osteitis deformans

Summary

Summary: A disease marked by repeated episodes of increased bone resorption followed by excessive attempts at repair, resulting in weakened, deformed bones of increased mass. The resultant architecture of the bone assumes a mosaic pattern in which the fibers take on a haphazard pattern instead of the normal parallel symmetry.

Top Publications

  1. ncbi Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein
    Giles D J Watts
    Division of Genetics, Children s Hospital Boston, 300 Longwood Avenue, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 36:377-81. 2004
  2. pmc Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease
    Jeong Sun Ju
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Cell Biol 187:875-88. 2009
  3. pmc TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97
    Gillian P Ritson
    Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 30:7729-39. 2010
  4. ncbi Enhanced ATPase activities as a primary defect of mutant valosin-containing proteins that cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
    Atsushi Manno
    Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, Kyoto 606 8501, Japan
    Genes Cells 15:911-22. 2010
  5. ncbi Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F-fluoride positron emission tomography
    G J R Cook
    Department of Nuclear Medicine, Royal Marsden Hospital, Sutton, Surrey, United Kingdom
    J Bone Miner Res 17:854-9. 2002
  6. ncbi SQSTM1 gene analysis and gene-environment interaction in Paget's disease of bone
    Luigi Gennari
    Department of Internal Medicine, Endocrine Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy
    J Bone Miner Res 25:1375-84. 2010
  7. pmc Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts
    Jouni Vesa
    Department of Pediatrics, Division of Genetics and Metabolism, University of California, Irvine, CA 92868, USA
    Neuromuscul Disord 19:766-72. 2009
  8. ncbi The multiple faces of valosin-containing protein-associated diseases: inclusion body myopathy with Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis
    Angele Nalbandian
    Department of Pediatrics, Division of Genetics and Metabolism, 2501 Hewitt Hall, University of California Irvine, 2501 Hewitt Hall, Irvine, CA 92696, USA
    J Mol Neurosci 45:522-31. 2011
  9. ncbi Loss of ubiquitin-binding associated with Paget's disease of bone p62 (SQSTM1) mutations
    James R Cavey
    School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom
    J Bone Miner Res 20:619-24. 2005
  10. ncbi Founder effect in different European countries for the recurrent P392L SQSTM1 mutation in Paget's Disease of Bone
    Pui Yan Jenny Chung
    Department of Medical Genetics, University and University Hospital of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium
    Calcif Tissue Int 83:34-42. 2008

Detail Information

Publications230 found, 100 shown here

  1. ncbi Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein
    Giles D J Watts
    Division of Genetics, Children s Hospital Boston, 300 Longwood Avenue, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nat Genet 36:377-81. 2004
    ..Identification of VCP as causing IBMPFD has important implications for other inclusion-body diseases, including myopathies, dementias and Paget disease of bone (PDB), as it may define a new common pathological ubiquitin-based pathway...
  2. pmc Valosin-containing protein (VCP) is required for autophagy and is disrupted in VCP disease
    Jeong Sun Ju
    Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Cell Biol 187:875-88. 2009
    ..These data implicate VCP in autophagy and suggest that impaired autophagy explains the pathology seen in IBMPFD muscle, including TDP-43 accumulation...
  3. pmc TDP-43 mediates degeneration in a novel Drosophila model of disease caused by mutations in VCP/p97
    Gillian P Ritson
    Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Neurosci 30:7729-39. 2010
    ..We suggest that these findings are likely relevant to the pathogenic mechanism of a broad array of TDP-43 proteinopathies, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis...
  4. ncbi Enhanced ATPase activities as a primary defect of mutant valosin-containing proteins that cause inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
    Atsushi Manno
    Laboratory of Functional Biology, Kyoto University Graduate School of Biostudies, Kyoto 606 8501, Japan
    Genes Cells 15:911-22. 2010
    ..Elevated ATPase activities, thus, may be a hidden primary defect causing IBMPFD pathological phenotypes, which would be revealed when abnormal proteins are accumulated, as typically observed in aging...
  5. ncbi Quantification of skeletal kinetic indices in Paget's disease using dynamic 18F-fluoride positron emission tomography
    G J R Cook
    Department of Nuclear Medicine, Royal Marsden Hospital, Sutton, Surrey, United Kingdom
    J Bone Miner Res 17:854-9. 2002
    ....
  6. ncbi SQSTM1 gene analysis and gene-environment interaction in Paget's disease of bone
    Luigi Gennari
    Department of Internal Medicine, Endocrine Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy
    J Bone Miner Res 25:1375-84. 2010
    ..84 +/- 2.5 versus 2.76 +/- 2.2, p < .05). Overall, these data suggest that animal-related factors may be important in the etiology of PDB and may interact with SQSTM1 mutations in influencing disease severity...
  7. pmc Valosin containing protein associated inclusion body myopathy: abnormal vacuolization, autophagy and cell fusion in myoblasts
    Jouni Vesa
    Department of Pediatrics, Division of Genetics and Metabolism, University of California, Irvine, CA 92868, USA
    Neuromuscul Disord 19:766-72. 2009
    ....
  8. ncbi The multiple faces of valosin-containing protein-associated diseases: inclusion body myopathy with Paget's disease of bone, frontotemporal dementia, and amyotrophic lateral sclerosis
    Angele Nalbandian
    Department of Pediatrics, Division of Genetics and Metabolism, 2501 Hewitt Hall, University of California Irvine, 2501 Hewitt Hall, Irvine, CA 92696, USA
    J Mol Neurosci 45:522-31. 2011
    ..In this review, we will explore the pathogenesis and clinical phenotype of IBMPFD caused by VCP mutations...
  9. ncbi Loss of ubiquitin-binding associated with Paget's disease of bone p62 (SQSTM1) mutations
    James R Cavey
    School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom
    J Bone Miner Res 20:619-24. 2005
    ..This suggests that SQSTM1 mutations predispose to PDB through a common mechanism that depends on loss of ubiquitin-binding by p62...
