Mechanism of osteoclast mediated bone resorption—rationale for the design of new therapeutics

VAANANEN, K

doi:10.1016/j.addr.2004.12.018

Cited by 176Bone Metabolism and DiseasesBone health and treatmentsBone health and osteoporosis research

Mechanism of osteoclast mediated bone resorption—rationale for the design of new therapeutics

VAANANEN, K·2005·Advanced Drug Delivery Reviews

DOI 10.1016/j.addr.2004.12.018

Open this paper in CoChat — free account

Abstract

Bone resorption is an important cellular function in the development and physiology of the skeleton. Pathophysiology of several skeletal diseases includes either increased (for instance osteoporosis, metastatic bone disease and Paget's disease of bone) or decreased (various syndromes of osteopetrosis) bone resorption rate. Thus there is a genuine need to regulate, especially inhibit, bone resorption rate in several diseases. Bone resorption can be inhibited by several strategies. One can prevent osteoclast formation, inhibit their action or induce premature cell death. All these strategies have been used in pharmacology to inhibit bone resorption and there are also physiological regulators for each of these three different phases of in osteoclast life. Many present resorption inhibitors inhibit osteoclast formation via osteoblastic cells since they are producing a number of factors that are essential for osteoclast differentiation. Best characterized of these factors are macrophage colony stimulating factor (M-CSF) and receptor activator of NFêB ligand (RANKL). For instance sex steroids, parathyroid hormone and some interleukins are known to exert their positive or negative effects on osteoclast differentiation via the RANK/RANKL/osteoprotegrin pathway. It is not yet clear enough how specific intervention to osteoclast formation is since also other cell lineages derived from hematopoetic precursors use similar signalling pathways. An effective inhibition of bone resorption can also be achieved by inhibiting osteoclast activity to resorb bone. Examples of this category of physiological and pharmacological inhibitors are calcitonin and aminobisphosphonates, respectively. Finally one can reduce bone resorption by shortening osteoclast lifespan with substances that induce apoptosis in osteoclasts. A good example of these substances is a first generation bisphosphonate, clodronate. Several new potential molecular targets have been revealed during recent years since many individual molecules in osteoclast differentiation, function and apoptosis have been identified and their physiological functions revealed. Thus we are expecting several new bone inhibitors to be developed in following years both for experimental studies and finally also for clinical use.

Integrity signals

Registry

Crossref · 10.1016/j.addr.2004.12.018

Cites

90 of 90 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Estrogen stimulates osteoblasts and osteocytes to produce osteoprotegerin (OPG), which inhibits osteoclastogenesis.
“Moreover, estrogen stimulates these bone cells to produce osteoprotegerin (OPG), a decoy receptor of RANK in osteoclast, thus inhibiting osteoclastogenesis [19, 155–159].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [158]

Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet, W. S., Lacey, D. L., Dunstan, C. R., Kelley, M., Chang, M.-S., Lüthy, R., Nguyen, H. Q., Wooden, S., Bennett, L., Boone, T., et al. (1997) · Cell · doi:10.1016/s0092-8674(00)80209-3 · Cited by 5,130 · see citing works
Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice
Soriano, P. M., Montgomery, C. A., Geske, R. S., & Bradley, A. (1991) · Cell · doi:10.1016/0092-8674(91)90499-o · Cited by 1,997 · see citing works
Principles of Bone Biology
(2019) · Elsevier eBooks · doi:10.1016/c2015-1-01622-2 · Cited by 1,690 · see citing works
Increased Osteoclast Development After Estrogen Loss: Mediation by Interleukin-6
Jilka, R. L., Hangoc, G., Girasole, G., Passeri, G., Williams, D. C., Abrams, J. S., Boyce, B. F., Broxmeyer, H. E., & Manolagas, S. C. (1992) · Science · doi:10.1126/science.1621100 · Cited by 1,440 · see citing works
Identity of Osteoclastogenesis Inhibitory Factor (OCIF) and Osteoprotegerin (OPG): A Mechanism by which OPG/OCIF Inhibits Osteoclastogenesis<i>in Vitro</i><sup>1</sup>
Yasuda, H., Shima, N., Nakagawa, N., Mochizuki, S.-I., Yano, K., Fujise, N., Sato, Y., Goto, M., Yamaguchi, K., Kuriyama, M., et al. (1998) · Endocrinology · doi:10.1210/endo.139.3.5837 · Cited by 1,201 · see citing works
TRANCE Is a Novel Ligand of the Tumor Necrosis Factor Receptor Family That Activates c-Jun N-terminal Kinase in T Cells
Wong, B. R., Rho, J., Arron, J. R., Robinson, E. A., Orlinick, J. R., Chao, M. V., Kalachikov, S. M., Cayani, E., Bartlett, F. S., Frankel, W. N., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.40.25190 · Cited by 1,042 · see citing works
Pycnodysostosis, a Lysosomal Disease Caused by Cathepsin K Deficiency
Gelb, B. D., Shi, G., Chapman, H. A., & Desnick, R. J. (1996) · Science · doi:10.1126/science.273.5279.1236 · Cited by 1,022 · see citing works
Loss of the ClC-7 Chloride Channel Leads to Osteopetrosis in Mice and Man
Kornak, U., Kasper, D., Bösl, M. R., Kaiser, E., Schweizer, M., Schulz, A., Friedrich, W., Delling, G., & Jentsch, T. J. (2001) · Cell · doi:10.1016/s0092-8674(01)00206-9 · Cited by 995 · see citing works
Clinical Implications of the Osteoprotegerin/RANKL/RANK System for Bone and Vascular Diseases
Hofbauer, L. C. (2004) · JAMA · doi:10.1001/jama.292.4.490 · Cited by 979 · see citing works
OSTEOBLASTIC CELLS ARE INVOLVED IN OSTEOCLAST FORMATION
Takahashi, N., Akatsu, T., Udagawa, N., Sasaki, T., Yamaguchi, A., Moseley, J. M., Martin, T. J., & Suda, T. (1988) · Endocrinology · doi:10.1210/endo-123-5-2600 · Cited by 934 · see citing works
Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice
Säftig, P., Hunziker, E. B., Wehmeyer, O., Jones, S. J., BOYDE, A., Rommerskirch, W., Moritz, J. D., Schu, P. V., & FIGURA, K. V. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.23.13453 · Cited by 909 · see citing works
Osteoclastic Bone Resorption by a Polarized Vacuolar Proton Pump
Blair, H. C., Teitelbaum, S. L., Ghiselli, R. W., & Gluck, S. L. (1989) · Science · doi:10.1126/science.2528207 · Cited by 862 · see citing works
Estrogen promotes apoptosis of murine osteoclasts mediated by TGF–β
Hughes, D. E., Dai, A., Tiffee, J. C., Li, H. H., Mundy, G. R., & Boyce, B. F. (1996) · Nature Medicine · doi:10.1038/nm1096-1132 · Cited by 813 · see citing works
Isolation of a novel cytokine from human fibroblasts that specifically inhibits osteoclastogenesis.
Tsuda, E., Goto, M., Mochizuki, S.-I., Yano, K., Kobayashi, F., Morinaga, T., & Higashio, K. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6603 · Cited by 787 · see citing works
Mice lacking beta3 integrins are osteosclerotic because of dysfunctional osteoclasts.
