DOI: 10.1359/jbmr.1997.12.7.1116. Specific Inhibitors of Vacuolar H+-ATPase Trigger Apoptotic Cell Death of Osteoclasts

Specific Inhibitors of Vacuolar H+-ATPase Trigger Apoptotic Cell Death of Osteoclasts

10.1359/jbmr.1997.12.7.1116

Crossref journal-article

Oxford University Press (OUP)

Journal of Bone and Mineral Research (286)

Abstract

Abstract Osteoclasts are multinucleated bone-resorbing cells that play a critical role in bone remodeling. Specific inhibitors of vacuolar H+-ATPase (V-ATPase), concanamycin A and bafilomycin A1, abolish bone resorption by osteoclasts. In this study, we examined whether these V-ATPase inhibitors trigger apoptotic cell death in osteoclasts, using murine osteoclast-like multinucleated cells (OCLs) formed in vitro. Acridine orange staining revealed that the treatment of OCLs with concanamycin A resulted in chromatin condensation and alterations in nuclear morphology within a few hours. The TdT-mediated dUTP-nick-end labeling (TUNEL) reaction confirmed the apoptotic features of OCLs treated with concanamycin A. The accelerated apoptotic cell death induced by concanamycin A occurred in OCLs treated with interleukin-1α or macrophage colony-stimulating factor as well, which are known to elongate the survival time of osteoclasts. In contrast, these inhibitors did not induce cell death of osteoblastic cells isolated from mouse calvaria. These results suggest that functional impairment of V-ATPase triggers apoptotic cell death in osteoclasts.

Bibliography

Okahashi, N., Nakamura, I., Jimi, E., Koide, M., Suda, T., & Nishihara, T. (1997). Specific Inhibitors of Vacuolar H+-ATPase Trigger Apoptotic Cell Death of Osteoclasts. Journal of Bone and Mineral Research, 12(7), 1116â1123.

Authors 6

Nobuo Okahashi (first)
Ichiro Nakamura (additional)
Eijiro Jimi (additional)
Masanori Koide (additional)
Tatsuo Suda (additional)
Tatsuji Nishihara (additional)