  10. ncbi Founder effect in different European countries for the recurrent P392L SQSTM1 mutation in Paget's Disease of Bone
    Pui Yan Jenny Chung
    Department of Medical Genetics, University and University Hospital of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Belgium
    Calcif Tissue Int 83:34-42. 2008
    ..The chance to obtain this result due to 33 independent mutation events is 3.97 x 10(-14), providing strong evidence for a founder effect of the P392L SQSTM1 mutation in Belgian, Dutch, and Spanish patients with PDB...
  11. ncbi Ubiquitin recognition by the ubiquitin-associated domain of p62 involves a novel conformational switch
    Jed Long
    School of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom
    J Biol Chem 283:5427-40. 2008
    ..The conformational switch observed on binding may represent a novel mechanism that underlies specificity in regulating signalinduced protein recognition events...
  12. pmc Imbalances in p97 co-factor interactions in human proteinopathy
    Vanesa Fernández-Sáiz
    Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
    EMBO Rep 11:479-85. 2010
    ..Our results suggest that imbalanced co-factor binding to p97 is a key pathological feature of IBMPFD and potentially of other proteinopathies involving p97...
  13. ncbi TDP-43 in the ubiquitin pathology of frontotemporal dementia with VCP gene mutations
    Manuela Neumann
    Center for Neuropathology and Prion Research, Ludwig Maximilians University, Munich, Germany
    J Neuropathol Exp Neurol 66:152-7. 2007
    ..TDP-43 is a common pathologic substrate linking a variety of distinct patterns of FTLD-U pathology caused by different genetic alterations...
  14. pmc Evidence for a novel osteosarcoma tumor-suppressor gene in the chromosome 18 region genetically linked with Paget disease of bone
    M J Nellissery
    Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA
    Am J Hum Genet 63:817-24. 1998
    Paget disease of bone, or "osteitis deformans," is a bone disorder characterized by rapid bone remodeling resulting in abnormal bone formation...
  15. ncbi A novel mutation (K378X) in the sequestosome 1 gene associated with increased NF-kappaB signaling and Paget's disease of bone with a severe phenotype
    Sarah L Rea
    Laboratory for Molecular Endocrinology, Western Australian Institute for Medical Research, University of Western Australia, Nedlands
    J Bone Miner Res 21:1136-45. 2006
    ..p62 mutants increased NF-kappaB activation and significantly potentiated osteoclast formation and bone resorption in human primary cell cultures...
  16. ncbi Paget disease of bone
    Tim Cundy
    Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
    Trends Endocrinol Metab 19:246-53. 2008
    ..Most observations seem to fit best with the idea that Paget disease behaves as a multifocal benign neoplasm...
  17. pmc Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone
    Omar M E Albagha
    Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
    Nat Genet 42:520-4. 2010
    ..09 x 10(-13)) and with rs3018362 on 18q21 near the TNFRSF11A gene (P = 5.27 x 10(-13)). These studies provide new insights into the pathogenesis of PDB and identify OPTN, CSF1 and TNFRSF11A as candidate genes for disease susceptibility...
  18. ncbi Differential gene expression in cultured osteoblasts and bone marrow stromal cells from patients with Paget's disease of bone
    Dorit Naot
    Department of Medicine, University of Auckland, New Zealand
    J Bone Miner Res 22:298-309. 2007
    ..We identified several differentially regulated genes, and we suggest that these changes could lead to the formation of the lesions...
  19. ncbi Detection of canine distemper virus in 100% of Paget's disease samples by in situ-reverse transcriptase-polymerase chain reaction
    A P Mee
    Bone Disease Research Centre, University Department of Medicine, Manchester Royal Infirmary, UK
    Bone 23:171-5. 1998
    ..These results provide additional proof that CDV is present within pagetic bone and further support the hypothesis that paramyxoviruses are involved in the etiopathology of Paget's disease...
  20. ncbi Clinical delineation and localization to chromosome 9p13.3-p12 of a unique dominant disorder in four families: hereditary inclusion body myopathy, Paget disease of bone, and frontotemporal dementia
    M J Kovach
    Division of Genetics and Metabolism, Department of Pediatrics, Southern Illinois University School of Medicine, Springfield, Illinois, USA
    Mol Genet Metab 74:458-75. 2001
    ..Hence, autosomal dominant inclusion body myopathy (HIBM), Paget disease of bone (PDB), and frontotemporal dementia (FTD) localizes to a 1.08-6.46 cM critical interval on 9p13.3-12 in the region of autosomal recessive IBM2...
  21. ncbi Guidelines on the management of Paget's disease of bone
    P L Selby
    Department of Medicine, Manchester Royal Infirmary, Manchester, UK
    Bone 31:366-73. 2002
  22. ncbi New knowledge on critical osteoclast formation and activation pathways from study of rare genetic diseases of osteoclasts: focus on the RANK/RANKL axis
    J C Crockett
    Bone and Musculoskeletal Research Programme, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, AB25 2ZD, Aberdeen, UK
    Osteoporos Int 22:1-20. 2011
    ..We highlight areas that require further study, particularly in light of the pharmacological interest in targeting the RANK signalling pathway to treat diseases caused by excessive bone resorption...
  23. ncbi Paget's disease of bone in The Netherlands: a population-based radiological and biochemical survey--the Rotterdam Study
    Marelise E M W Eekhoff
    Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
    J Bone Miner Res 19:566-70. 2004
    ..Subjects with raised and normal ALP from a population cohort were matched (1 in 6, total 548), and radiographs were taken. ALP was an excellent marker of the disease (RR, 10.9), but the majority of those affected had normal ALP...
  24. ncbi Three novel mutations in SQSTM1 identified in familial Paget's disease of bone
    Teresa L Johnson-Pais
    Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas 78229, USA
    J Bone Miner Res 18:1748-53. 2003
    ..Disruptions of the C-terminal domain of SQSTM1 seem to be a leading cause of familial PDB...
