Osteoclast motility: Putting the brakes on bone resorption

Ageing Research Reviews

Volumn 10, Issue 1, 2011, Pages 54-61

  Novack, Deborah V ^a   Faccio, Roberta ^b  

^a Division of Bone and Mineral Diseases   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

v 3 integrin; M CSF; Migration; Podosome

Indexed keywords

1 [[6 (3 METHOXYESTRA 1,3,5(10) TRIEN 17BETA YL)AMINO]HEXYL] 1H PYRROLE 2,5 DIONE; ACTIN RELATED PROTEIN 2-3 COMPLEX; ARGINYLGLYCYLASPARTIC ACID; CATHEPSIN K; F ACTIN; FOCAL ADHESION KINASE 2; GROWTH FACTOR; GROWTH FACTOR M CSF; GUANINE NUCLEOTIDE EXCHANGE FACTOR; HISTONE DEACETYLASE 6; ITAM RECEPTOR; KILLER CELL ACTIVATING RECEPTOR ASSOCIATED PROTEIN; MEMBRANE RECEPTOR; NEUROFIBROMIN; OSTEOCLAST DIFFERENTIATION FACTOR; PHOSPHOLIPASE C GAMMA2; PHOSPHOLIPASE C INHIBITOR; PROTEIN CDC42; PROTEIN KINASE SYK; PROTEIN TYROSINE KINASE; PROTEIN VAV3; RAC PROTEIN; RHO KINASE; UNCLASSIFIED DRUG; VINCULIN; VITRONECTIN RECEPTOR; WISKOTT ALDRICH SYNDROME PROTEIN;

ACTIN FILAMENT; ACTIN POLYMERIZATION; BONE AGE; BONE MASS; CELL FUNCTION; CELL MEMBRANE; CELL MOTILITY; CYTOSKELETON; DRUG TARGETING; DWARFISM; FACE DYSMORPHIA; HUMAN; MEDIATOR; MOLECULE; NONHUMAN; OSTEOCLAST; OSTEOCLASTOGENESIS; OSTEOLYSIS; PODOSOME; PROTEIN FUNCTION; PROTEIN MOTIF; PYCNODYSOSTOSIS; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

ACTINS; ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; BONE AND BONES; BONE RESORPTION; CDC42 GTP-BINDING PROTEIN; CELL ADHESION; CELL DIFFERENTIATION; CELL MOVEMENT; CYTOSKELETON; HUMANS; INTEGRIN ALPHAVBETA3; MEMBRANE PROTEINS; OSTEOCLASTS; RANK LIGAND; SIGNAL TRANSDUCTION;

EID: 78650239453     PISSN: 15681637     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.arr.2009.09.005     Document Type: Review

References (92)

1. Arias-Salgado E.G., Lizano S., Sarkar S., Brugge J.S., Ginsberg M.H., Shattil S.J. Src kinase activation by direct interaction with the integrin β cytoplasmic domain. Proc. Natl. Acad. Sci. USA 2003, 100:13298-13302.
2. Armstrong A.P., Tometsko M.E., Glaccum M., Sutherland C.L., Cosman D., Dougall W.C. A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function. J. Biol. Chem. 2002, 277:44347-44356.
3. Boettiger D., Huber F., Lynch L., Blystone S. Activation of alpha(v)beta3-vitronectin binding is a multistage process in which increases in bond strength are dependent on Y747 and Y759 in the cytoplasmic domain of beta3. Mol. Biol. Cell 2001, 12:1227-1237.
4. Burgess T.L., Qian Y., Kaufman S., Ring B.D., Van G., Capparelli C., Kelley M., Hsu H., Boyle W.J., Dunstan C.R., Hu S., Lacey D.L. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J. Cell Biol. 1999, 145:527-538.
5. Calle Y., Jones G.E., Jagger C., Fuller K., Blundell M.P., Chow J., Chambers T., Thrasher A.J. WASp deficiency in mice results in failure to form osteoclast sealing zones and defects in bone resorption. Blood 2004, 103:3552-3561.
