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Regulation of Osteoclast Formation and Function*

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References

  1. Suda T, Nakamura I, Jimi E, Takahashi N. Regulation of osteoclast function. J Bone Miner Res 1997;12:869-879.

    Google Scholar 

  2. Roodman GD. Cell biology of the osteoclast. Exp Hematol 1999;27:1229-1241.

    Google Scholar 

  3. Väänänen HK, Zhao H, Mulari M, Halleen JM. The cell biology of osteoclast function. J Cell Sci 2000;113:377-381.

    Google Scholar 

  4. Rodan SB, Rodan GA. Integrin function in osteoclasts. J Endocrinol 1997;154:Suppl:S47-56.

    Google Scholar 

  5. Yoshida H, Hayashi S, Kunisada T, Ogawa M, Nishikawa S, Okamura H, Sudo T, Shultz LD. The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene. Nature 1990;345:442-444.

    Google Scholar 

  6. Cecchini MG, Hofstetter W, Halasy J, Wetterwald A, Felix R. Role of CSF-1 in bone and bone marrow development. Mol Reprod Dev 1997;46:75-83; discussion 83-74.

    Google Scholar 

  7. Suda T, Udagawa N, Nakamura I, Miyaura C, Takahashi N. Modulation of osteoclast differentiation by local factors. Bone 1995;17:87S-91S.

    Google Scholar 

  8. Chambers TJ, Owens JM, Hattersley G, Jat PS, Noble MD. Generation of osteoclast-inductive and osteoclastogenic cell lines from the H-2KbtsA58 transgenic mouse. Proc Natl Acad Sci USA 1993;90:5578-5582.

    Google Scholar 

  9. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Boyle WJ. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997;89:309-319.

    Google Scholar 

  10. Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 1998;139:1329-1337.

    Google Scholar 

  11. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS. Osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 1998;12:1260-1268.

    Google Scholar 

  12. Capparelli C, Kostenuik PJ, Morony S, Starnes C, Waimann B, Sarosi I, Lacey SL, Dunstan CR. Comparison of osteoprotegerin and pamidronate in a murine model of humoral hypercalcemia of malignancy. J Bone Miner Res 1999;14:(Suppl. 1):S163.

    Google Scholar 

  13. Bekker PJ, Holloway D, Nakanishi A, Arrighi HM, Dunstan CR. Osteoprotegrin (OPG) has potent and sustained anti-resorptive activity in postmenopausal women. J Bone Miner Res 1999;14(suppl. 1):S180.

    Google Scholar 

  14. Banks LM, Lees B, MacSweeney JE, Stevenson JC. Effect of degenerative spinal and aortic calcification on bone density measurements in post-menopausal women: links between osteoporosis and cardiovascular disease? Eur J Clin Invest 1994;24:813-817.

    Google Scholar 

  15. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 1998;93:165-176.

    Google Scholar 

  16. Wong BR, Josien R, Choi Y. TRANCE is a TNF family member that regulates dendritic cell and osteoclast function. J Leukoc Biol 1999;65:715-724.

    Google Scholar 

  17. 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.

    Google Scholar 

  18. Emery JG, McDonnell P, Burke MB, Deen KC, Lyn S, Silverman C, Dul E, Appelbaum ER, Eichman C, DiPrinzio R, Dodds RA, James IE, Rosenberg M, Lee JC, Young PR. Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem 1998;273:14363-14367.

    Google Scholar 

  19. Kong YY, Yoshida H, Sarosi I, Tan HL, Timms E, Capparelli C, Morony S, Oliveira-dos-Santos AJ, Van G, Itie A, Khoo W, Wakeham A, Dunstan CR, Lacey DL, Mak TW, Boyle WJ, Penninger JM. OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph-node organogenesis. Nature 1999;397:315-323.

    Google Scholar 

  20. Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, Tan HL, Elliott G, Kelley MJ, Sarosi I, Wang L, Xia XZ, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass MB, Boyle WJ. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA 1999;96:3540-3545.

    Google Scholar 

  21. Li J, Sarisu I, Yan X-Q, McCabe SM, Tan H-L, Capparelli C, Morony S, Elliot R, Van G, Kaufman S. Absolute requirement for the TNFR-related protein RANK during osteoclastogenesis and in regulation of bone mass and calcium metabolism. J Bone Miner Res 1999;14:(Suppl. 1):S149.