  25. ncbi Epidemiological, clinical, and genetic characteristics of Paget's disease of bone in a rural area of Calabria, Southern Italy
    D Rendina
    Department of Clinical and Experimental Medicine, Federico II University Medical School, Via S Pansini, 5 80131 Naples, Italy
    J Endocrinol Invest 33:519-25. 2010
    ..The prevalence of Paget's disease of bone (PDB) is unknown in peninsular Southern Italy, although an elevated clinical severity of the disease was reported in patients from Campania...
  26. ncbi Sequestosome 1 mutations in Paget's disease of bone in Australia: prevalence, genotype/phenotype correlation, and a novel non-UBA domain mutation (P364S) associated with increased NF-kappaB signaling without loss of ubiquitin binding
    Sarah L Rea
    Laboratory for Molecular Endocrinology, Western Australian Institute for Medical Research and UWA Centre for Medical Research, University of Western Australia, Nedlands, Australia
    J Bone Miner Res 24:1216-23. 2009
    ..This suggests that increased NF-kappaB signaling, but not the impairment of ubiquitin binding, may be essential in the pathogenesis of PDB associated with SQSTM1 mutations...
  27. ncbi Genetic epidemiology of Paget's disease of bone in italy: sequestosome1/p62 gene mutational test and haplotype analysis at 5q35 in a large representative series of sporadic and familial Italian cases of Paget's disease of bone
    Alberto Falchetti
    Department of Internal Medicine, University of Florence, Florence, Italy
    Calcif Tissue Int 84:20-37. 2009
    ..This may be helpful in estimating the true rate of de novo mutations. We confirm the data on the existence of both a mutational hotspot at the UBA domain of SQSTM1/p62 and a founder effect in the PDB population...
  28. ncbi Novel UBA domain mutations of SQSTM1 in Paget's disease of bone: genotype phenotype correlation, functional analysis, and structural consequences
    Lynne J Hocking
    Department of Medicine and Therapeutics, University of Aberdeen, Aberdeen, United Kingdom
    J Bone Miner Res 19:1122-7. 2004
    ..Functional and structural analysis showed that disease severity was related to the type of mutation but was unrelated to the polyubiquitin-binding properties of the mutant UBA domain peptides...
  29. ncbi Late-onset autosomal dominant limb girdle muscular dystrophy and Paget's disease of bone unlinked to the VCP gene locus
    Michael Kottlors
    Division of Neuropediatrics and Muscle Disorders, University Children s Hospital Freiburg, Freiburg, Germany
    J Neurol Sci 291:79-85. 2010
    ..The family presented here suggests that a yet-unknown genetic defect can give rise to an autosomal dominant myopathy with Paget's disease but without dementia...
  30. ncbi Common susceptibility alleles and SQSTM1 mutations predict disease extent and severity in a multinational study of patients with Paget's disease
    Omar M E Albagha
    Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
    J Bone Miner Res 28:2338-46. 2013
    ..It is possible that with further refinement, genetic profiling may be of clinical value in identifying individuals at high risk of severe disease who might benefit from enhanced surveillance and early intervention...
  31. ncbi Delayed development of Paget's disease in offspring inheriting SQSTM1 mutations
    Mark J Bolland
    Department of Medicine, University of Auckland, New Zealand
    J Bone Miner Res 22:411-5. 2007
    ..At any given age, the offspring were less likely to be diagnosed with Paget's disease and had less severe disease than their parents...
  32. ncbi Identification and molecular characterization of a novel splice-site mutation (G1205C) in the SQSTM1 gene causing Paget's disease of bone in an extended American family
    G Beyens
    Department of Medical Genetics, University and University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Antwerp, Belgium
    Calcif Tissue Int 79:281-8. 2006
    ..PDB mutations that disrupt the function of the PEST domain of SQSTM1 have not been reported before, so probably the pathogenic effect of both transcripts resides in the disruption of the ubiquitin-binding properties of the protein...
  33. ncbi Indications for a genetic association of a VCP polymorphism with the pathogenesis of sporadic Paget's disease of bone, but not for TNFSF11 (RANKL) and IL-6 polymorphisms
    Pui Yan Jenny Chung
    Department of Medical Genetics, University of Antwerp, Antwerp, 2610, Belgium
    Mol Genet Metab 103:287-92. 2011
    ..e. TNFRSF11A, CSF1, OPTN and TM7SF4), independent effect of each gene region was found and the cumulative population attributable risk is 72.7%...
  34. pmc A progressive translational mouse model of human valosin-containing protein disease: the VCP(R155H/+) mouse
    Angele Nalbandian
    Department of Pediatrics, Division of Genetics and Metabolism, 2501 Hewitt Hall, University of California, Irvine, Irvine, California 92696, USA
    Muscle Nerve 47:260-70. 2013
    ..More recently, these mutations have been linked to 2% of familial amyotrophic lateral sclerosis (ALS) cases. A knock-in mouse model offers the opportunity to study VCP-associated pathogenesis...
  35. ncbi Domain-specific mutations in sequestosome 1 (SQSTM1) cause familial and sporadic Paget's disease
    Lynne J Hocking
    Department of Medicine and Therapeutics, University of Aberdeen, UK
    Hum Mol Genet 11:2735-9. 2002
    ..0001). These studies confirm that mutations affecting the ubiquitin-binding domain of SQSTM1 are a common cause of familial and sporadic Paget's disease of bone...
  36. ncbi The ivory vertebra sign
    Travis S Graham
    Department of Radiology, University of Colorado Health Sciences Center, 4200 E Ninth Ave, Denver, CO 80262 USA
    Radiology 235:614-5. 2005
  37. ncbi Proteomic analysis of a drosophila IBMPFD model reveals potential pathogenic mechanisms
    Hsin Tzu Chan
    Institute of Bioinformatics and Structural Biology and Department of Medical Sciences, National Tsing Hua University, Hsinchu, Taiwan
    Mol Biosyst 8:1730-41. 2012
    ..The molecular analysis of IBMPFD disease may benefit from the proteomics approach which combines the advantages of high throughput analysis and the focus on protein levels...
