Carl R Flannery

Summary

Affiliation: Wyeth Research
Country: USA

Publications

  1. ncbi MMPs and ADAMTSs: functional studies
    Carl R Flannery
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    Front Biosci 11:544-69. 2006
  2. pmc Usurped SLRPs: novel arthritis biomarkers exposed by catabolism of small leucine-rich proteoglycans?
    Carl R Flannery
    Wyeth Research, Cambridge, MA, USA
    Arthritis Res Ther 8:106. 2006
  3. doi Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin
    Carl R Flannery
    Wyeth Research, Cambridge, Massachusetts, USA
    Arthritis Rheum 60:840-7. 2009
  4. ncbi Novel therapies in OA
    Carl R Flannery
    Pfizer, 200 CambridgePark Drive, Cambridge, MA 02140, USA
    Curr Drug Targets 11:614-9. 2010
  5. ncbi Autocatalytic cleavage of ADAMTS-4 (Aggrecanase-1) reveals multiple glycosaminoglycan-binding sites
    Carl R Flannery
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Biol Chem 277:42775-80. 2002
  6. ncbi Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis
    Sonya S Glasson
    Department of Women s Health and Bone, Wyeth Research, 200 CambridgePark Drive, Cambridge, Massachusetts 02140, USA
    Nature 434:644-8. 2005
  7. ncbi Release of hyaluronan and hyaladherins (aggrecan G1 domain and link proteins) from articular cartilage exposed to ADAMTS-4 (aggrecanase 1) or ADAMTS-5 (aggrecanase 2)
    Priya S Chockalingam
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    Arthritis Rheum 50:2839-48. 2004
  8. ncbi Characterization of and osteoarthritis susceptibility in ADAMTS-4-knockout mice
    Sonya S Glasson
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    Arthritis Rheum 50:2547-58. 2004
  9. pmc Identification of a novel HtrA1-susceptible cleavage site in human aggrecan: evidence for the involvement of HtrA1 in aggrecan proteolysis in vivo
    Angela Chamberland
    Department of Tissue Repair, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Biol Chem 284:27352-9. 2009
  10. ncbi Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: comparative analyses with ADAMTS-5, -9, -16 and -18
    Weilan Zeng
    Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    Biochim Biophys Acta 1760:517-24. 2006