    Google Scholar 

  22. Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, Capparelli C, Kelley M, Hsu H, Boyle WJ, Dunstan CR, Hu S, Lacey DL. The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol 1999;145:527-538.

    Google Scholar 

  23. Arch RH, Gedrich RW, Thompson CB. Tumor necrosis factor receptor-associated factors (TRAFs)—a family of adapter proteins that regulates life and death. Genes Dev 1998;12:2821-2830.

    Google Scholar 

  24. Darnay BG, Haridas V, Ni J, Moore PA, Aggarwal BB. Characterization of the intracellular domain of receptor activator of NF-kappaB (RANK). Interaction with tumor necrosis factor receptor-associated factors and activation of NF-kappab and c-Jun N-terminal kinase. J Biol Chem 1998;273:20551-20555.

    Google Scholar 

  25. Wong BR, Josien R, Lee SY, Vologodskaia M, Steinman RM, Choi Y. The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor. J Biol Chem 1998;273 28355-28359.

    Google Scholar 

  26. Lomaga MA, Yeh WC, Sarosi I, Duncan GS, Furlonger C, Ho A, Morony S, Capparelli C, Van G, Kaufman S, van der Heiden A, Itie A, Wakeham A, Khoo W, Sasaki T, Cao Z, Penninger JM, Paige CJ, Lacey DL, Dunstan CR, Boyle WJ, Goeddel DV, Mak TW. TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 1999;13:1015-1024.

    Google Scholar 

  27. Naito A, Azuma S, Tanaka S, Miyazaki T, Takaki S, Takatsu K, Nakao K, Nakamura K, Katsuki M, Yamamoto T, Inoue J. Severe osteopetrosis, defective interleukin-1 signaling and lymph node organogenesis in TRAF6-deficient mice. Genes Cells 1999;4:353-362.

    Google Scholar 

  28. 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.

    Google Scholar 

  29. Lakkakorpi PT, Väänänen HK. Kinetics of the osteoclast cytoskeleton during the resorption cycle in vitro. J Bone Miner Res 1991;6:817-826.

    Google Scholar 

  30. Chambers TJ, Hall TJ. Cellular and molecular mechanisms in the regulation and function of osteoclasts. Vitam Horm 1991;46:41-86.

    Google Scholar 

  31. Nesbitt SA, Horton MA. Trafficking of matrix collagens through bone-resorbing osteoclasts. Science 1997;276:266-269.

    Google Scholar 

  32. Salo J, Lehenkari P, Mulari M, Metsikko K, Vaananen HK. Removal of osteoclast bone resorption products by transcytosis. Science 1997;276:270-273.

    Google Scholar 

  33. Marks SC, Jr. Osteoclast biology: Lessons from mammalian mutations. Am J Med Genet 1989;34:43-54.

    Google Scholar 

  34. Hynes RO. Cell adhesion: old and new questions. Trends Cell Biol 1999;9:M33-37.

    Google Scholar 

  35. Clark EA, Brugge JS. Integrins and signal transduction pathways: the road taken. Science 1995;268:233-239.

    Google Scholar 

  36. Wennerberg K, Lohikangas L, Gullberg D, Pfaff M, Johansson S, Fassler R. Beta 1 integrin-dependent and-independent polymerization of fibronectin. J Cell Biol 1996;132:227-238.

    Google Scholar 

  37. Wu C, Hughes PE, Ginsberg MH, McDonald JA. Identification of a new biological function for the integrin alpha v beta 3: Initiation of fibronectin matrix assembly. Cell Adhes Commun 1996;4:149-158.

    Google Scholar 

  38. Schlaepfer DD, Hauck CR, Sieg DJ. Signaling through focal adhesion kinase. Prog Biophys Mol Biol 1999;71:435-478.

    Google Scholar 

  39. Horton MA. The alpha v beta 3 integrin “vitronectin receptor”. Int J Biochem Cell Biol 1997;29:721-725.

    Google Scholar 

  40. Flores ME, Heinegard D, Reinholt FP, Andersson G. Bone sialoprotein coated on glass and plastic surfaces is recognized by different beta 3 integrins. Exp Cell Res 1996;227:40-46.