  38. ncbi The S349T mutation of SQSTM1 links Keap1/Nrf2 signalling to Paget's disease of bone
    Tao Wright
    School of Biomedical Sciences, University of Nottingham, UK
    Bone 52:699-706. 2013
    ..Thus, SQSTM1-mediated dysregulation of the Keap1-Nrf2 axis, which could potentially lead to aberrant production of oxidative response genes, may contribute to disease aetiology in a subset of PDB patients...
  39. ncbi Osteitis deformans (Paget's disease) in a Burmese python (Python molurus bivittatus)--a case report
    Rosario Preziosi
    Department of Veterinary Public Health and Animal Pathology, Alma Mater Studiorum, Universita di Bologna, Via Tolara di Sopra 50, I 40064 Ozzano Emilia BO, Italy
    Vet J 174:669-72. 2007
    b>Osteitis deformans (Paget's disease of bone) is a chronic focal disorder of bone remodelling characterized by an initial increase in osteoclast-mediated bone resorption, with subsequent compensatory increase in new bone formation, ..
  40. ncbi Epidemiology of Paget's disease of bone: a systematic review and meta-analysis of secular changes
    Luis Corral-Gudino
    Servicio de Medicina Interna, Hospital El Bierzo, Ponferrada, Leon, Spain
    Bone 55:347-52. 2013
    ..Several studies have suggested that the prevalence and severity of PDB have fallen in recent years. The magnitude of this trend and its globalization have not been well established...
  41. ncbi A randomized clinical trial comparing oral alendronate and intravenous pamidronate for the treatment of Paget's disease of bone
    J P Walsh
    Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia
    Bone 34:747-54. 2004
    ..In patients previously treated with pamidronate, alendronate is more effective...
  42. ncbi Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations
    E W M Eekhoff
    Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Arthritis Rheum 50:1650-4. 2004
    ..To estimate the occurrence of familial Paget's disease of bone in The Netherlands, to examine the prevalence of mutations of the sequestosome 1 gene (SQSTM1) in identified families, and to assess potential genotype-phenotype associations...
  43. ncbi Genetics of Paget's disease of bone
    Anna Daroszewska
    Institute of Medical Sciences, University of Aberdeen Medical School, Aberdeen AB25 2ZD, UK
    Clin Sci (Lond) 109:257-63. 2005
    ....
  44. ncbi Mutations of SQSTM1 are associated with severity and clinical outcome in paget disease of bone
    Micaela Rios Visconti
    Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
    J Bone Miner Res 25:2368-73. 2010
    ....
  45. ncbi Novel VCP mutations in inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
    G D J Watts
    Division of Genetics, Children s Hospital Boston, Harvard Medical School, Boston, MA, USA
    Clin Genet 72:420-6. 2007
    ..These new mutations may cause structural changes in VCP and provide some insight into the functional effects of pathogenic mutations...
  46. ncbi Management of Paget's disease of bone
    A L Langston
    Health Services Research Unit, University of Aberdeen, UK
    Rheumatology (Oxford) 43:955-9. 2004
    ....
  47. ncbi Paget's disease of bone: evidence for a susceptibility locus on chromosome 18q and for genetic heterogeneity
    S I Haslam
    Department of Medicine and Therapeutics, University of Aberdeen, United Kingdom
    J Bone Miner Res 13:911-7. 1998
    ..Data from three families did not support evidence of linkage to 18q21-22 however, indicating that Paget's disease is genetically heterogeneous and suggests the presence of at least one additional locus which remains to be discovered...
  48. ncbi Clinical and molecular studies in a unique family with autosomal dominant limb-girdle muscular dystrophy and Paget disease of bone
    V E Kimonis
    Department of Pediatircs, Southern Illinois University School of Medicine, Springfield 62794 9658, USA
    Genet Med 2:232-41. 2000
    ..To characterize the clinical features and perform linkage analysis of candidate loci in a large Illinois family with autosomal dominant limb-girdle muscular dystrophy (LGMD) and Paget disease of bone (PDB)...
  49. ncbi Inclusion body myopathy with Paget disease of bone and frontotemporal dementia linked to VCP p.Arg155Cys in a Korean family
    Eun Joo Kim
    Department of Neurology, Pusan National University Hospital, Pusan National University School of Medicine and Medical Research Institute, Busan, Korea
    Arch Neurol 68:787-96. 2011
    ..Missense mutations in the valosin-containing protein (VCP) gene on chromosome 9p13.3-p12 cause inclusion body myopathy with Paget disease of bone and frontotemporal dementia (hereafter referred to as IBMPFD; OMIM 167320)...
  50. ncbi Genetics of bone diseases: Paget's disease, fibrous dysplasia, osteopetrosis, and osteogenesis imperfecta
    Laetitia Michou
    Service de rhumatologie du CHUQ CHUL H1365, Departement de Medecine, Centre de Recherche du CHUQ CHUL, Universite Laval, 2705, boulevard Laurier, G1V 4G2, Quebec, Canada
    Joint Bone Spine 78:252-8. 2011
    ..The recent identification of mutations in the CRTAP, LEPRE1, and PPIB genes in recessive forms has radically changed the classification of osteogenesis imperfecta and generated new pathophysiological hypotheses...
  51. ncbi Clinical and genetic heterogeneity in chromosome 9p associated hereditary inclusion body myopathy: exclusion of GNE and three other candidate genes
    Giles D J Watts
    Division of Genetics and Metabolism, Children s Hospital, Harvard Medical School, 300 Longwood Avenue, Fegan 5, Boston, MA 02115, USA
    Neuromuscul Disord 13:559-67. 2003
    ..Expression studies indicate that GNE has a tissue-specific splice pattern, with four splice variants. Mutation analysis in three other candidate genes (beta-tropomyosin, NDUFB6 and SMU1) did not identify any mutations...
  52. ncbi Two Australian families with inclusion-body myopathy, Paget's disease of bone and frontotemporal dementia: novel clinical and genetic findings
    Kishore R Kumar
    Department of Neurology, Royal North Shore Hospital, St Leonards, NSW 2065, Australia
    Neuromuscul Disord 20:330-4. 2010
    ..Leu198Trp). Our findings broaden the phenotypic spectrum of IBMPFD and further emphasise the resemblance to amyotrophic lateral sclerosis in some cases...