6. Chabadel A., Banon-Rodriguez I., Cluet D., Rudkin B.B., Wehrle-Haller B., Genot E., Jurdic P., Anton I.M., Saltel F. CD44 and beta3 integrin organize two functionally distinct actin-based domains in osteoclasts. Mol. Biol. Cell 2007, 18:4899-4910.
7. Chellaiah M.A. Regulation of actin ring formation by rho GTPases in osteoclasts. J. Biol. Chem. 2005, 280:32930-32943.
8. Chiusaroli R., Sanjay A., Henriksen K., Engsig M.T., Horne W.C., Gu H., Baron R. Deletion of the gene encoding c-Cbl alters the ability of osteoclasts to migrate, delaying resorption and ossification of cartilage during the development of long bones. Dev. Biol. 2003, 261:537-547.
9. Colonna M. TREMs in the immune system and beyond. Nat. Rev. Immunol. 2003, 3:445-453.
10. Coxon F.P., Taylor A. Vesicular trafficking in osteoclasts. Semin. Cell Dev. Biol. 2008, 19:424-433.
11. Destaing O., Saltel F., Geminard J.-C., Jurdic P., Bard F. Podosomes display actin turnover and dynamic self-organization in osteoclasts expressing actin-green fluorescent protein. Mol. Biol. Cell 2003, 14:407-416.
12. Destaing O., Saltel F., Gilquin B., Chabadel A., Khochbin S., Ory S., Jurdic P. A novel Rho-mDia2-HDAC6 pathway controls podosome patterning through microtubule acetylation in osteoclasts. J. Cell Sci. 2005, 118:2901-2911.
13. Destaing O., Sanjay A., Itzstein C., Horne W.C., Toomre D., De Camilli P., Baron R. The tyrosine kinase activity of c-Src regulates actin dynamics and organization of podosomes in osteoclasts. Mol. Biol. Cell 2008, 19:394-404.
14. Elsegood C.L., Zhuo Y., Wesolowski G.A., Hamilton J.A., Rodan G.A., Duong le T. M-CSF induces the stable interaction of cFms with alphaVbeta3 integrin in osteoclasts. Int. J. Biochem. Cell Biol. 2006, 38:1518-1529.
15. Epple H., Cremasco V., Zhang K., Mao D., Longmore G.D., Faccio R. Phospholipase Cgamma2 modulates integrin signaling in the osteoclast by affecting the localization and activation of Src kinase. Mol. Cell. Biol. 2008, 28:3610-3622.
16. Faccio R., Grano M., Colucci S., Villa A., Giannelli G., Quaranta V., Zallone A. Localization and possible role of two different αvβ3 integrin conformations in resting and resorbing osteoclasts. J. Cell Sci. 2002, 115:2919-2929.
17. Faccio R., Novack D.V., Zallone A., Ross F.P., Teitelbaum S.L. Dynamic changes in the osteoclast cytoskeleton in response to growth factors and cell attachment are controlled by β3 integrin. J. Cell Biol. 2003, 162:499-509.
18. Faccio R., Zou W., Colaianni G., Teitelbaum S.L., Ross F.P. High dose M-CSF partially rescues the Dap12-/- osteoclast phenotype. J. Cell. Biochem. 2003, 90:871-883.
19. Faccio R., Teitelbaum S.L., Fujikawa K., Chappel J., Zallone A., Tybulewicz V.L., Ross F.P., Swat W. Vav3 regulates osteoclast function and bone mass. Nat. Med. 2005, 11:284-290.
20. Faccio R., Takeshita S., Colaianni G., Chappel J.C., Zallone A., Teitelbaum S.L., Ross F.P. M-CSF regulates the cytoskeleton via recruitment of a multimeric signaling complex to c-Fms Tyr-Y559/697/721. J. Biol. Chem. 2007, 282:18991-18999.