    Google Scholar 

  41. Helfrich MH, Nesbitt SA, Lakkakorpi PT, Barnes MJ, Bodary SC, Shankar G, Mason WT, Mendrick DL, Väänänen HK, Horton MA. Beta 1 integrins and osteoclast function: involvement in collagen recognition and bone resorption. Bone 1996;19:317-328.

    Google Scholar 

  42. Nakamura I, Takahashi N, Sasaki T, Jimi E, Kurokawa T, Suda T. Chemical and physical properties of the extracellular matrix are required for the actin ring formation in osteoclasts. J Bone Miner Res 1996;11:1873-1879.

    Google Scholar 

  43. Buckley CD, Doyonnas R, Newton JP, Blystone SD, Brown EJ, Watt SM, Simmons DL. Identification of alpha v beta 3 as a heterotypic ligand for CD31/PECAM-1. J Cell Sci 1996;109:437-445.

    Google Scholar 

  44. Ebeling O, Duczmal A, Aigner S, Geiger C, Schollhammer S, Kemshead JT, Moller P, Schwartz-Albiez R, Altevogt P. L1 adhesion molecule on human lymphocytes and monocytes: expression and involvement in binding to alpha v beta 3 integrin. Eur J Immunol 1996;26:2508-2516.

    Google Scholar 

  45. Wickham TJ, Mathias P, Cheresh DA, Nemerow GR. Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 1993;73:309-319.

    Google Scholar 

  46. Chambers TJ, Fuller K, Darby JA, Pringle JA, Horton MA. Monoclonal antibodies against osteoclasts inhibit bone resorption in vitro. Bone Miner 1986;1:127-135.

    Google Scholar 

  47. Horton MA, Taylor ML, Arnett TR, Helfrich MH. 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.

    Google Scholar 

  48. Sato M, Sardana MK, Grasser WA, Garsky VM, Murray JM, Gould RJ. Echistatin is a potent inhibitor of bone resorption in culture. J Cell Biol 1990;111:1713-1723.

    Google Scholar 

  49. Nakamura I, Pilkington MF, Lakkakorpi PT, Lipfert L, Sims SM, Dixon SJ, Rodan GA, Duong LT. Role of alpha v beta 3 integrin in osteoclast migration and formation of the sealing zone. J Cell Sci 1999;112:3985-3993.

    Google Scholar 

  50. Fisher JE, Caulfield MP, Sato M, Quartuccio HA, Gould RJ, Garsky VM, Rodan GA, Rosenblatt M. Inhibition of osteoclastic bone resorption in vivo by echistatin, an “arginyl-glycyl-aspartyl” (RGD)-containing protein. Endocrinology 1993;132:1411-1413.

    Google Scholar 

  51. King KL, D'Anza JJ, Bodary S, Pitti R, Siegel M, Lazarus RA, Dennis MS, Hammonds RG, Jr., Kukreja SC. Effects of kistrin on bone resorption in vitro and serum calcium in vivo. J Bone Miner Res 1994;9:381-387.

    Google Scholar 

  52. Masarachia P, Yamamoto M, Leu CT, Rodan G, Duong L. Histomorphometric evidence for echistatin inhibition of bone resorption in mice with secondary hyperparathyroidism. Endocrinology 1998;139:1401-1410.

    Google Scholar 

  53. Engleman VW, Nickols GA, Ross FP, Horton MA, Griggs DW, Settle SL, Ruminski PG, Teitelbaum SL. A peptidomimetic antagonist of the alpha(v)beta3 integrin inhibits bone resorption in vitro and prevents osteoporosis in vivo. J Clin Invest 1997;99:2284-2292.

    Google Scholar 

  54. Yamamoto M, Fisher JE, Gentile M, Seedor JG, Leu CT, Rodan SB, Rodan GA. The integrin ligand echistatin prevents bone loss in ovariectomized mice and rats. Endocrinology 1998;139:1411-1419.

    Google Scholar 

  55. Crippes BA, Engleman VW, Settle SL, Delarco J, Ornberg RL, Helfrich MH, Horton MA, Nickols GA. Antibody to beta3 integrin inhibits osteoclast-mediated bone resorption in the thyroparathyroidectomized rat. Endocrinology 1996;137:918-924.