  53. ncbi Valosin-containing protein and the pathogenesis of frontotemporal dementia associated with inclusion body myopathy
    Jake B Guinto
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 422 Curie Blvd, 605B Stellar Chance Building, Philadelphia, PA, 19104 6140, USA
    Acta Neuropathol 114:55-61. 2007
    ..In this report, we review current literature on IBMPFD, focusing on the pathology of the disease and the biology of VCP with respect to IBMPFD...
  54. ncbi Impact of p62/SQSTM1 UBA domain mutations linked to Paget's disease of bone on ubiquitin recognition
    Thomas P Garner
    Centre for Biomolecular Sciences, School of Chemistry, University Park, University of Nottingham, Nottingham, U K
    Biochemistry 50:4665-74. 2011
    ....
  55. ncbi A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia
    R D Fanganiello
    Centro de Estudos do Genoma Humano, Departamento de Genética e Biologia Evolutiva, Instituto de Biociencias, Universidade de Sao Paulo, SP, Brasil
    Braz J Med Biol Res 44:374-80. 2011
    ..Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad...
  56. ncbi Characteristics and familial aggregation of Paget's disease of bone in Italy
    Daniela Merlotti
    Department of Internal Medicine, Endocrine Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy
    J Bone Miner Res 20:1356-64. 2005
    ..Familial aggregation was observed in 15% of cases...
  57. ncbi Randomized, active-controlled study of once-weekly alendronate 280 mg high dose oral buffered solution for treatment of Paget's disease
    M Hooper
    University of Sydney, 56 St Johns Ave, Gordon, NSW, 2072, Australia
    Osteoporos Int 20:141-50. 2009
    ..A once-weekly alendronate 280 mg oral buffered solution was compared with an alendronate 40 mg/day tablet. While both were similarly effective, the tablet appeared to be better tolerated in this study...
  58. ncbi Multicenter blinded analysis of RT-PCR detection methods for paramyxoviruses in relation to Paget's disease of bone
    Stuart H Ralston
    Rheumatic Diseases Unit, School of Molecular and Clinical Medicine, University of Edinburgh, Edinburgh, UK
    J Bone Miner Res 22:569-77. 2007
    ....
  59. ncbi Evidence for increased clinical severity of familial and sporadic Paget's disease of bone in Campania, southern Italy
    Domenico Rendina
    Department of Clinical and Experimental Medicine, Federico II University Medical School, Naples, Italy
    J Bone Miner Res 21:1828-35. 2006
    ..A prevalent involvement of the spine and the skull, the sites preferentially involved in giant cell tumors complicating Paget's disease, was also shown in familial cases from this geographical region...
  60. ncbi Effect of age and gender on the number and distribution of sites in Paget's disease of bone
    M J Haddaway
    Department of Diagnostic Imaging, Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, UK
    Br J Radiol 80:532-6. 2007
    ..The lesser involvement at the axial sites in monostotic disease may lead to overestimation of the decline in PDB based on abdominal radiographs...
  61. ncbi Canine distemper virus induces human osteoclastogenesis through NF-kappaB and sequestosome 1/P62 activation
    Peter L Selby
    Vitamin D Research Group, University School of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester, United Kingdom
    J Bone Miner Res 21:1750-6. 2006
    ..We studied the effects of CDV on osteoclastogenesis in vitro and showed that CDV had a dose-dependent effect on osteoclastogenesis, through a possible mechanism involving activation of NF-kappaB and sequestosome 1/p62...
  62. ncbi Non-isomerized C-telopeptide fragments are highly sensitive markers for monitoring disease activity and treatment efficacy in Paget's disease of bone
    Peter Alexandersen
    Centre for Clinical and Basic Research, Ballerup, Denmark
    J Bone Miner Res 20:588-95. 2005
    ....
  63. ncbi Comparison of different intravenous bisphosphonate regimens for Paget's disease of bone
    Daniela Merlotti
    Department of Internal Medicine, Endocrine, Metabolic Sciences, and Biochemistry, University of Siena, Siena, Italy
    J Bone Miner Res 22:1510-7. 2007
    ..Single neridronate and zoledronate infusion showed a similar efficacy in up to 90% of patients nonresponders to pamidronate...
  64. ncbi Prevalence of Paget's disease of bone in Italy
    Luigi Gennari
    Department of Internal Medicine, Endocrine Metabolic Sciences and Biochemistry, University of Siena, Siena, and Department of Radiology, U O A I S Giovanni Battista Hospital of Torino, Italy
    J Bone Miner Res 20:1845-50. 2005
    ..7% to 2.4%, were higher in males than in females, and slightly differed between the two towns. Unlike previous studies in populations of British descent, no secular trend for a decreasing prevalence emerged...
  65. ncbi Genetics of Paget's disease of bone
    Laetitia Michou
    Clinical Genetics Unit, Hopital Lariboisiere, Paris, France
    Joint Bone Spine 73:243-8. 2006
    ..Detection of a mutation allows evaluation of family members to ensure early diagnosis of the disease before complications develop...
  66. ncbi Paget's disease of bone: the skeletal distribution, complications and quality of life as perceived by patients
    M Seton
    Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Bulfinch 165, 55 Fruit Street, Boston, MA 02114, USA
    Bone 48:281-5. 2011
    ..Paget's disease of bone (PDB) is a focal disorder of bone metabolism with overgrowth of affected bone resulting in the skeletal complications of this disease...
  67. ncbi Novel SQSTM1 mutations in patients with Paget's disease of bone in an unrelated multiethnic American population
    Laetitia Michou
    Department of Medicine, Laval University, CHUQ CHUL Research centre and Division of Rheumatology, CHUQ CHUL, Quebec City, QC, Canada
    Bone 48:456-60. 2011
    ..The SQSTM1 mutation rate in unrelated American patients described in the present study was similar to that reported in European populations...
