Protein geranylgeranylation is required for osteoclast formation, function, and survival: Inhibition by bisphosphonates and GGTI-298

Journal of Bone and Mineral Research

Volumn 15, Issue 8, 2000, Pages 1467-1476

  Coxon, Fraser P ^a   Helfrich, Miep H ^a   Van't Hof, Robert ^a   Sebti, Saïd ^b   Ralston, Stuart H ^a   Hamilton, Andrew ^c   Rogers, Michael J ^a  

^a UNIVERSITY OF ABERDEEN   (United Kingdom)

^b H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^c UNIVERSITY OF PITTSBURGH   (United States)

Author keywords

Apoptosis; Bisphosphonate; Mevalonate; Osteoclast; Prenylation

Indexed keywords

ALENDRONIC ACID; BISPHOSPHONIC ACID DERIVATIVE; CLODRONIC ACID; ENZYME INHIBITOR; ETIDRONIC ACID; GERANYLTRANSFERASE; GGTI 298; IBANDRONIC ACID; MEVALONIC ACID; N [[5 [(2 AMINO 3 MERCAPTOPROPYL)AMINO][1,1' BIPHENYL] 2 YL]CARBONYL]METHIONINE METHYL ESTER; NITROGEN; PAMIDRONIC ACID; PROTEIN; RISEDRONIC ACID; TILUDRONIC ACID; ZOLEDRONIC ACID;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL FUNCTION; CELL SURVIVAL; CHICKEN; CONTROLLED STUDY; DRUG MECHANISM; EMBRYO; MOUSE; NEWBORN; NONHUMAN; OSTEOCLAST; OSTEOLYSIS; PRENYLATION; RABBIT;

EID: 0033930168     PISSN: 08840431     EISSN: None     Source Type: Journal    
DOI: 10.1359/jbmr.2000.15.8.1467     Document Type: Article

References (55)