21. Feng X., Novack D.V., Faccio R., Ory D.S., Aya K., Boyer M.I., McHugh K.P., Ross F.P., Teitelbaum S.L. A Glanzmann's mutation in β3 integrin specifically impairs osteoclast function. J. Clin. Invest. 2001, 107:1137-1144.
22. Fisher J.E., Caulfield M.P., Sato M., Quartuccio H.A., Gould R.J., Garsky V.M., Rodan G.A., Rosenblatt M. Inhibition of osteoclastic bone resorption in vivo by echistatin, an "arginyl-glycyl-aspartyl" (RGD)-containing protein. Endocrinology 1993, 132:1411-1413.
23. Frattini A., Orchard P.J., Sobacchi C., Giliani S., Abinun M., Mattsson J.P., Keeling D.J., Andersson A.K., Wallbrandt P., Zecca L., Notarangelo L.D., Vezzoni P., Villa A. Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Nat. Genet. 2000, 25:343-346.
24. Fukuda A., Hikita A., Wakeyama H., Akiyama T., Oda H., Nakamura K., Tanaka S. Regulation of osteoclast apoptosis and motility by small GTPase binding protein Rac1. J. Bone Miner. Res. 2005, 20:2245-2253.
25. Fuller K., Owens J.M., Jagger C.J., Wilson A., Moss R., Chambers T.J. Macrophage colony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts. J. Exp. Med. 1993, 178:1733-1744.
26. Gil-Henn H., Destaing O., Sims N.A., Aoki K., Alles N., Neff L., Sanjay A., Bruzzaniti A., De Camilli P., Baron R., Schlessinger J. Defective microtubule-dependent podosome organization in osteoclasts leads to increased bone density in Pyk2/mice. J. Cell Biol. 2007, 178:1053-1064.
27. Grey A., Chen Y., Paliwal I., Carlberg K., Insogna K. Evidence for a functional association between phosphatidylinositol 3-kinase and c-src in the spreading response of osteoclasts to colony-stimulating factor-1. Endocrinology 2000, 141:2129-2138.
28. Hakola H.P. Neuropsychiatric and genetic aspects of a new hereditary disease characterized by progressive dementia and lipomembranous polycystic osteodysplasia. Acta Psychiatr. Scand. Suppl. 1972, 232:1-173.
29. Honda S., Tomiyama Y., Pelletier A.J., Annis D., Honda Y., Orchekowski R., Ruggeri Z., Kunicki T.J. Topography of ligand-inducing binding sites, including a novel cation-sensitive epitope (AP5) at the amino terminus, of the human integrin β3 subunit. J. Biol. Chem. 1995, 270:11947-11954.
30. Horton M.A., Taylor M.L., Arnett T.R., Helfrich M.H. Arg-gly-asp (RGD) peptides and the anti-vitronectin receptor antibody 23C6 inhibit dentine resorption and cell spreading by osteoclasts. Exp. Cell Res. 1991, 195:368-375.
31. Horton M.A., Massey H.M., Rosenberg N., Nicholls B., Seligsohn U., Flanagan A.M. Upregulation of osteoclast α2β1 integrin compensates for lack of αvβ3 vitronectin receptor in Iraqi-Jewish-type Glanzmann thrombasthenia. Br. J. Haematol. 2003, 122:950-957.
32. Hunt N.P., Cunningham S.J., Adnan N., Harris M. The dental, craniofacial, and biochemical features of pyknodysostosis: a report of three new cases. J. Oral Maxillofac. Surg. 1998, 56:497-504.
33. Hurst I.R., Zuo J., Jiang J., Holliday L.S. Actin-related protein 2/3 complex is required for actin ring formation. J. Bone Miner. Res. 2004, 19:499-506.
34. Ikeda A., Chang K.T., Matsumoto Y., Furuhata Y., Nishihara M., Sasaki F., Takahashi M. Obesity and insulin resistance in human growth hormone transgenic rats. Endocrinology 1998, 139:3057-3063.