References 41 Referenced 57

{'key': '2024020713225312800_bib1', 'first-page': '266', 'article-title': 'Modulation of osteoclast differentiation: Update 1995', 'volume': '4', 'author': 'Suda', 'year': '1995', 'journal-title': 'Endocr Rev'} / Endocr Rev / Modulation of osteoclast differentiation: Update 1995 by Suda (1995)
10.1242/jcs.66.1.383 / J Cell Sci / Resorption of bone by isolated rabbit osteoclasts by Chambers (1984)
10.1083/jcb.101.6.2210 / J Cell Biol / Cell-mediated extracellular acidification and bone resorption: Evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border by Baron (1985)
10.1083/jcb.102.4.1164 / J Cell Biol / Isolated osteoclasts resorb the organic and inorganic components of bone by Blair (1986)
10.1126/science.2528207 / Science / Osteoclastic bone respoption by a polarized vacuolar proton pump by Blair (1989)
10.1083/jcb.111.3.1305 / J Cell Biol / Evidence for the presence of a proton pump of the vacuolar H+-ATPase type in the ruffled borders of osteoclasts by Väänänen (1990)
10.1016/S0021-9258(18)51486-1 / J Biol Chem / H+-translocating ATPase in Golgi apparatus: Characterization as vacuolar H+-ATPase and its subunit structures by Moriyama (1989)
10.1016/0968-0004(89)90134-5 / Trends Biol Sci / The evolution of H+-ATPases by Nelson (1989)
10.1152/physrev.1989.69.3.765 / Physiol Rev / Structure and function of vacuolar class of ATP-driven proton pumps by Forgac (1989)
10.1021/bi00066a008 / Biochemistry / Inhibitory effect of modified bafilomycins and concanamycins on P- and V-type adenosinetriphosphatases by Dröse (1993)
10.1111/j.1432-1033.1992.tb17061.x / Eur J Biochem / Inhibition of the acidification of endosomes and lysosomes by the antibiotic concanamycin B in macrophage J774 by Woo (1992)
10.1073/pnas.85.21.7972 / Proc Natl Acad Sci USA / Bafilomycins: A class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells by Bowman (1988)
10.1016/S0021-9258(18)45829-2 / J Biol Chem / The cytotoxic action of diphtheria toxin and its degradation in intact vero cells are inhibited by bafilomycin A1, a specific inhibitor of vacuolar-type H+-ATPase by Umata (1990)
10.1016/0006-291X(90)91709-2 / Biochem Biophys Res Commun / Inhibition of osteoclast proton transport by bafilomycin A1 abolishes bone resorption by Sundquist (1990)
{'key': '2024020713225312800_bib15', 'first-page': '265', 'article-title': 'Expression of vacuolar H+-ATPase in osteoclasts and its role in resorption', 'volume': '278', 'author': 'Sasaki', 'year': '1994', 'journal-title': 'Cell Tissue Res'} / Cell Tissue Res / Expression of vacuolar H+-ATPase in osteoclasts and its role in resorption by Sasaki (1994)
10.1002/jcp.1041570303 / J Cell Physiol / Inhibitors of vacuolar-type H+-ATPase suppresses proliferation of cultured cells by Manabe (1993)
10.1210/endo-123-5-2600 / Endocrinology / Induction of calcitonin receptors by 1α,25-dihydroxyvitamin D3 in osteoclast-like multinucleated cells formed from mouse bone marrow cells by Takahashi (1988)
10.1002/jbmr.5650071109 / J Bone Miner Res / Preparation and characterization of a mouse osteoclast-like multinucleated cell population by Akatsu (1992)
10.1016/0014-5793(95)00153-Z / FEBS Lett / Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption by Nakamura (1995)
10.1074/jbc.271.9.4605 / J Biol Chem / Interleukin-1α activates an NF-κB-like factor in osteoclast-like cells by Jimi (1996)
