G A Rodan

Summary

Affiliation: Merck Research Laboratories
Country: USA

Publications

  1. ncbi Therapeutic approaches to bone diseases
    G A Rodan
    Merck Research Laboratories, West Point, PA 19486, USA St Vincent s Institute of Medical Research, Melbourne 3065, Australia
    Science 289:1508-14. 2000
  2. ncbi Bisphosphonate mechanism of action
    Gideon A Rodan
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486, USA
    Curr Mol Med 2:571-7. 2002
  3. ncbi Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol/lipoproteins
    E Luegmayr
    Molecular Endocrinology and Bone Biology, Merck and Co, Inc, West Point, PA 19486, USA
    Cell Death Differ 11:S108-18. 2004
  4. pmc PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of alpha(v)beta3 integrin, and phosphorylated by src kinase
    L T Duong
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Clin Invest 102:881-92. 1998
  5. ncbi Inhibition of osteoclast function by adenovirus expressing antisense protein-tyrosine kinase 2
    L T Duong
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 276:7484-92. 2001
  6. pmc Convergence of alpha(v)beta(3) integrin- and macrophage colony stimulating factor-mediated signals on phospholipase Cgamma in prefusion osteoclasts
    I Nakamura
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Cell Biol 152:361-73. 2001
  7. ncbi Abnormal localisation and hyperclustering of (alpha)(V)(beta)(3) integrins and associated proteins in Src-deficient or tyrphostin A9-treated osteoclasts
    P T Lakkakorpi
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Cell Sci 114:149-160. 2001
  8. ncbi Bisphosphonates act directly on the osteoclast to induce caspase cleavage of mst1 kinase during apoptosis. A link between inhibition of the mevalonate pathway and regulation of an apoptosis-promoting kinase
    A A Reszka
    Department of Bone Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 274:34967-73. 1999
  9. ncbi M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase
    H Glantschnig
    Bone Biology and Osteoporosis Research, Merck and Co, Inc, West Point, PA 19486, USA
    Cell Death Differ 10:1165-77. 2003
  10. ncbi PYK2 is an adhesion kinase in macrophages, localized in podosomes and activated by beta(2)-integrin ligation
    L T Duong
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Cell Motil Cytoskeleton 47:174-88. 2000

Collaborators

Detail Information

Publications67

  1. ncbi Therapeutic approaches to bone diseases
    G A Rodan
    Merck Research Laboratories, West Point, PA 19486, USA St Vincent s Institute of Medical Research, Melbourne 3065, Australia
    Science 289:1508-14. 2000
    ..Far less attention has been paid to promoting bone formation with, for example, growth factors or hormones, an approach that would be a valuable adjunct therapy for patients receiving inhibitors of bone resorption...
  2. ncbi Bisphosphonate mechanism of action
    Gideon A Rodan
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486, USA
    Curr Mol Med 2:571-7. 2002
    ..As a result, there is a reduction in the lipid geranylgeranyl diphosphate, which prenylates GTPases required for cytoskeletal organization and vesicular traffic in the osteoclast, leading to osteoclast inactivation...
  3. ncbi Osteoclast formation, survival and morphology are highly dependent on exogenous cholesterol/lipoproteins
    E Luegmayr
    Molecular Endocrinology and Bone Biology, Merck and Co, Inc, West Point, PA 19486, USA
    Cell Death Differ 11:S108-18. 2004
    ..Cell Death and Differentiation (2004) 11, S108-S118. doi:10.1038/sj.cdd.4401399 Published online 12 March 2004..
  4. pmc PYK2 in osteoclasts is an adhesion kinase, localized in the sealing zone, activated by ligation of alpha(v)beta3 integrin, and phosphorylated by src kinase
    L T Duong
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Clin Invest 102:881-92. 1998
    ..Taken together, these findings suggest that Src-dependent tyrosine phosphorylation of PYK2 is involved in the adhesion-induced formation of the sealing zone, required for osteoclastic bone resorption...
  5. ncbi Inhibition of osteoclast function by adenovirus expressing antisense protein-tyrosine kinase 2
    L T Duong
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 276:7484-92. 2001
    ..Taken together, these findings support the hypothesis that PYK2 plays a central role in the adhesion-dependent cytoskeletal organization and sealing zone formation required for osteoclastic bone resorption...