  68. ncbi Gene expression profile in osteoclasts from patients with Paget's disease of bone
    Laetitia Michou
    Department of Medicine, Laval University, Canada G1V 4G2
    Bone 46:598-603. 2010
    ..They also suggest that the SQSTM1 P392L mutation plays a role in PDB pathogenesis, even at early preclinical stages in healthy carriers of the P392L mutation...
  69. pmc Linkage of Paget disease of bone to a novel region on human chromosome 18q23
    David A Good
    Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, Australia
    Am J Hum Genet 70:517-25. 2002
    ..71, at marker D18S70. Our data are consistent with genetic heterogeneity within the pedigree and indicate that 18q23 harbors a novel susceptibility gene for PDB...
  70. ncbi Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget's disease
    L Alvarez
    Service of Clinical Biochemistry, Hospital Clinic, University of Barcelona, Barcelona, Spain
    Bone 29:447-52. 2001
    ..Data on biological variation are useful for assessing actual changes induced by treatment...
  71. ncbi The majority of the genetic risk for Paget's disease of bone is explained by genetic variants close to the CSF1, OPTN, TM7SF4, and TNFRSF11A genes
    Pui Yan Jenny Chung
    Department of Medical Genetics, University and University Hospital of Antwerp, 2610, Antwerp, Belgium
    Hum Genet 128:615-26. 2010
    ..The calculated cumulative population attributable risk of these four loci turned out to be about 67% in our two populations, indicating that most of the genetic risk for PDB is coming from genetic variants close to these four genes...
  72. ncbi Paget's disease of bone is not associated with common polymorphisms in interleukin-6, interleukin-8 and tumor necrosis factor alpha genes
    Luis Corral-Gudino
    Servicio de Medicina Interna, RETICEF, Hospital Universitario de Salamanca, Los Montalvos s n, Salamanca, Spain
    Cytokine 52:146-50. 2010
    ..Cytokines, specially interleukin (IL)-6, play an important role in the differentiation and activation of osteoclasts and might be involved in osteoblast stimulation in Paget's disease of bone (PDB)...
  73. ncbi Insights into the pathogenesis of Paget's disease
    G David Roodman
    University of Pittsburgh, School of Medicine Hematology Oncology, Pittsburgh, PA, USA
    Ann N Y Acad Sci 1192:176-80. 2010
    ..These studies suggest that both genetic and environmental factors contribute to PD...
  74. pmc VCP/p97 is essential for maturation of ubiquitin-containing autophagosomes and this function is impaired by mutations that cause IBMPFD
    Emilie Tresse
    Department of Developmental Neurobiology, St Jude Children s Research Hospital, Memphis, TN, USA
    Autophagy 6:217-27. 2010
    ..We conclude that VCP is essential for maturation of ubiquitin-containing autophagosomes and that defect in this function may contribute to IBMPFD pathogenesis...
  75. ncbi VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder
    Virginia E Kimonis
    Division of Genetics and Metabolism, Department of Pediatrics, University of California, Irvine, 101 The City Drive, ZOT 4482, Orange, CA 92868, USA
    Biochim Biophys Acta 1782:744-8. 2008
    ..Inclusions seen in the muscle, brain and heart in VCP disease contain ubiquitin, beta amyloid and TDP-43, also seen in other neurodegenerative disorders thus implicating common pathways in their pathogenesis...
  76. ncbi Pathological consequences of VCP mutations on human striated muscle
    Christian U Hübbers
    Institute of Biochemistry I, University of Cologne, Cologne, Germany
    Brain 130:381-93. 2007
    ..The latter findings provide a novel link to VCP carbohydrate interactions in the complex pathology of IBMPFD...
  77. ncbi Structure of the ubiquitin-associated domain of p62 (SQSTM1) and implications for mutations that cause Paget's disease of bone
    Barbara Ciani
    School of Chemistry, University Park, Nottingham NG7 2RD, United Kingdom
    J Biol Chem 278:37409-12. 2003
    ..Thus, phenotypically identical substitution and deletion mutations do not appear to predispose to PDB through a mechanism dependent on a common loss of ubiquitin chain binding by p62...
  78. ncbi Inclusion body myopathy-associated mutations in p97/VCP impair endoplasmic reticulum-associated degradation
    Conrad C Weihl
    Department of Neurology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Hum Mol Genet 15:189-99. 2006
    ..Undegraded mutant DeltaF508-CFTR also accumulates in these aggregates. We conclude that IBMPFD mutations in p97/VCP disrupt ERAD and that this may contribute to the pathogenesis of IBMPFD...
  79. ncbi Recent advances in understanding the molecular basis of Paget disease of bone
    A Goode
    School of Biomedical Sciences, University of Nottingham Medical School, Queen s Medical Centre, Nottingham NG7 2UH, UK
    J Clin Pathol 63:199-203. 2010
    ....
  80. pmc Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease
    Noriyoshi Kurihara
    VA Pittsburgh Healthcare System, Research and Development, Pittsburgh, Pennsylvania 15240, USA
    J Clin Invest 117:133-42. 2007
    ....
  81. pmc Paget disease of bone
    G David Roodman
    Department of Medicine, Division of Hematology Oncology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15240, USA
    J Clin Invest 115:200-8. 2005
    ..In this review, the pathophysiology of PD and evidence for both a genetic and a viral etiology for PD will be discussed...
  82. ncbi Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate
    David Hosking
    City Hospital, Nottingham, UK
    J Bone Miner Res 22:142-8. 2007
    ..This effect is largely independent of pretreatment disease activity and prior bisphosphonate therapy...
  83. ncbi The role of immune cells and inflammatory cytokines in Paget's disease and multiple myeloma
    Lori A Ehrlich
    Department of Medicine Hematology Oncology, University of Pittsburgh, Pittsburgh, PA 15240, USA
    Immunol Rev 208:252-66. 2005
    ..This article discusses the role of immune cells and inflammatory cytokines and chemokines in the increased OCL activity in PD and MM bone disease, as well as the potential role of interleukin-3 in the suppression of OBL activity in MM...