35. Ikeda F., Nishimura R., Matsubara T., Tanaka S., Inoue J., Reddy S.V., Hata K., Yamashita K., Hiraga T., Watanabe T., Kukita T., Yoshioka K., Rao A., Yoneda T. Critical roles of c-Jun signaling in regulation of NFAT family and RANKL-regulated osteoclast differentiation. J. Clin. Invest. 2004, 114:475-484.
36. Insogna K.L., Sahni M., Grey A.B., Tanaka S., Horne W.C., Neff L., Mitnick M., Levy J.B., Baron R. Colony-stimulating factor-1 induces cytoskeletal reorganization and c-src-dependent tyrosine phosphorylation of selected cellular proteins in rodent osteoclasts. J. Clin. Invest. 1997, 100:2476-2485.
37. Ito Y., Zheng Y., Johnson J.F., Yang L., Teitelbaum S.L., Ross F.P., Zhao H. The small GTPase cdc42 enhances osteoclastogenesis and bone resorption. J. Bone Miner. Res. 2007, 22:S42.
38. Jakus Z., Fodor S., Abram C.L., Lowell C.A., Mocsai A. Immunoreceptor-like signaling by beta 2 and beta 3 integrins. Trends Cell Biol. 2007, 17:493-501.
39. Jones G.E., Zicha D., Dunn G.A., Blundell M., Thrasher A. Restoration of podosomes and chemotaxis in Wiskott-Aldrich syndrome macrophages following induced expression of WASp. Int. J. Biochem. Cell Biol. 2002, 34:806-815.
40. Jones G.E., Prigmore E., Calvez R., Hogan C., Dunn G.A., Hirsch E., Wymann M.P., Ridley A.J. Requirement for PI 3-kinase [gamma] in macrophage migration to MCP-1 and CSF-1. Exp. Cell Res. 2003, 290:120-131.
41. Jurdic P., Saltel F., Chabadel A., Destaing O. Podosome and sealing zone: specificity of the osteoclast model. Eur. J. Cell Biol. 2006, 85:195-202.
42. Kaifu T., Nakahara J., Inui M., Mishima K., Momiyama T., Kaji M., Sugahara A., Koito H., Ujike-Asai A., Nakamura A., Kanazawa K., Tan-Takeuchi K., Iwasaki K., Yokoyama W.M., Kudo A., Fujiwara M., Asou H., Takai T. Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in DAP12-deficient mice. J. Clin. Invest. 2003, 111:323-332.
43. Kim H., Choi H.K., Shin J.H., Kim K.H., Huh J.Y., Lee S.A., Ko C.Y., Kim H.S., Shin H.I., Lee H.J., Jeong D., Kim N., Choi Y., Lee S.Y. Selective inhibition of RANK blocks osteoclast maturation and function and prevents bone loss in mice. J. Clin. Invest. 2009, 119:813-825.
44. Kim K., Lee S.H., Kim J.H., Choi Y., Kim N. NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and DC-STAMP. Mol. Endocrinol. 2008, 22:176-185.
45. Koga T., Inui M., Inoue K., Kim S., Suematsu A., Kobayashi E., Iwata T., Ohnishi H., Matozaki T., Kodama T., Taniguchi T., Takayanagi H., Takai T. Costimulatory signals mediated by the ITAM motif cooperate with RANKL for bone homeostasis. Nature 2004, 428:758-763.
46. Kondo T., Takahashi K., Kohara N., Takahashi Y., Hayashi S., Takahashi H., Matsuo H., Yamazaki M., Inoue K., Miyamoto K., Yamamura T. Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms. Neurology 2002, 59:1105-1107.
47. Kornak U., Kasper D., Bosl M.R., Kaiser E., Schweizer M., Schulz A., Friedrich W., Delling G., Jentsch T.J. Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell 2001, 104:205-215.