1. Rogers MJ, Frith JC, Luckman SP, Coxon FP, Benford HL, Monkkonen J, Auriola S, Chilton KM, Russell RG 1999 Molecular mechanisms of action of bisphosphonates. Bone 24: 73S-79S.
2. Smith R, Russell RGG, Bishop M 1971 Diphosphonates and Paget's disease of bone. Lancet 1:945-947.
3. Fleisch H, Russell RGG, Francis MD 1969 Diphosphonates inhibit hydroxyapatite dissolution in vitro and bone resorption in tissue culture and in vivo. Science 165:1262-1264.
4. Shinoda H, Adamek G, Felix R, Fleisch H, Schenk R, Hagan P 1983 Structure-activity relationships of various bisphosphonates. Calcif Tiss Int 35:87-99.
5. Geddes AD, D'Souza SM, Ebetino FH, Ibbotson KJ 1994 Bisphosphonates: Structure-activity relationships and therapeutic implications In: Heersche JNM, Kanis JA, (eds.) Bone and Mineral Research. Elsevier Science BV Amsterdam, pp. 265-306.
6. Flanagan AM, Chambers TJ 1991 Inhibition of bone resorption by bisphosphonates: Interactions between bisphosphonates, osteoclasts, and bone. Calcif Tiss Int 49:407-415.
7. Murakami H, Takahashi N, Sasaki T, Udagawa N, Tanaka S, Nakamura I, Zhang D, Barbier A, Suda T 1995 A possible mechanism of the specific action of bisphosphonates on osteoclasts: tiludronate preferentially affects polarized osteoclasts having ruffled borders. Bone 17:137-144.
8. Sato M, Grasser W, Endo N, Akins R, Simmons H, Thompson DD, Golub E, Rodan GA 1991 Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest 88:2095-2105.
9. Zimolo Z, Wesolowski G, Rodan GA 1995 Acid extrusion is induced by osteoclast attachment to bone. Inhibition by alendronate and calcitonin. J Clin Invest 96:2277-2283.
10. Selander KS, Monkkonen J, Karhukorpi EK, Harkonen P, Hannuniemi R, Vaananen HK 1996 Characteristics of clodronate-induced apoptosis in osteoclasts and macrophages. Mol Pharmacol 50:1127-1138.
11. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Roodman GD, Mundy GR, Boyce BF 1995 Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo. J Bone Miner Res 10:1478-1487.
12. Boonekamp PM, van der Wee-Pals LJ, van Wijk-van Lennep MM, Thesing CW, Bijvoet OLM 1986 Two modes of action of bisphosphonates on osteoclastic resorption of mineralized matrix. Bone Miner 1:27-39.
13. Sahni M, Guenther HL, Fleisch H, Collin P, Martin TJ 1993 Bisphosphonates act on rat bone resorption through the mediation of osteoblasts. J Clin Invest 91:2004-2011.
14. Ebetino FH, Francis MD, Rogers MJ, Russell RGG 1998 Mechanisms of action of etidronate and other bisphosphonates. Rev Contemp Pharmacother 9:233-243.
15. Amin D, Cornell SA, Gustafson SK, Needle SJ, Ullrich JW, Bilder GE, Perrone MH 1992 Bisphosphonates used for the treatment of bone disorders inhibit squalene synthase and cholesterol biosynthesis. J Lipid Res 33:1657-1663.
16. Amin D, Cornell SA, Perrone MH, Bilder GE 1996 1-Hydroxy-3-(methylpentylamino)-propylidene-1, 1-bisphosphonic acid as a potent inhibitor of squalene synthase. Arzneimittelforschung 46:759-762.
17. Luckman SP, Hughes DE, Coxon FP, Russell RGG, Rogers MJ 1998 Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res 13: 581-589.
18. Luckman SP, Coxon FP, Ebetino FH, Russell RGG, Rogers MJ 1998 Heterocycle-containing bisphosphonates cause apoptosis and inhibit bone resorption by preventing protein prenylation: evidence from structure-activity relationships in J774 macrophages. J Bone Miner Res 13:1668-1678.
19. Clarke S 1992 Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. Annu Rev Biochem 61: 355 -86:355-386.
20. Clarke S 1992 Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. Annu Rev Biochem 61: 355 -86:355-386.
21. Gibbs JB, Oliff A 1997 The potential of famesyltransferase inhibitors as cancer chemotherapeutics. Annu Rev Pharmacol Toxicol 37:143-166.
22. Zhang FL, Casey PJ 1996 Protein prenylation: Molecular mechanisms and functional consequences. Annu Rev Biochem 65:241-269.
23. Casey PJ 1995 Protein lipidation in cell signaling. Science 268:221-225.
24. Seabra MC 1998 Membrane association and targeting of prenylated Ras-like GTPases. Cell Signal 10:167-172.
25. Fisher JE, Rogers MJ, Halasy JM, Luckman SP, Hughes DE, Masarachia PJ, Wesolowski G, Russell RGG, Rodan GA, Reszka AA 1999 Alendronate mechanism of action: Geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Proc Natl Acad Sci U S A 96:133-138.
26. van Beek E, Lowik C, Van der Pluijm G, Papapoulos S 1999 The role of geranylgeranylation in bone resorption and its suppression by bisphosphonates in fetal bone explants In vitro: A clue to the mechanism of action of nitrogen-containing bisphosphonates. J Bone Miner Res 14:722-729.
27. Lerner EC, Qian Y, Blaskovich MA, Fossum RD, Vogt A, Sun J, Cox AD, Der CJ, Hamilton AD, Sebti SM 1995 Ras CAAX peptidomimetic FTI-277 selectively blocks oncogenic Ras signaling by inducing cytoplasmic accumulation of inactive Ras-Raf complexes. J Biol Chem 270:26802-26806.
28. McGuire TF, Qian Y, Vogt A, Hamilton AD, Sebti SM 1996 Platelet-derived growth factor receptor tyrosine phosphorylation requires protein geranylgeranylation but not farnesylation. J Biol Chem 271:27402-27407.