  6. pmc Convergence of alpha(v)beta(3) integrin- and macrophage colony stimulating factor-mediated signals on phospholipase Cgamma in prefusion osteoclasts
    I Nakamura
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Cell Biol 152:361-73. 2001
    ..M-CSF-initiated signaling modulates the alpha(v)beta(3) integrin-mediated cytoskeletal reorganization in prefusion osteoclasts in the absence of c-Src, possibly via PLC-gamma...
  7. ncbi Abnormal localisation and hyperclustering of (alpha)(V)(beta)(3) integrins and associated proteins in Src-deficient or tyrphostin A9-treated osteoclasts
    P T Lakkakorpi
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Cell Sci 114:149-160. 2001
    ..Taken together, these findings suggest that normal localisation of (alpha)(v)(beta)(3) and recruitment of its downstream effectors to the appropriate compartments of the osteoclast during resorption depend on Src kinase activity...
  8. ncbi Bisphosphonates act directly on the osteoclast to induce caspase cleavage of mst1 kinase during apoptosis. A link between inhibition of the mevalonate pathway and regulation of an apoptosis-promoting kinase
    A A Reszka
    Department of Bone Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 274:34967-73. 1999
    ..For alendronate and risedronate, these events seem to be downstream of inhibition of geranylgeranylation...
  9. ncbi M-CSF, TNFalpha and RANK ligand promote osteoclast survival by signaling through mTOR/S6 kinase
    H Glantschnig
    Bone Biology and Osteoporosis Research, Merck and Co, Inc, West Point, PA 19486, USA
    Cell Death Differ 10:1165-77. 2003
    ..This study thus identifies mTOR/S6K as an essential signaling pathway engaged in the stimulation of cell survival in osteoclasts...
  10. ncbi PYK2 is an adhesion kinase in macrophages, localized in podosomes and activated by beta(2)-integrin ligation
    L T Duong
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Cell Motil Cytoskeleton 47:174-88. 2000
    ..We propose that Pyk2 is functionally linked to the formation of podosomes where it mediates the integrin-cytoskeleton interface and regulates cell spreading and migration...
  11. ncbi Alendronate inhibition of protein-tyrosine-phosphatase-meg1
    E E Opas
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486, U S A
    Biochem Pharmacol 54:721-7. 1997
    ..These observations show substrate- and enzyme-specific PTP inhibition by alendronate and support the possibility that a certain PTP(s) may be the molecular target for alendronate action...
  12. ncbi Phosphatidylinositol 3-kinase association with the osteoclast cytoskeleton, and its involvement in osteoclast attachment and spreading
    P T Lakkakorpi
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratory, West Point, Pennsylvania 19486, USA
    Exp Cell Res 237:296-306. 1997
    ..Finally, PI3-kinase coimmunoprecipitated with alpha v beta 3 integrin from osteoclasts...
  13. ncbi Human protein tyrosine phosphatase-sigma: alternative splicing and inhibition by bisphosphonates
    N Endo
    Department of Bone Biology, Merck Research Laboratories, West Point, Pennsylvania, USA
    J Bone Miner Res 11:535-43. 1996
    ..These findings show tissue-specific alternative splicing of PTP sigma and suggest that PTPs are putative targets of bisphosphonate action...
  14. ncbi Transcription control and neuronal differentiation by agents that activate the LXR nuclear receptor family
    A Schmidt
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486, USA
    Mol Cell Endocrinol 155:51-60. 1999
    ..These results suggest that the hydroxycholesterol signaling pathway has a complex effect on transcription that mediates the activity of TOFA and hydroxycholesterol on neuronal differentiation in pheochromocytoma cells...
  15. ncbi Inhibition of bone resorption by alendronate and risedronate does not require osteoclast apoptosis
    J M Halasy-Nagy
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486, USA
    Bone 29:553-9. 2001
    ....
  16. ncbi Integrin-mediated signaling in the regulation of osteoclast adhesion and activation
    L T Duong
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, PA 19486, USA
    Front Biosci 3:d757-68. 1998
    ..They emerged however as key players in linking the adhesion of osteoclasts to the bone matrix, to cytoskeletal organization, and to the polarization and activation of these cells for bone resorption...
  17. ncbi Identification of a new member of the steroid hormone receptor superfamily that is activated by a peroxisome proliferator and fatty acids
    A Schmidt
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486
    Mol Endocrinol 6:1634-41. 1992
    ..Similar stimulation was observed with arachidonic and oleic acid (100-250 microM)...