48. Lacey D.L., Timms E., Tan H.L., Kelley M.J., Dunstan C.R., Burgess T., Elliott R., Colombero A., Elliott G., Scully S., Hsu H., Sullivan J., Hawkins N., Davy E., Capparelli C., Eli A., Qian Y.X., Kaufman S., Sarosi I., Shalhoub V., Senaldi G., Guo J., Delaney J., Boyle W.J. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998, 93:165-176.
49. Lakkakorpi P.T., Bett A.J., Lipfert L., Rodan G.A., Duong L.T. PYK2 autophosphorylation, but not kinase activity, is necessary for adhesion-induced association with c-Src, osteoclast spreading, and bone resorption. J. Biol. Chem. 2003, 278:11502-11512.
50. Lanier L.L., Bakker A.B.H. The ITAM-bearing transmembrane adaptor DAP12 in lymphoid and myeloid cell function. Immunol. Today 2000, 21:611-614.
51. Linder M.E., Deschenes R.J. Palmitoylation: policing protein stability and traffic. Nat. Rev. Mol. Cell. Biol. 2007, 8:74-84.
52. Linder S., Nelson D., Weiss M., Aepfelbacher M. Wiskott-Aldrich syndrome protein regulates podosomes in primary human macrophages. Proc. Natl. Acad. Sci. USA 1999, 96:9648-9653.
53. Linder S., Aepfelbacher M. Podosomes: adhesion hot-spots of invasive cells. Trends Cell Biol. 2003, 13:376-385.
54. Luxenburg C., Geblinger D., Klein E., Anderson K., Hanein D., Geiger B., Addadi L. The architecture of the adhesive apparatus of cultured osteoclasts: from podosome formation to sealing zone assembly. PLoS ONE 2007, 2:e179.
55. Maa M.C., Wilson L.K., Moyers J.S., Vines R.R., Parsons J.T., Parsons S.J. Identification and characterization of a cytoskeleton-associated, epidermal growth factor sensitive pp60c-src substrate. Oncogene 1992, 7:2429-2438.
56. Mao D., Epple H., Uthgenannt B., Novack D.V., Faccio R. PLCγ2 regulates osteoclastogenesis via its interaction with ITAM proteins and GAB2. J. Clin. Invest. 2006, 116:2869-2879.
57. Marchisio P.C., Bergui L., Corbascio G.C., Cremona O., D'Urso N., Schena M., Tesio L., Caligaris-Cappio F. Vinculin, talin, and integrins and localized at specific adhesion sites of malignant B lymphocytes. Blood 1988, 72:830-833.
58. Matsuyama A., Shimazu T., Sumida Y., Saito A., Yoshimatsu Y., Seigneurin-Berny D., Osada H., Komatsu Y., Nishino N., Khochbin S., Horinouchi S., Yoshida M. In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. EMBO J. 2002, 21:6820-6831.
59. McHugh K.P., Hodivala-Dilke K., Zheng M.H., Namba N., Lam J., Novack D., Feng X., Ross F.P., Hynes R.O., Teitelbaum S.L. Mice lacking β3 integrins are osteosclerotic because of dysfunctional osteoclasts. J. Clin. Invest. 2000, 105:433-440.
60. McVicar D.W., Taylor L.S., Gosselin P., Willette-Brown J., Mikhael A.I., Geahlen R.L., Nakamura M.C., Linnemeyer P., Seaman W.E., Anderson S.K., Ortaldo J.R., Mason L.H. DAP12-mediated signal transduction in natural killer cells. A dominant role for the Syk protein-tyrosine kinase. J. Biol. Chem. 1998, 273:32934-32942.
61. Mocsai A., Humphrey M.B., Van Ziffle J.A., Hu Y., Burghardt A., Spusta S.C., Majumdar S., Lanier L.L., Lowell C.A., Nakamura M.C. The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional osteoclasts through the Syk tyrosine kinase. Proc. Natl. Acad. Sci. USA 2004, 101:6158-6163.