Collaborators

Detail Information

Publications29

  1. ncbi MMPs and ADAMTSs: functional studies
    Carl R Flannery
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    Front Biosci 11:544-69. 2006
    ....
  2. pmc Usurped SLRPs: novel arthritis biomarkers exposed by catabolism of small leucine-rich proteoglycans?
    Carl R Flannery
    Wyeth Research, Cambridge, MA, USA
    Arthritis Res Ther 8:106. 2006
    ....
  3. doi Prevention of cartilage degeneration in a rat model of osteoarthritis by intraarticular treatment with recombinant lubricin
    Carl R Flannery
    Wyeth Research, Cambridge, Massachusetts, USA
    Arthritis Rheum 60:840-7. 2009
    ..This study was undertaken to generate and characterize a novel recombinant lubricin protein construct, LUB:1, and to evaluate its therapeutic efficacy following intraarticular delivery in a rat model of osteoarthritis (OA)...
  4. ncbi Novel therapies in OA
    Carl R Flannery
    Pfizer, 200 CambridgePark Drive, Cambridge, MA 02140, USA
    Curr Drug Targets 11:614-9. 2010
    ....
  5. ncbi Autocatalytic cleavage of ADAMTS-4 (Aggrecanase-1) reveals multiple glycosaminoglycan-binding sites
    Carl R Flannery
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Biol Chem 277:42775-80. 2002
    ....
  6. ncbi Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis
    Sonya S Glasson
    Department of Women s Health and Bone, Wyeth Research, 200 CambridgePark Drive, Cambridge, Massachusetts 02140, USA
    Nature 434:644-8. 2005
    ..These results demonstrate that ADAMTS5 is the primary 'aggrecanase' responsible for aggrecan degradation in a murine model of osteoarthritis, and suggest rational strategies for therapeutic intervention in osteoarthritis...
  7. ncbi Release of hyaluronan and hyaladherins (aggrecan G1 domain and link proteins) from articular cartilage exposed to ADAMTS-4 (aggrecanase 1) or ADAMTS-5 (aggrecanase 2)
    Priya S Chockalingam
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    Arthritis Rheum 50:2839-48. 2004
    ....
  8. ncbi Characterization of and osteoarthritis susceptibility in ADAMTS-4-knockout mice
    Sonya S Glasson
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    Arthritis Rheum 50:2547-58. 2004
    ..To determine the importance of the enzymatic activity of ADAMTS-4 in normal growth and development and to evaluate the role of ADAMTS-4 in the progression of osteoarthritis (OA)...
  9. pmc Identification of a novel HtrA1-susceptible cleavage site in human aggrecan: evidence for the involvement of HtrA1 in aggrecan proteolysis in vivo
    Angela Chamberland
    Department of Tissue Repair, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Biol Chem 284:27352-9. 2009
    ....
  10. ncbi Glycosaminoglycan-binding properties and aggrecanase activities of truncated ADAMTSs: comparative analyses with ADAMTS-5, -9, -16 and -18
    Weilan Zeng
    Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA
    Biochim Biophys Acta 1760:517-24. 2006
    ..Similarly, GAG-binding ability, irrespective of the presence of a TSR-1 domain, does not necessarily empower truncated ADAMTSs with proficient aggrecanase activity...
  11. ncbi 5-((1H-pyrazol-4-yl)methylene)-2-thioxothiazolidin-4-one inhibitors of ADAMTS-5
    Adam M Gilbert
    Exploratory Medicinal Chemistry, Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 17:1189-92. 2007
    ..Compound 12 is noteworthy in that it has an ADAMTS-5 IC50: 1.1 microM and shows >40-fold functional selectivity over ADAMTS-4 (aggrecanase-1)...
  12. doi Modulation of lubricin biosynthesis and tissue surface properties following cartilage mechanical injury
    Aled R C Jones
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    Arthritis Rheum 60:133-42. 2009
    ..To evaluate the effects of injurious compression on the biosynthesis of lubricin at different depths within articular cartilage and to examine alterations in structure and function of the articular surface following mechanical injury...
  13. ncbi 5'-Phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (aggrecanase-2)
    Matthew G Bursavich
    Exploratory Medicinal Chemistry, Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 17:5630-3. 2007
    ..This series of compounds represents progress toward a selective ADAMTS-5 inhibitor as a disease modifying osteoarthritis drug...
  14. doi N-((8-hydroxy-5-substituted-quinolin-7-yl)(phenyl)methyl)-2-phenyloxy/amino-acetamide inhibitors of ADAMTS-5 (Aggrecanase-2)
    Adam M Gilbert
    Exploratory Medicinal Chemistry, Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 18:6454-7. 2008
    ..This series of compounds represents progress towards selective ADAMTS-5 inhibitors as disease modifying osteoarthritis agents...
  15. ncbi Binding and localization of recombinant lubricin to articular cartilage surfaces
    Aled R C Jones
    Department of Women s Health and Musculoskeletal Biology, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Orthop Res 25:283-92. 2007
    ..These findings help identify additional key attributes contributing to lubricin functionality, which would be expected to be instrumental in maintaining joint homeostasis...
  16. pmc Disposition of human recombinant lubricin in naive rats and in a rat model of post-traumatic arthritis after intra-articular or intravenous administration
    Yulia Vugmeyster
    Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc, Pfizer Inc, Andover, Massachusetts, USA
    AAPS J 14:97-104. 2012
    ..7 h. Overall, LUB:1 has met a desired disposition profile of a potential therapeutic intended for an IA administration: target tissue (knee) retention and fast elimination from the systemic circulation after a single IA or IV dose...