  18. ncbi Nitrogen-bisphosphonates block retinoblastoma phosphorylation and cell growth by inhibiting the cholesterol biosynthetic pathway in a keratinocyte model for esophageal irritation
    A A Reszka
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Mol Pharmacol 59:193-202. 2001
    ....
  19. ncbi Effects of retinoic acid on alkaline phosphatase messenger ribonucleic acid, catecholamine receptors, and G proteins in ROS 17/2.8 cells
    Y Imai
    Department of Bone Biology and Osteoporosis Research, Merck, Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486
    Endocrinology 122:456-63. 1988
    ..Retinoids thus inhibit the same features that are promoted by glucocorticoids in ROS 17/2.8 cells. These features seem to be subject to coordinate regulation, probably at the pretranslational level...
  20. ncbi Msx-2/Hox 8.1: a transcriptional regulator of the rat osteocalcin promoter
    D A Towler
    Department of Bone Biology and Osteoporosis Research, Merck Merck Research Laboratories, West Point, Pennsylvania 19486
    Mol Endocrinol 8:1484-93. 1994
    ..These data suggest that Msx-2 may play a role in the transcriptional regulation of the osteoblast phenotype during development in the morphogenetic fields where it is expressed...
  21. ncbi Bone mass homeostasis and bisphosphonate action
    G A Rodan
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA, USA
    Bone 20:1-4. 1997
    ....
  22. ncbi Integrins and signaling in osteoclast function
    L T Duong
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, PA 19486, USA
    Matrix Biol 19:97-105. 2000
    ....
  23. pmc Protein-tyrosine phosphatase activity regulates osteoclast formation and function: inhibition by alendronate
    A Schmidt
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486, USA
    Proc Natl Acad Sci U S A 93:3068-73. 1996
    ..05 microM, respectively. These findings suggest that tyrosine phosphatase activity plays an important role in osteoclast formation and function and is a putative molecular target of bisphosphonate action...
  24. ncbi Mechanisms of action of bisphosphonates
    G A Rodan
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Annu Rev Pharmacol Toxicol 38:375-88. 1998
    ..At the molecular level, it is not known if BPs act on a single or multiple targets. Enzymes in the cholesterol biosynthesis pathway and protein tyrosine phosphatases were shown to be inhibited by BPs...
  25. ncbi Stable association of PYK2 and p130(Cas) in osteoclasts and their co-localization in the sealing zone
    P T Lakkakorpi
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 274:4900-7. 1999
    ..These findings suggest that p130(Cas) and its association with PYK2 may play an important role in the adhesion-dependent signaling that leads to cytoskeletal reorganization and formation of the sealing zone during osteoclast activation...
  26. ncbi NER, a new member of the gene family encoding the human steroid hormone nuclear receptor
    D M Shinar
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486
    Gene 147:273-6. 1994
    ..A single transcript of 2.3 kb was detected in all cells and tissues tested. Although no ligand was identified for NER-I, its wide distribution may indicate that this novel steroid hormone NR may play a basic role in cell function...
  27. ncbi The alphavbeta3 integrin regulates alpha5beta1-mediated cell migration toward fibronectin
    K O Simon
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 272:29380-9. 1997
    ..These findings demonstrate alphavbeta3 regulation of alpha5beta1-mediated cell migration and suggest that the beta3 transmembrane domain is essential for this function...
  28. ncbi Prostaglandin receptor EP(4) mediates the bone anabolic effects of PGE(2)
    M Machwate
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Mol Pharmacol 60:36-41. 2001
    ..The pharmacological evidence presented here provides strong support for the hypothesis that the bone anabolic effect of PGE(2) in rats is mediated by the EP(4) receptor...
  29. ncbi Characterization of the rat osteocalcin gene: stimulation of promoter activity by 1,25-dihydroxyvitamin D3
    K G Yoon
    Department of Bone Biology and Osteoporosis Research, Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486
    Biochemistry 27:8521-6. 1988
    ....
  30. pmc Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: evidence for the alternative splicing of a single-copy gene
    M A Thiede
    Department of Biological Research, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486
    Proc Natl Acad Sci U S A 85:4605-9. 1988
    ..In addition, the 3' untranslated sequence of the cDNA described here has significant similarity to the c-myc protooncogene...