  84. ncbi Autosomal dominant inclusion body myopathy, Paget disease of bone, and frontotemporal dementia
    Virginia E Kimonis
    Division of Genetics, Children s Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA
    Alzheimer Dis Assoc Disord 19:S44-7. 2005
    ..Identification of VCP as the gene causing IBMPFD has important implications for understanding the pathogenesis of neurodegenerative disorders...
  85. ncbi Guidelines for the diagnosis and management of Paget's disease: a UK perspective
    Peter L Selby
    University Department of Medicine, Manchester Royal Infirmary, Manchester, United Kingdom
    J Bone Miner Res 21:P92-3. 2006
  86. ncbi Is the prevalence of Paget's disease of bone decreasing?
    Tim Cundy
    Department of Medicine, University of Auckland, Auckland, New Zealand
    J Bone Miner Res 21:P9-13. 2006
    ..Paget's disease has become less prevalent and patients are presenting later, with less severe disease than previously. These data suggest that environmental factors are important in the etiology of Paget's disease...
  87. pmc Paget disease of bone: mapping of two loci at 5q35-qter and 5q31
    N Laurin
    Molecular Endocrinology and Oncology Research Center, CHUL Research Center, Quebec, QC, Canada G1V 4G2
    Am J Hum Genet 69:528-43. 2001
    ..It is proposed that the 5q35-qter and 5q31 loci be named "PDB3" and "PDB4," respectively...
  88. ncbi Transfer of Paget's disease from one part of the skeleton to another as a result of autogenous bone-grafting: a case report
    Moussa Hamadouche
    Departments of Orthopaedic and Reconstructive Surgery, Hopital Cochin, 27 rue du Faubourg St Jacques, 75014 Paris, France
    J Bone Joint Surg Am 84:2056-61. 2002
  89. ncbi Paget's disease in an archeological population
    J Rogers
    Department of Rheumatology, Bristol Royal Infirmary, United Kingdom
    J Bone Miner Res 17:1127-34. 2002
    ..This is likely caused by the small sample size, but this is by far the greatest number of cases of PDB described in a single skeletal assemblage to date. The distribution of lesions within the skeleton is unchanged...
  90. ncbi Severe hypocalcemia following bisphosphonate treatment in a patient with Paget's disease of bone
    Heather E Whitson
    GRECC, VA Medical Center, Durham, NC 27710, USA
    Bone 39:954-8. 2006
    ..Physicians should be aware of the potential for hypocalcemia when patients with polyostotic Paget's disease and markedly elevated indicators of bone remodeling are initiated on powerful anti-resorptive therapy...
  91. pmc Genetic linkage of Paget disease of the bone to chromosome 18q
    J D Cody
    Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78284, USA
    Am J Hum Genet 61:1117-22. 1997
    ..40, with the genetic marker D18S42, a marker tightly linked to the FEO locus. This demonstrates that the gene(s) responsible for FEO and that for Paget disease are either closely linked or the same locus...
  92. ncbi An Italian family with inclusion-body myopathy and frontotemporal dementia due to mutation in the VCP gene
    Teresa Gidaro
    Department of Neuroscience, Catholic University, L go A Gemelli 8, 00168 Rome, Italy
    Muscle Nerve 37:111-4. 2008
    ..Our study demonstrates that VCP mutations are found in patients of Italian background and may lead to a variable clinical phenotype even within the same kinship...
  93. ncbi [Italian guidelines for the diagnosis and treatment of Paget's disease of bone]
    S Adami
    Reumatologia, Universita di Verona, Verona, Italia
    Reumatismo 59:153-68. 2007
    ..The document provides the most updated recommendations based primarily on the "evidence-based- medicine" but also on the Italian regulation for the diagnostic procedures and on the available medical treatments...
  94. ncbi Gene expression profiling in Paget's disease of bone: upregulation of interferon signaling pathways in pagetic monocytes and lymphocytes
    Zsolt B Nagy
    National Institute of Rheumatology and Physiotherapy, Budapest, Hungary
    J Bone Miner Res 23:253-9. 2008
    ..We found a significant overexpression of the genes of the IFN pathway along with a downregulation of tnf-alpha. Our result suggest that IFN-mediated signaling may play important roles in aberrant osteoclastogenesis of PD...
  95. ncbi Inclusion body myopathy and Paget disease is linked to a novel mutation in the VCP gene
    D Haubenberger
    Department of Neurology, Medical University of Vienna, Vienna, Austria
    Neurology 65:1304-5. 2005
    ....
  96. pmc Valosin-containing protein disease: inclusion body myopathy with Paget's disease of the bone and fronto-temporal dementia
    Conrad C Weihl
    Department of Neurology, Washington University School of Medicine, Saint Louis, MO 63110, USA
    Neuromuscul Disord 19:308-15. 2009
    ....
  97. ncbi Characterization of a non-UBA domain missense mutation of sequestosome 1 (SQSTM1) in Paget's disease of bone
    Dereen Najat
    School of Biomedical Sciences, University of Nottingham, Nottingham, United Kingdom
    J Bone Miner Res 24:632-42. 2009
    ....
  98. ncbi A novel mutation in the VCP gene (G157R) in a German family with inclusion-body myopathy with Paget disease of bone and frontotemporal dementia
    Atbin Djamshidian
    Department of Neurology, Medical University of Vienna Währinger Gürtel 18 20, Vienna A 1097, Austria
    Muscle Nerve 39:389-91. 2009
    ..Two family members also showed signs of early hearing impairment, which was confirmed to be sensorineural in one person, a symptom not yet described in the context of IBMPFD...
  99. ncbi Transgenic mice expressing mutant forms VCP/p97 recapitulate the full spectrum of IBMPFD including degeneration in muscle, brain and bone
    Sara K Custer
    Department of Developmental Neurobiology, St Jude Children s Research, Hospital, Memphis, TN 38105, USA
    Hum Mol Genet 19:1741-55. 2010
    ..In vitro studies indicate that mutant VCP causes inappropriate activation of the NF-kappaB signaling cascade, which could contribute to the mechanism of pathogenesis in multiple tissues including muscle, bone and brain...