  17. ncbi ADAMTS-8 exhibits aggrecanase activity and is expressed in human articular cartilage
    Lisa A Collins-Racie
    Department of Discovery Medicine, Wyeth Research, Cambridge, MA 02140, USA
    Matrix Biol 23:219-30. 2004
    ..In addition, expression analyses demonstrated the presence of ADAMTS-8 mRNA transcripts in normal and osteoarthritic human cartilage...
  18. pmc LXR modulation blocks prostaglandin E2 production and matrix degradation in cartilage and alleviates pain in a rat osteoarthritis model
    Ning Li
    Pfizer BioTherapeutics Research, Cambridge, MA 02140, USA
    Proc Natl Acad Sci U S A 107:3734-9. 2010
    ..Consistent with our in vitro observations, oral administration of GW3965 potently alleviated joint pain in a rat meniscal tear model of osteoarthritis...
  19. pmc Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage
    Lisha Patel
    Tissue Repair, BioTherapeutics Research and Development, Pfizer, Cambridge, MA, USA
    BMC Musculoskelet Disord 12:164. 2011
    ..The effect of TN-C on proteoglycan loss from articular cartilage in culture was also assessed...
  20. ncbi Comparative proteomic characterization of articular cartilage tissue from normal donors and patients with osteoarthritis
    Jiang Wu
    Wyeth Research, Cambridge, Massachusetts 02140, USA
    Arthritis Rheum 56:3675-84. 2007
    ..To identify potential molecular mediators and biomarkers for osteoarthritis (OA), through comparative proteomic analysis of articular cartilage tissue obtained from normal donors without OA (n = 7) and patients with OA (n = 7)...
  21. pmc Serine Protease HTRA1 Antagonizes Transforming Growth Factor-β Signaling by Cleaving Its Receptors and Loss of HTRA1 In Vivo Enhances Bone Formation
    Julie R Graham
    Inflammation and Remodeling Research Unit, Pfizer BioTherapeutics Research, Cambridge, Massachusetts, United States of America
    PLoS ONE 8:e74094. 2013
    ..This study has identified a novel regulatory mechanism by which HTRA1 antagonizes TGF-β signaling, and has shown that HTRA1 plays a key role in the regulation of bone formation. ..
  22. ncbi Synthesis and evaluation of aryl thioxothiazolidinone inhibitors of ADAMTS-5 (Aggrecanase-2)
    Matthew G Bursavich
    Exploratory Medicinal Chemistry, Chemical and Screening Sciences, Wyeth Research, 401 North Middletown Road, Pearl River, NY 10965, USA
    Bioorg Med Chem Lett 17:1185-8. 2007
    ..This series of compounds represents steps toward a metalloprotease inhibitor as a disease-modifying osteoarthritis drug...
  23. doi Catabolic responses of chondrocyte-seeded peptide hydrogel to dynamic compression
    John D Kisiday
    Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA
    Ann Biomed Eng 37:1368-75. 2009
    ..These data suggest that partially mature cartilage tissue engineering constructs may be susceptible to catabolic degradation...
  24. pmc Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis
    Allan A Young
    Raymond Purves Research Laboratory, Institute of Bone and Joint Research, Royal North Shore Hospital, University of Sydney, Pacific Highway, St Leonards, NSW 2065, Australia
    Arthritis Res Ther 8:R41. 2006
    ..01) decrease in corresponding mRNA levels. Early loss of proteoglycan 4 from the cartilage surface in association with a decrease in its expression by superficial-zone chondrocytes might have a role in the pathogenesis of osteoarthritis...
  25. ncbi Effects of n-3 fatty acids on cartilage metabolism
    Clare L Curtis
    Cardiff School of Biosciences, Cardiff University, UK
    Proc Nutr Soc 61:381-9. 2002
    ..Collectively, our data provide evidence supporting dietary supplementation of n-3 PUFA, which in turn may have a beneficial effect of slowing and reducing inflammation in the pathogenesis of degenerative joint diseases in man...
  26. ncbi Pathologic indicators of degradation and inflammation in human osteoarthritic cartilage are abrogated by exposure to n-3 fatty acids
    Clare L Curtis
    Connective Tissue Biology Laboratories, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, Wales, UK
    Arthritis Rheum 46:1544-53. 2002
    ..To determine if n-3 polyunsaturated fatty acid (PUFA) supplementation (versus treatment with n-6 polyunsaturated or other fatty acid supplements) affects the metabolism of osteoarthritic (OA) cartilage...
  27. ncbi Matrix metalloproteinases are involved in C-terminal and interglobular domain processing of cartilage aggrecan in late stage cartilage degradation
    Christopher B Little
    Connective Tissue Biology Laboratory, Cardiff School of Biosciences, Cardiff University, Museum Avenue, Cardiff, CF10 3US, Wales, UK
    Matrix Biol 21:271-88. 2002
    ..Furthermore, analysis of aggrecan metabolites resulting from both C-terminal and IGD cleavage by MMPs may prove useful in monitoring different stages in the progression of cartilage degeneration...
  28. ncbi Cyclosporin A inhibition of aggrecanase-mediated proteoglycan catabolism in articular cartilage
    Chris B Little
    Connective Tissue Biology Laboratories, Cardiff School of Biosciences, Cardiff University, UK
    Arthritis Rheum 46:124-9. 2002
    ....
  29. ncbi Immunolocalisation and expression of proteoglycan 4 (cartilage superficial zone proteoglycan) in tendon
    Sarah G Rees
    Connective Tissue Biology Laboratories, Cardiff School of Biosciences, Cardiff University, Museum Avenue, CF10 3US, Cardiff, UK
    Matrix Biol 21:593-602. 2002
    ..Structural modifications to SZP, together with a reduction in synthesis during tendon inflammation with injury and disease may account for the formation of tendon adhesions and contribute to the overall dysfunction of the tissue...