  31. ncbi Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue
    M A Thiede
    Department of Bone Biology and Osteoporosis Research, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486
    Science 242:278-80. 1988
    ..These findings suggest that PTH-LP plays a physiological role in lactation, possibly as a hormone for the mobilization or transfer (or both) of calcium to the milk...
  32. ncbi Stimulation of mouse osteopontin promoter by v-Src is mediated by a CCAAT box-binding factor
    K i Tezuka
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 271:22713-7. 1996
    ..These findings suggest that the elevated osteopontin expression in transformed cells could be due, at least in part, to v-Src stimulation of the osteopontin promoter and that this effect is mediated by a CBF-like factor...
  33. pmc Structure and expression of rat osteosarcoma (ROS 17/2.8) alkaline phosphatase: product of a single copy gene
    M A Thiede
    Department of Bone Biology and Osteoporosis Research, Merck Sharp and Dohme Research Laboratories, West Point, PA 19486
    Proc Natl Acad Sci U S A 85:319-23. 1988
    ..8 osteosarcoma and various rat tissues, excluding the intestine, is the product of the same single copy gene...
  34. ncbi Relative binding affinities of bisphosphonates for human bone and relationship to antiresorptive efficacy
    Chih Tai Leu
    Department of Molecular Endocrinology and Bone Biology, Merck Research Laboratories, West Point, PA 19486, USA
    Bone 38:628-36. 2006
    ..These findings suggest that most clinically tested BPs may have similar affinities for human bone. For those with reduced affinity, this may translate into lower potency that necessitates higher dosing...
  35. ncbi Nonpeptide alphavbeta3 antagonists. 8. In vitro and in vivo evaluation of a potent alphavbeta3 antagonist for the prevention and treatment of osteoporosis
    John H Hutchinson
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Med Chem 46:4790-8. 2003
    ..These products proved useful in the identification of active metabolites generated by either in vitro or in vivo metabolism...
  36. ncbi Non-peptide alpha(v)beta(3) antagonists: identification of potent, chain-shortened RGD mimetics that incorporate a central pyrrolidinone constraint
    James J Perkins
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 13:4285-8. 2003
    ..One member of this set was demonstrated to be effective in reducing bone resorption in rats...
  37. ncbi Regulatory mechanism of osteoclast activation
    Ichiro Nakamura
    Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, Japan
    J Electron Microsc (Tokyo) 52:527-33. 2003
    ..In this article, we review the regulatory mechanism of osteoclast activation...
  38. ncbi Non-peptide alpha v beta 3 antagonists. Part 7: 3-Substituted tetrahydro-naphthyridine derivatives
    Jiabing Wang
    Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 4, West Point, PA 19486, USA
    Bioorg Med Chem Lett 14:1049-52. 2004
    ..96, R(2)=0.959). Electron-withdrawing groups at the 3-position of the tetrahydro-[1,8]naphthyridine decreased potency while electron-donating groups enhanced potency...
  39. ncbi The role of subchondral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model
    Tadashi Hayami
    Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Arthritis Rheum 50:1193-206. 2004
    ....
  40. ncbi Nonpeptide alpha V beta 3 antagonists. Part 9: Improved pharmacokinetic profile through the use of an aliphatic, des-amide backbone
    David B Whitman
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 14:4411-5. 2004
    ..Replacement of the lone amide bond with two methylene groups in this series yields more lipophilic compounds that have longer half-lives, lower clearance, and greater oral bioavailability when administered to dogs...
  41. ncbi Nonpeptide alpha V beta 3 antagonists. Part 10: In vitro and in vivo evaluation of a potent 7-methyl substituted tetrahydro-[1,8]naphthyridine derivative
    Michael J Breslin
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 14:4515-8. 2004
    ....
  42. ncbi Nonpeptide alphavbeta3 antagonists. Part 11: discovery and preclinical evaluation of potent alphavbeta3 antagonists for the prevention and treatment of osteoporosis
    Paul J Coleman
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Med Chem 47:4829-37. 2004
    ..On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis...
  43. doi The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K
    Jacques Yves Gauthier
    Merck Frosst Centre for Therapeutic Research, 16711 Transcanada Hwy, Kirkland, Que, Canada
    Bioorg Med Chem Lett 18:923-8. 2008
    ..Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors...
  44. ncbi Nonpeptide alpha(v)beta3 antagonists: identification of potent, chain-shortened 7-oxo RGD mimetics
    Amy E Zartman
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 15:1647-50. 2005
    ..Potent, novel 7-oxo alpha(v)beta3 antagonists have been prepared. These antagonists offer decreased plasma protein binding and excellent pharmacokinetic profiles...