62. Nakamura I., Lipfert L., Rodan G.A., Duong L.T. Convergence of αvβ3 integrin- and macrophage colony stimulating factor-mediated signals on phospholipase Cgamma in prefusion ostelclasts. J. Cell Biol. 2001, 152:361-373.
63. Novack D.V., Teitelbaum S.L. The osteoclast: friend or foe?. Annu. Rev. Pathol. 2008, 3:457-484.
64. Pfaff M., Jurdic P. Podosomes in osteoclast-like cells: structural analysis and cooperative roles of paxillin, proline-rich tyrosine kinase 2 (Pyk2) and integrin αvβ3. J. Cell Sci. 2001, 114:2775-2786.
65. Pixley F.J., Stanley E.R. CSF-1 regulation of the wandering macrophage: complexity in action. Trends Cell Biol. 2004, 14:628-638.
66. Qin J., Vinogradova O., Plow E.F. Integrin bidirectional signaling: a molecular view. PLoS Biol. 2004, 2:726-729.
67. Ridley A.J., Schwartz M.A., Burridge K., Firtel R.A., Ginsberg M.H., Borisy G., Parsons J.T., Horwitz A.R. Cell migration: integrating signals from front to back. Science 2003, 302:1704-1709.
68. Rohatgi R., Ma L., Miki H., Lopez M., Kirchhausen T., Takenawa T., Kirschner M.W. The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly. Cell 1999, 97:221-231.
69. Ross F.P., Teitelbaum S.L. αvβ3 and macrophage colony-stimulating factor: partners in osteoclast biology. Immunol. Rev. 2005, 208:88-105.
70. Saftig P., Hunziker E., Wehmeyer O., Jones S., Boyde A., Rommerskirch W., Moritz J.D., Schu P., von Figura K. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc. Natl. Acad. Sci. USA 1998, 95:13453-13458.
71. Saltel F., Chabadel A., Bonnelye E., Jurdic P. Actin cytoskeletal organisation in osteoclasts: a model to decipher transmigration and matrix degradation. Eur. J. Cell Biol. 2008, 87:459-468.
72. Sanjay A., Houghton A., Neff L., DiDomenico E., Bardelay C., Antoine E., Levy J., Gailit J., Bowtell D., Horne W.C., Baron R. Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta(3) integrin-mediated signaling, cell adhesion, and osteoclast motility. J. Cell Biol. 2001, 152:181-195.
73. Soriano P., Montgomery C., Geske R., Bradley A. Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell 1991, 64:693-702.
74. Sun Y., Buki K.G., Ettala O., Vaaraniemi J.P., Vaananen H.K. Possible role of direct Rac1-Rab7 interaction in ruffled border formation of osteoclasts. J. Biol. Chem. 2005, 280:32356-32361.
75. Takagi J., Petre B., Walz T., Springer T. Global conformational rearrangements in integrin extracellular domains in outside-in and inside-out signaling. Cell 2002, 110:599-611.
76. Tehrani S., Faccio R., Chandrasekar I., Ross F.P., Cooper J.A. Cortactin has an essential and specific role in osteoclast actin assembly. Mol. Biol. Cell 2006, 17:2882-2895.
77. Tomasello E., Olcese L., Vely F., Geourgeon C., Blery M., Moqrich A., Gautheret D., Djabali M., Mattei M.-G., Vivier E. Gene structure, expression pattern, and biological activity of mouse killer cell activating receptor-associated protein (KARAP)/DAP-12. J. Biol. Chem. 1998, 273:34115-34119.
78. Tsurukai T., Udagawa N., Matsuzaki K., Takahashi N., Suda T. Roles of macrophage-colony stimulating factor and osteoclast differentiation factor in osteoclastogenesis. J. Bone Miner. Metab. 2000, 18:177-184.