10.1210/endo.136.2.7835314 / Endocrinology / Macrophage colony-stimulating factor and interleukin-1α maintain the survival of osteoclast-like cells by Jimi (1995)
10.1016/0022-1759(83)90303-4 / J Immunol Meth / Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays by Mossmann (1983)
10.1084/jem.178.5.1733 / J Exp Med / Macrophage colony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts by Fuller (1993)
10.1083/jcb.119.3.493 / J Cell Biol / Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation by Gavrieli (1992)
10.1038/356397a0 / Nature / Social controls on cell survival and cell death by Raff (1992)
10.1016/0167-5699(93)90214-6 / Immunol Today / Apoptosis by Cohen (1993)
10.1002/jbmr.5650110203 / J Bone Miner Res / A new model for the regulation of bone resorption, with particular reference to the effects of bisphosphonates by Parfitt (1996)
{'issue': 'Suppl 1', 'key': '2024020713225312800_bib28', 'first-page': 'S174', 'article-title': 'Osteoclasts undergo apoptosis at the interface between resorption and formation in bone remodelling units', 'volume': '9', 'author': 'Wright', 'year': '1994', 'journal-title': 'J Bone Miner Res'} / J Bone Miner Res / Osteoclasts undergo apoptosis at the interface between resorption and formation in bone remodelling units by Wright (1994)
10.1038/306378a0 / Nature / An interleukin 1 like factor stimulates bone resorption in vitro by Gowen (1983)
10.4049/jimmunol.136.7.2478 / J Immunol / Actions of recombinant interleukin 1, interleukin 2, and interferon-γ on bone resorption in vitro by Gowen (1986)
10.1038/345442a0 / Nature / The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene by Yoshida (1990)
10.1016/0005-2736(95)00285-5 / Biochim Biophys Acta / [3H]Bafilomycin as a probe for the transmembrane proton channel of the osteoclast vacuolar H+-ATPase by Mattsson (1996)
10.1002/jbmr.5650101008 / J Bone Miner Res / Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo by Hughes (1995)
10.1016/S0021-9258(19)39163-X / J Biol Chem / A vacuolar type H+-ATPase regulates cytoplasmic pH in murine macrophages by Swallow (1990)
10.1016/0006-291X(92)90814-2 / Biochem Biophys Res Commun / Endonuclease activation during apoptosis: The role of cytosolic Ca2+ and pH by Barry (1992)
10.1073/pnas.92.13.5965 / Proc Natl Acad Sci USA / Cell acidification in apoptosis: Granulocyte colony-stimulating factor delays programed cell death in neutrophils by up-regulating the vacuolar H+-ATPase by Gottlieb (1995)
10.1074/jbc.270.7.3203 / J Biol Chem / Apoptosis in an interleukin-2-dependent cytotoxic T lymphocyte cell line is associated with intracellular acidification: Role of the Na+/H+-antiport by Li (1995)
10.1074/jbc.270.11.6235 / J Biol Chem / Intracellular alkalinization suppresses lovastatin-induced apoptosis in HL-60 cells through the inactivation of a pH-dependent endonuclease by Perez-Sala (1995)
10.1006/bbrc.1995.1964 / Biochem Biophys Res Commun / Specific inhibitors of vacuolar type H+-ATPases induce apoptotic cell death by Nishihara (1995)
10.1111/j.1600-065X.1994.tb00886.x / Immunol Rev / Analysis of the role of bcl-2 in apoptosis by Hawkins (1994)
10.1074/jbc.271.27.16260 / J Biol Chem / Evidents in apoptosis: Acidification is downstream of protease activation and bcl-2 protection by Meisenholder (1996)