  45. ncbi Mechanism of action of bisphosphonates
    Alfred A Reszka
    Department of Molecular Endocrinology and Bone Biology, Merck Research Laboratories, West Point, PA 19846, USA
    Curr Osteoporos Rep 1:45-52. 2003
    ..Although nitrogen-containing bisphosphonates can induce osteoclast apoptosis, this is not necessary for their inhibition of bone resorption...
  46. ncbi Nitrogen-containing bisphosphonate mechanism of action
    Alfred A Reszka
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486, USA
    Mini Rev Med Chem 4:711-9. 2004
    ..The occasional gastrointestinal irritation caused by N-BPs appears to be mechanism-based and is also briefly reviewed...
  47. ncbi Bisphosphonates and primary hyperparathyroidism
    Gideon A Rodan
    Department of Bone Biology and Osteoporosis Research, Merck and Co, West Point, Pennsylvania 19846, USA
    J Bone Miner Res 17:N150-3. 2002
    ..Limited, but convincing, data show that BPs at doses effective in osteoporosis also reverse bone loss associated with mild primary hyperparathyroidism (PHPT)...
  48. ncbi Non-peptide alpha(v)beta(3) antagonists. Part 3: identification of potent RGD mimetics incorporating novel beta-amino acids as aspartic acid replacements
    Paul J Coleman
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 12:31-4. 2002
    ..Modification of the beta-alanine 3-substituents alters the potency and physicochemical properties of these receptor antagonists and in some cases provides orally bioavailable alpha(v)beta(3) inhibitors...
  49. ncbi Non-peptide alpha(v)beta(3) antagonists. Part 5: identification of potent RGD mimetics incorporating 2-aryl beta-amino acids as aspartic acid replacements
    Karen M Brashear
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 12:3483-6. 2002
    ..A series of novel, highly potent alpha(v)beta(3) receptor antagonists with favorable pharmacokinetic profiles has been identified. In this series of antagonists, 2-aryl beta-amino acids function as potent aspartic acid replacements...
  50. ncbi Non-peptide alpha(v)beta(3) antagonists. Part 4: potent and orally bioavailable chain-shortened RGD mimetics
    Paul J Coleman
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 12:2463-5. 2002
    ..These chain-shortened alpha(v)beta(3) antagonists represent structurally novel integrin inhibitors...
  51. ncbi The development and function of the skeleton and bone metastases
    Gideon A Rodan
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Cancer 97:726-32. 2003
    ..Cells that participate in inflammation and immunity also can stimulate osteoclast formation and lead to bone destruction. Tumor cells most likely subvert these physiologic processes to lodge in bone and cause metastases...
  52. ncbi Bisphosphonate mechanism of action
    Alfred A Reszka
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, PA 19486, USA
    Curr Rheumatol Rep 5:65-74. 2003
    ..This mechanism is responsible for N-BP suppression of osteoclastic bone resorption and reduction of bone turnover, which leads to fracture prevention...
  53. ncbi Pathogenesis of osteoporosis
    Lawrence G Raisz
    Division of Endocrinology and Metabolism, Department of Medicine, University of Connecticut Health Center, 263 Farmington Avenue, MC 1850, Farmington, CT 06030 1850, USA raisznso uchc edu
    Endocrinol Metab Clin North Am 32:15-24. 2003
    ..Identification of specific pathogenetic mechanisms should lead to new approaches to the diagnosis and management of this disorder...
  54. ncbi Nonpeptide alpha(v)beta(3) antagonists. Part 2: constrained glycyl amides derived from the RGD tripeptide
    Robert S Meissner
    Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA
    Bioorg Med Chem Lett 12:25-9. 2002
    ..Further affinity increases were then achieved through the use of cyclic glycyl amide bond constraints...
  55. ncbi Osteoporosis and bisphosphonates
    Gideon A Rodan
    J Bone Joint Surg Am 85:8-12. 2003
  56. ncbi M-CSF induces the stable interaction of cFms with alphaVbeta3 integrin in osteoclasts
    Caryn L Elsegood
    Department of Molecular Endocrinology and Bone Biology, Merck Research Laboratories, West Point, PA 19486, USA
    Int J Biochem Cell Biol 38:1518-29. 2006
    ....