29. Tezuka K, Sato T, Kamioka H, Nijweide PJ, Tanaka K, Matsuo T, Ohta M, Kurihara N, Hakeda Y, Kumegawa, M 1992 Identification of osteopontin in isolated rabbit osteoclasts. Biochem Biophys Res Commun 186:911-917.
30. 2 vitamin D3. Int J Exp Pathol 76:205-214.
31. Coxon FP, Benford HL, Russell RGG, Rogers MJ 1998 Protein synthesis is required for caspase activation and induction of apoptosis by bisphosphonate drugs. Mol Pharmacol 54: 631-638.
32. van't Hof RJ, Ralston SH 1997 Cytokine induced nitric oxide inhibits bone resorption by inducing apoptosis of osteoclast progenitors and suppressing osteoclast activity. J Bone Miner Res 12:1797-1804.
33. Turksen K, Kanehisa J, Opas M, Heersche JN, Aubin JE 1988 Adhesion patterns and cytoskeleton of rabbit osteoclasts on bone slices and glass. J Bone Miner Res 3:389-400.
34. Maltese WA, Sheridan KM, Repko EM, Erdman RA 1990 Post-translational modification of low molecular mass GTP-binding proteins by isoprenoid. J Biol Chem 265:2148-2155.
35. Wolda SL, Glomset JA 1988 Evidence for modification of lamin B by a product of mevalonic acid. J Biol Chem 263: 5997-6000.
36. Farnsworth CC, Wolda SL, Gelb MH, Glomset JA 1989 Human lamin B contains a famesylated cysteine residue. J Biol Chem 264:20422-20429.
37. Beck LA, Hosick TJ, Sinensky M 1988 Incorporation of a product of mevalonic acid metabolism into proteins of Chinese hamster ovary cell nuclei. J Cell Biol 107:1307-1316.
38. Casey PJ, Solski PA, Der CJ, Buss JE 1989 p21ras is modified by a farnesyl isoprenoid. Proc Natl Acad Sci USA 86:8323-8327.
39. Reiss Y, Goldstein JL, Seabra MC, Casey PJ, Brown MS 1990 Inhibition of purified p21ras farnesyl:protein transferase by Cys-AAX tetrapeptides. Cell 62:81-88.
40. Bergstrom JD, Bostedor RG, Masarachia PJ, Reszka AA, Rodan G 2000 alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase Arch Biochem Biophys 373: 231-241.
41. van Beek E, Pieterman E, Cohen Lowik C, Papapoulos S 1999 Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates. Biochem Biophys Res Commun 264:108-111.
42. Frith JC, Monkkonen J, Blackburn GM, Russell RGG, Rogers MJ 1997 Clodronate and liposome-encapsulated clodronate are metabolized to a toxic ATP analog, adenosine 5′-(β, γ-dichloromethylene) triphosphate, by mammalian cells in vitro. J Bone Miner Res 12:1358-1367.
43. Benford HL, Frith JC, Auriola S, Monkkonen J, Rogers MJ 1999 Farnesol and geranylgeraniol prevent activation of caspases by aminobisphosphonates: Biochemical evidence for two distinct pharmacological classes of bisphosphonate drugs. Mol Pharmacol 56:131-40.
44. Martin MB, Arnold W, Heath HT third, Urbina JA, Oldfield E 1999 Nitrogen-containing bisphosphonates as carbocation transition state analogs for isoprenoid biosynthesis. Biochem Biophys Res Commun 263:754-8.
45. Sato T, Morita I, Murota S 1998 Involvement of cholesterol in osteoclast-like cell formation via cellular fusion. Bone 23: 135-140.
46. Fan X, Biskobing DM, Bain S, Rubin J 1996 Ketoconazole and phorbol myristate acetate regulate osteoclast precursor fusion in primary murine marrow culture. J Bone Miner Res 11:1274-1280.
47. Stark WW, Jr., Blaskovich MA, Johnson BA, Qian Y, Vasudevan A, Pitt B, Hamilton AD, Sebti SM, Davies P 1998 Inhibiting geranylgeranylation blocks growth and promotes apoptosis in pulmonary vascular smooth muscle cells. Am J Physiol 275:L55-L63.
48. Miquel K, Pradines A, Sun J, Qian Y, Hamilton AD, Sebti SM, Favre G 1997 GGTI-298 induces G0-G1 block and apoptosis whereas FTI-277 causes G2-M enrichment in A549 cells. Cancer Res 57:1846-1850.
49. Vitale M, Di Matola T, Rossi G, Laezza C, Fenzi G, Bifulco M 1999 Prenyltransferase inhibitors induce apoptosis in proliferating thyroid cells through a p53-independent CrmA-sensitive, and caspase-3-like protease-dependent mechanism. Endocrinology 140:698-704.
50. Lakkakorpi P, Tuukkanen J, Hentunen T, Jarvelin K, Vaananen K 1989 Organization of osteoclast microfilaments during the attachment to bone surface in vitro. J Bone Miner Res 4:817-825.
51. Burgess TL, Qian Y, Kaufman S, Ring BD, Van G, Capparelli C, Kelley M, Hsu H, Boyle WJ, Dunstan CR, Hu S, Lacey DL 1999 The ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts. J Cell Biol 145:527-538.
52. Vogt A, Qian Y, McGuire TF, Hamilton AD, Sebti SM 1996 Protein geranylgeranylation, not farnesylation, is required for the G1 to S phase transition in mouse fibroblasts. Oncogene 13:1991-1999.
53. Hall A 1998 Rho GTPases and the actin cytoskeleton. Science 279:509-514.
54. Ridley AJ 1999 Rho family proteins and regulation of the actin cytoskeleton. Prog Mol Subcell Biol 22:1-22.
55. Zhang D, Udagawa N, Nakamura I, Murakami H, Saito S, Yamasaki K, Shibasaki Y, Morii N, Narumiya S, Takahashi N, Suda T. 1995 The small GTP-binding protein, rho p21, is involved in bone resorption by regulating cytoskeletal organization in osteoclasts. J Cell Sci 108:2285-2292.