Dates

Type	When
Created	19 years, 4 months ago (April 26, 2006, 6:03 p.m.)
Deposited	1 year, 5 months ago (March 13, 2024, 10:55 a.m.)
Indexed	4 months, 2 weeks ago (April 16, 2025, 12:28 p.m.)
Issued	28 years, 2 months ago (July 1, 1997)
Published	28 years, 2 months ago (July 1, 1997)
Published Online	15 years, 8 months ago (Dec. 4, 2009)
Published Print	28 years, 2 months ago (July 1, 1997)

Funders 0

None

BibTeX

@article{Okahashi_1997, title={Specific Inhibitors of Vacuolar H+-ATPase Trigger Apoptotic Cell Death of Osteoclasts}, volume={12}, ISSN={1523-4681}, url={http://dx.doi.org/10.1359/jbmr.1997.12.7.1116}, DOI={10.1359/jbmr.1997.12.7.1116}, number={7}, journal={Journal of Bone and Mineral Research}, publisher={Oxford University Press (OUP)}, author={Okahashi, Nobuo and Nakamura, Ichiro and Jimi, Eijiro and Koide, Masanori and Suda, Tatsuo and Nishihara, Tatsuji}, year={1997}, month=jul, pages={1116–1123} }

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      "article-title": "Modulation of osteoclast differentiation: Update 1995",
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      "author": "Suda",
      "year": "1995",
      "journal-title": "Endocr Rev"
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      "first-page": "383",
      "DOI": "10.1242/jcs.66.1.383",
      "article-title": "Resorption of bone by isolated rabbit osteoclasts",
      "volume": "66",
      "author": "Chambers",
      "year": "1984",
      "journal-title": "J Cell Sci"
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      "first-page": "2210",
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      "article-title": "Cell-mediated extracellular acidification and bone resorption: Evidence for a low pH in resorbing lacunae and localization of a 100-kD lysosomal membrane protein at the osteoclast ruffled border",
      "volume": "101",
      "author": "Baron",
      "year": "1985",
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      "first-page": "1164",
      "DOI": "10.1083/jcb.102.4.1164",
      "article-title": "Isolated osteoclasts resorb the organic and inorganic components of bone",
      "volume": "102",
      "author": "Blair",
      "year": "1986",
      "journal-title": "J Cell Biol"
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    {
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      "first-page": "855",
      "DOI": "10.1126/science.2528207",
      "article-title": "Osteoclastic bone respoption by a polarized vacuolar proton pump",
      "volume": "245",
      "author": "Blair",
      "year": "1989",
      "journal-title": "Science"
    },
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      "key": "2024020713225312800_bib6",
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      "first-page": "1305",
      "DOI": "10.1083/jcb.111.3.1305",
      "article-title": "Evidence for the presence of a proton pump of the vacuolar H+-ATPase type in the ruffled borders of osteoclasts",
      "volume": "111",
      "author": "V\u00e4\u00e4n\u00e4nen",
      "year": "1990",
      "journal-title": "J Cell Biol"
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      "first-page": "18445",
      "DOI": "10.1016/S0021-9258(18)51486-1",
      "article-title": "H+-translocating ATPase in Golgi apparatus: Characterization as vacuolar H+-ATPase and its subunit structures",
      "volume": "264",
      "author": "Moriyama",
      "year": "1989",
      "journal-title": "J Biol Chem"
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      "article-title": "The evolution of H+-ATPases",
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      "author": "Nelson",
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      "first-page": "765",
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      "article-title": "Structure and function of vacuolar class of ATP-driven proton pumps",
      "volume": "69",
      "author": "Forgac",
      "year": "1989",
      "journal-title": "Physiol Rev"
    },
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      "doi-asserted-by": "crossref",
      "first-page": "3902",
      "DOI": "10.1021/bi00066a008",
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      "volume": "32",
      "author": "Dr\u00f6se",
      "year": "1993",
      "journal-title": "Biochemistry"
    },
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      "key": "2024020713225312800_bib11",
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      "first-page": "383",
      "DOI": "10.1111/j.1432-1033.1992.tb17061.x",
      "article-title": "Inhibition of the acidification of endosomes and lysosomes by the antibiotic concanamycin B in macrophage J774",
      "volume": "207",
      "author": "Woo",
      "year": "1992",
      "journal-title": "Eur J Biochem"
    },
    {
      "key": "2024020713225312800_bib12",
      "doi-asserted-by": "crossref",
      "first-page": "7972",
      "DOI": "10.1073/pnas.85.21.7972",
      "article-title": "Bafilomycins: A class of inhibitors of membrane ATPases from microorganisms, animal cells, and plant cells",
      "volume": "85",
      "author": "Bowman",
      "year": "1988",
      "journal-title": "Proc Natl Acad Sci USA"
    },
    {
      "key": "2024020713225312800_bib13",
      "doi-asserted-by": "crossref",
      "first-page": "21940",
      "DOI": "10.1016/S0021-9258(18)45829-2",
      "article-title": "The cytotoxic action of diphtheria toxin and its degradation in intact vero cells are inhibited by bafilomycin A1, a specific inhibitor of vacuolar-type H+-ATPase",
      "volume": "265",
      "author": "Umata",
      "year": "1990",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2024020713225312800_bib14",
      "doi-asserted-by": "crossref",
      "first-page": "309",
      "DOI": "10.1016/0006-291X(90)91709-2",
      "article-title": "Inhibition of osteoclast proton transport by bafilomycin A1 abolishes bone resorption",
      "volume": "168",
      "author": "Sundquist",
      "year": "1990",
      "journal-title": "Biochem Biophys Res Commun"
    },
    {
      "key": "2024020713225312800_bib15",
      "first-page": "265",