79. Vaira S., Alhawagri M., Anwisye I., Kitaura H., Faccio R., Novack D.V. RelA/p65 promotes osteoclast differentiation by blocking a RANKL-induced apoptotic JNK pathway in mice. J. Clin. Invest. 2008, 118:2088-2097.
80. Vaira S., Johnson T., Hirbe A.C., Alhawagri M., Anwisye I., Sammut B., O'Neal J., Zou W., Weilbaecher K.N., Faccio R., Novack D.V. RelB is the NF-kappaB subunit downstream of NIK responsible for osteoclast differentiation. Proc. Natl. Acad. Sci. USA 2008, 105:3897-3902.
81. Wang Y., Lebowitz D., Sun C., Thang H., Grynpas M.D., Glogauer M. Identifying the relative contributions of Rac1 and Rac2 to osteoclastogenesis. J. Bone Miner. Res. 2008, 23:260-270.
82. Wells C.M., Walmsley M., Ooi S., Tybulewicz V., Ridley A.J. Rac1-deficient macrophages exhibit defects in cell spreading and membrane ruffling but not migration. J. Cell Sci. 2004, 117:1259-1268.
83. Yagi M., Miyamoto T., Sawatani Y., Iwamoto K., Hosogane N., Fujita N., Morita K., Ninomiya K., Suzuki T., Miyamoto K., Oike Y., Takeya M., Toyama Y., Suda T. DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells. J. Exp. Med. 2005, 202:345-351.
84. Yagi M., Ninomiya K., Fujita N., Suzuki T., Iwasaki R., Morita K., Hosogane N., Matsuo K., Toyama Y., Suda T., Miyamoto T. Induction of DC-STAMP by alternative activation and downstream signaling mechanisms. J. Bone Miner. Res. 2007, 22:992-1001.
85. Yamauchi A., Kim C., Li S., Marchal C.C., Towe J., Atkinson S.J., Dinauer M.C. Rac2-deficient murine macrophages have selective defects in superoxide production and phagocytosis of opsonized particles. J. Immunol. 2004, 173:5971-5979.
86. Yan J., Chen S., Zhang Y., Li X., Li Y., Wu X., Yuan J., Robling A.G., Kapur R., Chan R.J., Yang F.C. Rac1 mediates the osteoclast gains-in-function induced by haploinsufficiency of Nf1. Hum. Mol. Genet. 2008, 17:936-948.
87. Yarali N., Fisgin T., Duru F., Kara A. Osteopetrosis and Glanzmann's thrombasthenia in a child. Ann. Hematol. 2003, 82:254-256.
88. Yasuda H., Shima N., Nakagawa N., Yamaguchi K., Kinosaki M., Mochizuki S., Tomoyasu A., Yano K., Goto M., Murakami A., Tsuda E., Morinaga T., Higashio K., Udagawa N., Takahashi N., Suda T. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc. Natl. Acad. Sci. USA 1998, 95:3597-3602.
89. Yeatman T.J. A renaissance for SRC. Nat. Rev. Cancer 2004, 4:470-480.
90. Zambonin-Zallone A., Teti A., Grano M., Rubinacci A., Abbadini M., Gaboli M., Marchisio P.C. Immunocytochemical distribution of extracellular matrix receptors in human osteoclasts: a β3 integrin is colocalized with vinculin and talin in the podosomes of osteoclastoma giant cells. Exp. Cell Res. 1989, 182:645-652.
91. Zou W., Kitaura H., Reeve J., Long F., Tybulewicz V.L.J., Shattil S.J., Ginsberg M.H., Ross F.P., Teitelbaum S.L. Syk, c-Src, the αvβ3 integrin, and ITAM immunoreceptors, in concert, regulate osteoclastic bone resorption. J. Cell Biol. 2007, 176:877-888.
92. Zou W., Reeve J.L., Liu Y., Teitelbaum S.L., Ross F.P. DAP12 couples c-Fms activation to the osteoclast cytoskeleton by recruitment of Syk. Mol. Cell 2008, 31:422-431.