  100. ncbi A comparison of in situ hybridisation, reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ-RT-PCR for the detection of canine distemper virus RNA in Paget's disease
    Judith A Hoyland
    Laboratory Medicine Academic Group, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT, UK
    J Virol Methods 109:253-9. 2003
    ..These findings also have wider implications for other studies investigating viral expression...
  101. pmc Morbidity and mortality associated with Paget's disease of bone: a population-based study
    Robert A Wermers
    Division of Endocrinology, Metabolism and Nutrition, Department of Internal Medicine, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA
    J Bone Miner Res 23:819-25. 2008
    ..We examined morbidity and mortality associated with this condition in a large inception cohort of Olmsted County, MN, residents with a new diagnosis of Paget's disease from 1950 through 1994...

Research Grants21

  1. Translational Studies in VCP Inclusion Body Myopathy with Paget Disease of Bone
    Virginia Kimonis; Fiscal Year: 2009
    ..abstract_text> ..
  2. CLONING NOVEL GENES FOR PAGETS DISEASE AND OSTEOSARCOMA
    Marc Hansen; Fiscal Year: 2001
    DESCRIPTION (Adapted from the Applicant's Abstract): Paget's disease of bone, or osteitis deformans, is a bone disorder characterized by rapid bone remodeling, resulting in abnormal bone formation...
  3. Clinical & Molecular Analysis of Neuromuscular Disorders
    Virginia Kimonis; Fiscal Year: 2001
    ..The suggested training will provide the PI with skills necessary to investigate the clinical and basic molecular pathogenesis of these disorders and aid in the development of novel treatment protocols. ..
  4. Characterizing the Role of VCP in Paget's Disease of the Bone
    Giles Watts; Fiscal Year: 2009
    ..In part 2, I will test the hypothesis that it is a disruption of the basal macroautophagy pathway that is the underlying molecular lesion that causes Paget disease of bone. ..
  5. TWO X-LINKED GENES THAT REGULATE MINERAL HOMEOSTASIS
    Michael Whyte; Fiscal Year: 2002
    ....
  6. Genetic basis of myopathy with Paget disease of bone
    Virginia Kimonis; Fiscal Year: 2008
    ..e. effect on ATPase activity, protein-protein interactions, and hexamer formation). Study the VCP specific pathways in C2C12 cell lines (stably transfected wt and R155H VCP) during differentiation and under stress conditions...
  7. GENE CAUSING PAGET & LIMB-GIRDLE MUSCULAR DYSTROPHY
    Virginia Kimonis; Fiscal Year: 2003
    ..Delineation of the genetic component responsible for the LGMD/PDB phenotype should promise similar insight and facilitate in the design of novel treatment protocols for the two disorders. ..
  8. Characterization of Familial Myopathy & Paget Disease
    Virginia Kimonis; Fiscal Year: 2005
    ..Elucidation of the genetic defect will help us understand the pathogenesis of this multifaceted disorder and hopefully result in specific therapy. ..
  9. INHIBITION OF OSTEOCLAST ACTIVITY BY OIP-1/HSCAL
    SAKAMURI REDDY; Fiscal Year: 2008
    ..abstract_text> ..
  10. FACTORS INFLUENCING BONE METABOLISM
    Lawrence Raisz; Fiscal Year: 2008
    ..In addition, signal transduction pathways for enhanced osteoclastogenesis will be examined. ..
  11. Remodeling Extracellular Matrix:Degradation of Collagen
    Stephen Krane; Fiscal Year: 2008
    ..We will analyze the skeletal and extraskeletal phenotype of mice with a null mutation in the "neutrophil" collagenase, MMP-8, another collagenase expressed in the skeleton, as well as mice with double null MMP-8/MMP-13. ..
  12. METABOLISM IN NORMAL AND OSTEOARTHRITIC CARTILAGE
    Henry Mankin; Fiscal Year: 2001
    ..It is further speculated that the study of serine proteinases produced by OA cartilage may have strong implications for the management of this debilitating disease. ..
  13. MECHANISMS OF TNF RECEPTOR MEDIATED OSTEOCLASTOGENSIS
    Yousef Abu Amer; Fiscal Year: 2003
    ..The specific aims of the proposal are (1) to determine the mechanisms by which p55r promotes osteoclastogenesis, and (2) to determine the mechanisms by which p75r suppresses osteoclastogenesis. ..
  14. Prevention of Postmenopausal Bone Loss with Nitric Oxide
    Sunil Wimalawansa; Fiscal Year: 2007
    ..The study will also pave the way for the future, for providing more acceptable, affordable and cost- effective therapies for the prevention of postmenopausalosteoporosis. ..
  15. PATHOBIOLOGY OF THE OSTEOCLAST IN PAGETS DISEASE
    G Roodman; Fiscal Year: 2002
    ..abstract_text> ..
  16. Mechanisms of Tau-Based Neurodegeneration
    Mark Forman; Fiscal Year: 2005
    ..This proposal will also facilitate my transition from a trainee to a fully independent experimental neuropathologist. ..
  17. Paget's Disease of Bone/Dysplasia:Advances/Challenges
    G Roodman; Fiscal Year: 2006
    ..to become aware of the effectiveness of the various drugs that can be used to treat the two disorders; 5.) to understand the role of surgery in managing the two disorders. ..
  18. OSTEOCLASTS FROM TRANSGENIC MICE
    G Roodman; Fiscal Year: 2009
    ..Our long-term goal will be to characterize the role of ADAM8/a9b1 in the bone destruction which accompanies collagen induced arthritis, which will be started in grant year 5. ..
  19. DEVELOPMENTAL ASPECTS OF OSTEOCLAST FORMATION IN VITRO
    G Roodman; Fiscal Year: 2005
    ....
  20. Program Project Grant-Pathobiology of Paget's Disease
    G Roodman; Fiscal Year: 2007
    ..The knowledge gained from this P01 grant will offer important insights for normal bone cell biology especially for understanding the paracrine regulation of osteoblasts by OCLs. ..