of Wnt signaling
    BERNADETTE HOLDENER; Fiscal Year: 2007
    ..abstract_text> ..
  31. Carrier Mediated Uptake of ABeta In Vivo & In Vitro
    MARNI HARRIS WHITE; Fiscal Year: 2007
    ..Understanding this mechanism may help to resolve the paradox that "Abeta plaque deposition is not sufficient to cause Alzheimer's" and could lead to new and better targets of intervention in Alzheimer's disease. ..
  32. NEUROTROPHIN REGULATION OF LRP IN CNS NEURONS
    Guojun Bu; Fiscal Year: 2001
    ....
  33. SIGNALING MECHANISMS FOR WNT PROTEINS
    Dianqing Wu; Fiscal Year: 2005
    ..3) To identify upstream regulators for Dvl using the affinity chromatographic and yeast two-hybrid approaches. ..