      "article-title": "Expression of vacuolar H+-ATPase in osteoclasts and its role in resorption",
      "volume": "278",
      "author": "Sasaki",
      "year": "1994",
      "journal-title": "Cell Tissue Res"
    },
    {
      "key": "2024020713225312800_bib16",
      "doi-asserted-by": "crossref",
      "first-page": "445",
      "DOI": "10.1002/jcp.1041570303",
      "article-title": "Inhibitors of vacuolar-type H+-ATPase suppresses proliferation of cultured cells",
      "volume": "157",
      "author": "Manabe",
      "year": "1993",
      "journal-title": "J Cell Physiol"
    },
    {
      "key": "2024020713225312800_bib17",
      "doi-asserted-by": "crossref",
      "first-page": "2600",
      "DOI": "10.1210/endo-123-5-2600",
      "article-title": "Induction of calcitonin receptors by 1\u03b1,25-dihydroxyvitamin D3 in osteoclast-like multinucleated cells formed from mouse bone marrow cells",
      "volume": "123",
      "author": "Takahashi",
      "year": "1988",
      "journal-title": "Endocrinology"
    },
    {
      "key": "2024020713225312800_bib18",
      "doi-asserted-by": "crossref",
      "first-page": "1297",
      "DOI": "10.1002/jbmr.5650071109",
      "article-title": "Preparation and characterization of a mouse osteoclast-like multinucleated cell population",
      "volume": "7",
      "author": "Akatsu",
      "year": "1992",
      "journal-title": "J Bone Miner Res"
    },
    {
      "key": "2024020713225312800_bib19",
      "doi-asserted-by": "crossref",
      "first-page": "79",
      "DOI": "10.1016/0014-5793(95)00153-Z",
      "article-title": "Wortmannin, a specific inhibitor of phosphatidylinositol-3 kinase, blocks osteoclastic bone resorption",
      "volume": "361",
      "author": "Nakamura",
      "year": "1995",
      "journal-title": "FEBS Lett"
    },
    {
      "key": "2024020713225312800_bib20",
      "doi-asserted-by": "crossref",
      "first-page": "4605",
      "DOI": "10.1074/jbc.271.9.4605",
      "article-title": "Interleukin-1\u03b1 activates an NF-\u03baB-like factor in osteoclast-like cells",
      "volume": "271",
      "author": "Jimi",
      "year": "1996",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2024020713225312800_bib21",
      "doi-asserted-by": "crossref",
      "first-page": "808",
      "DOI": "10.1210/endo.136.2.7835314",
      "article-title": "Macrophage colony-stimulating factor and interleukin-1\u03b1 maintain the survival of osteoclast-like cells",
      "volume": "136",
      "author": "Jimi",
      "year": "1995",
      "journal-title": "Endocrinology"
    },
    {
      "key": "2024020713225312800_bib22",
      "doi-asserted-by": "crossref",
      "first-page": "55",
      "DOI": "10.1016/0022-1759(83)90303-4",
      "article-title": "Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays",
      "volume": "65",
      "author": "Mossmann",
      "year": "1983",
      "journal-title": "J Immunol Meth"
    },
    {
      "key": "2024020713225312800_bib23",
      "doi-asserted-by": "crossref",
      "first-page": "1733",
      "DOI": "10.1084/jem.178.5.1733",
      "article-title": "Macrophage colony-stimulating factor stimulates survival and chemotactic behavior in isolated osteoclasts",
      "volume": "178",
      "author": "Fuller",
      "year": "1993",
      "journal-title": "J Exp Med"
    },
    {
      "key": "2024020713225312800_bib24",
      "doi-asserted-by": "crossref",
      "first-page": "493",
      "DOI": "10.1083/jcb.119.3.493",
      "article-title": "Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation",
      "volume": "119",
      "author": "Gavrieli",
      "year": "1992",
      "journal-title": "J Cell Biol"
    },
    {
      "key": "2024020713225312800_bib25",
      "doi-asserted-by": "crossref",
      "first-page": "397",
      "DOI": "10.1038/356397a0",
      "article-title": "Social controls on cell survival and cell death",
      "volume": "356",
      "author": "Raff",
      "year": "1992",
      "journal-title": "Nature"
    },
    {
      "key": "2024020713225312800_bib26",
      "doi-asserted-by": "crossref",
      "first-page": "126",
      "DOI": "10.1016/0167-5699(93)90214-6",
      "article-title": "Apoptosis",
      "volume": "14",
      "author": "Cohen",
      "year": "1993",
      "journal-title": "Immunol Today"
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      "article-title": "Osteoclasts undergo apoptosis at the interface between resorption and formation in bone remodelling units",
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      "author": "Wright",
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      "DOI": "10.1038/306378a0",
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      "volume": "136",
      "author": "Gowen",
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      "volume": "345",
      "author": "Yoshida",
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      "author": "Mattsson",
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      "article-title": "A vacuolar type H+-ATPase regulates cytoplasmic pH in murine macrophages",
      "volume": "265",
      "author": "Swallow",
      "year": "1990",
      "journal-title": "J Biol Chem"
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      "first-page": "782",
      "DOI": "10.1016/0006-291X(92)90814-2",
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      "volume": "186",
      "author": "Barry",
      "year": "1992",
      "journal-title": "Biochem Biophys Res Commun"
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      "volume": "92",
      "author": "Gottlieb",
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      "journal-title": "Proc Natl Acad Sci USA"
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      "volume": "270",
      "author": "Li",
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      "journal-title": "J Biol Chem"
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      "author": "Perez-Sala",
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      "author": "Hawkins",
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