    Google Scholar 

  56. McHugh KP, Hodival-Dilke K, Zheng M-H, Namba N, Lam J, Novack D, Fang X, Ross FP, Hynes R, Teitelbaum SL. Mice lacking beta 3 integrins are osteosclerotic due to dysfunctional osteoclasts. J Clin Invest 2000;433-440.

  57. Nesbitt S, Nesbit A, Helfrich M, Horton M. Biochemical characterization of human osteoclast integrins. Osteoclasts express alpha v beta 3, alpha 2 beta 1, and alpha v beta 1 integrins. J Biol Chem 1993;268:16737-16745.

    Google Scholar 

  58. Reinholt FP, Hultenby K, Oldberg A, Heinegard D. Osteopontin-a possible anchor of osteoclasts to bone. Proc Natl Acad Sci USA 1990;87:4473-4475.

    Google Scholar 

  59. Hultenby K, Reinholt FP, Heinegard D. Distribution of integrin subunits on rat metaphyseal osteoclasts and osteoblasts. Eur J Cell Biol 1993;62:86-93.

    Google Scholar 

  60. Lakkakorpi PT, Helfrich MH, Horton MA, Vaananen HK. Spatial organization of microfilaments and vitronectin receptor, alpha v beta 3, in osteoclasts. A study using confocal laser scanning microscopy. J Cell Sci 1993;104:663-670.

    Google Scholar 

  61. Paniccia R, Riccioni T, Zani BM, Zigrino P, Scotlandi K, Teti A. Calcitonin down-regulates immediate cell signals induced in human osteoclast-like cells by the bone sialoprotein-IIA fragment through a postintegrin receptor mechanism. Endocrinology 1995;136:1177-1186.

    Google Scholar 

  62. Zimolo Z, Wesolowski G, Tanaka H, Hyman JL, Hoyer JR, Rodan GA. Soluble alpha v beta 3-integrin ligands raise [Ca2+]i in rat osteoclasts and mouse-derived osteoclast-like cells. Am J Physiol 1994;266:C376-381.

    Google Scholar 

  63. Hruska KA, Rolnick F, Huskey M, Alvarez U, Cheresh D. Engagement of the osteoclast integrin alpha v beta 3 by osteopontin stimulates phosphatidylinositol 3-hydroxyl kinase activity. Ann NY Acad Sci 1995;760:151-165.

    Google Scholar 

  64. Lakkakorpi PT, Wesolowski G, Zimolo Z, Rodan GA, Rodan SB. Phosphatidylinositol 3-kinase association with the osteoclast cytoskeleton, and its involvement in osteoclast attachment and spreading. Exp Cell Res 1997;237:296-306.

    Google Scholar 

  65. Sato M, Bryant HU, Dodge JA, Davis H, Matter WF, Vlahos CJ. Effects of wortmannin analogs on bone in vitro and in vivo. J Pharmacol Exp Ther 1996;277:543-550.

    Google Scholar 

  66. Nakamura I, Takahashi N, Sasaki T, Tanaka S, Udagawa N, Murakami H, Kimura K, Kabuyama Y, Kurokawa T, Suda T, et al. Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption. FEBS Lett 1995; 361:79-84.

    Google Scholar 

  67. Chellaiah M, Fitzgerald C, Alvarez U, Hruska K. c-Src is required for stimulation of gelsolin-associated phosphatidylinositol 3-kinase. J Biol Chem 1998;273:11908-11916.

    Google Scholar 

  68. Duong LT, Lakkakorpi PT, Nakamura I, Machwate M, Nagy RM, Rodan GA. 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. J Clin Invest 1998; 102:881-892.

    Google Scholar 

  69. Nakamura I, Jimi E, Duong LT, Sasaki T, Takahashi N, Rodan GA, Suda T. Tyrosine phosphorylation of p130Cas is involved in actin organization in osteoclasts. J Biol Chem 1998;273:11144-11149.

    Google Scholar 

  70. Lakkakorpi PT, Nakamura I, Nagy RM, Parsons JT, Rodan GA, Duong LT. Stable association of PYK2 and p130Cas in osteoclasts and their co-localization in the sealing zone. J Biol Chem 1999;274:4900-4907.

    Google Scholar 

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Duong, L.T., Rodan, G.A. Regulation of Osteoclast Formation and Function*. Rev Endocr Metab Disord 2, 95–104 (2001). https://doi.org/10.1023/A:1010063225902

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