  57. ncbi Characterization of articular cartilage and subchondral bone changes in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis
    Tadashi Hayami
    Department Molecular Endocrinology and Bone Biology, Merck Res Labs, West Point, PA 19486, USA
    Bone 38:234-43. 2006
    ..Together, these findings support a role for bone remodeling in OA pathogenesis and suggest that these rat models are suitable for evaluating bone resorption inhibitors as potential disease-modifying pharmaco-therapies...
  58. ncbi IL-1 regulates cytoskeletal organization in osteoclasts via TNF receptor-associated factor 6/c-Src complex
    Ichiro Nakamura
    Department of Orthopedic Surgery, Faculty of Medicine, University of Tokyo, Tokyo, Japan
    J Immunol 168:5103-9. 2002
    ..Taken together, these data suggest that IL-1 signals feed into the tyrosine kinase pathways through a TRAF6-Src molecular complex, which regulates the cytoskeletal reorganization essential for osteoclast activation...
  59. ncbi Involvement of alpha(v)beta3 integrins in osteoclast function
    Ichiro Nakamura
    Department of Rheumatology, Yugawara Kosei Nenkin Hospital, 438 Miyakami, Yugawara, Ashigara shimo, Kanagawa 259 0314, Japan
    J Bone Miner Metab 25:337-44. 2007
    ....
  60. ncbi Estrogenic control of thermoregulation in ERalphaKO and ERbetaKO mice
    Evan E Opas
    Department of Molecular Endocrinology and Bone Biology, Merck Research Laboratories, West Point, PA 19486, USA
    Maturitas 53:210-6. 2006
    ..To elucidate the function of each estrogen receptor subtype control of thermoregulation, we developed an animal model demonstrating estrogen control of TST in mice...
  61. ncbi Mapping of MST1 kinase sites of phosphorylation. Activation and autophosphorylation
    Helmut Glantschnig
    Department of Bone Biology and Osteoporosis, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 277:42987-96. 2002
    ..Further activation of MST1 by caspase cleavage is best promoted by caspase-3, although this appears to be unnecessary for signaling and morphological responses...
  62. ncbi Distinct roles of p130Cas and c-Cbl in adhesion-induced or macrophage colony-stimulating factor-mediated signaling pathways in prefusion osteoclasts
    Ichiro Nakamura
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    Endocrinology 144:4739-41. 2003
    ..Taken together, p130Cas and c-Cbl play distinct roles in the signal transduction pathways that mediate cytoskeletal organization in osteoclasts...
  63. ncbi PYK2 autophosphorylation, but not kinase activity, is necessary for adhesion-induced association with c-Src, osteoclast spreading, and bone resorption
    Parvi T Lakkakorpi
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA
    J Biol Chem 278:11502-12. 2003
    ..We thus concluded that phosphorylation at Tyr-402 in PYK2 is essential in the regulation of adhesion-dependent cytoskeletal organization in osteoclasts...
  64. ncbi Rat tail skin temperature regulation by estrogen, phytoestrogens and tamoxifen
    Evan E Opas
    Merck Research Laboratories, Department of Molecular Endocrinology and Bone Biology, WP26A1000, West Point, PA 19486, USA
    Maturitas 48:463-71. 2004
    ..Develop a rat model for the evaluation of estrogenic agents on estrogen deficiency-induced changes in thermoregulation...
  65. ncbi The LATS2/KPM tumor suppressor is a negative regulator of the androgen receptor
    Mark Powzaniuk
    Department of Molecular Endocrinology, Merck Research Laboratories, West Point, Pennsylvania 19486 0004, USA
    Mol Endocrinol 18:2011-23. 2004
    ..The results suggest that LATS2 may play a role in AR-mediated transcription and contribute to the development of prostate cancer...
  66. ncbi Control of osteoblast function and regulation of bone mass
    Shun ichi Harada
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19002, USA
    Nature 423:349-55. 2003
    ..Recent advances, spearheaded by genetic information, offer the opportunity to stop or reverse this downhill course...
  67. doi Agonist-like SERM effects on ERalpha-mediated repression of MMP1 promoter activity predict in vivo effects on bone and uterus
    Angela Scafonas
    Molecular Endocrinology, Merck Research Laboratories, West Point, 770 Sumneytown Pike, PA 19486, USA
    J Steroid Biochem Mol Biol 110:197-206. 2008
    ..Together, these data suggest that estradiol and SERMs share common agonist transcriptional activity via protein-protein interactions at AP1...