McHugh, K. P., Hodivala-Dilke, K., Zheng, M., Namba, N., Lam, J. D., Novack, D., Feng, X., Ross, F., Hynes, R. O., & Teitelbaum, S. L. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8905 · Cited by 786 · see citing works
Cathepsin K, but Not Cathepsins B, L, or S, Is Abundantly Expressed in Human Osteoclasts
Drake, F. H., Dodds, R. A., James, I. E., Connor, J. R., Debouck, C. M., Richardson, S. B., Lee-Rykaczewski, E., Coleman, L., Rieman, D. J., Barthlow, R., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.21.12511 · Cited by 721 · see citing works
STRUCTURE, FUNCTION AND REGULATION OF THE VACUOLAR (H+)-ATPase
Stevens, T. H., & Forgac, M. D. (1997) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.13.1.779 · Cited by 594 · see citing works
Proteolytic Activity of Human Osteoclast Cathepsin K
Bossard, M. J., Tomaszek, T. A., Thompson, S. K., Amegadzie, B. Y., Hanning, C. R., Jones, C. S., Kurdyla, J., McNulty, D. E., Drake, F. H., Gowen, M., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.21.12517 · Cited by 500 · see citing works
Removal of Osteoclast Bone Resorption Products by Transcytosis
Salo, J., Lehenkari, P. P., Mulari, M. T. K., Metsikkö, K., & Väänänen, H. K. (1997) · Science · doi:10.1126/science.276.5310.270 · Cited by 427 · see citing works
Tartrate-Resistant Acid Phosphatase 5b: A Novel Serum Marker of Bone Resorption
Halleen, J. M., Alatalo, S. L., Suominen, H., Cheng, S., Janckila, A. J., & Väänänen, H. K. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.7.1337 · Cited by 417 · see citing works
Resorption of bone by isolated rabbit osteoclasts
Chambers, T. J., Revell, P. A., Fuller, K., & Athanasou, N. A. (1984) · Journal of Cell Science · doi:10.1242/jcs.66.1.383 · Cited by 417 · see citing works
Alendronate Is a Specific, Nanomolar Inhibitor of Farnesyl Diphosphate Synthase
Bergstrom, J. D., Bostedor, R. G., Masarachia, P. J., Reszka, A. A., & Rodan, G. A. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1999.1502 · Cited by 402 · see citing works
Evidence for the presence of a proton pump of the vacuolar H(+)-ATPase type in the ruffled borders of osteoclasts.
Väänänen, H. K., Karhukorpi, E.-K., Sundquist, K. T., Wallmark, B., Roininen, I., Hentunen, T. A., Tuukkanen, J., & Lakkakorpi, P. T. (1990) · The Journal of Cell Biology · doi:10.1083/jcb.111.3.1305 · Cited by 391 · see citing works
Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone
Noble, B., Peet, N. M., Stevens, H. Y., Brabbs, A. C., Mosley, J. R., Reilly, G. C., REEVE, J., Skerry, T. M., & Lanyon, L. E. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00234.2002 · Cited by 381 · see citing works
Trafficking of Matrix Collagens Through Bone-Resorbing Osteoclasts
Nesbitt, S. A., & Horton, M. A. (1997) · Science · doi:10.1126/science.276.5310.266 · Cited by 378 · see citing works
Identification and Characterization of a Novel Related Adhesion Focal Tyrosine Kinase (RAFTK) from Megakaryocytes and Brain
Avraham, S., London, R., Fu, Y., Ota, S., Hiregowdara, D., Li, J., Jiang, S., Pasztor, L. M., White, R. A., Groopman, J. E., et al. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.46.27742 · Cited by 359 · see citing works
Molecular Cloning of Human cDNA for Cathepsin K: Novel Cysteine Proteinase Predominantly Expressed in Bone
Inaoka, T., Bilbe, G., Ishibashi, O., Tezuka, K., Kumegawa, M., & Kokubo, T. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.1013 · Cited by 352 · see citing works
Bone Resorption Restored in Osteopetrotic Mice by Transplants of Normal Bone Marrow and Spleen Cells
Walker, D. G. (1975) · Science · doi:10.1126/science.1105786 · Cited by 346 · see citing works
Osteoclast Differentiation Factor (ODF) Induces Osteoclast-like Cell Formation in Human Peripheral Blood Mononuclear Cell Cultures
Matsuzaki, K., Udagawa, N., Takahashi, N., Yamaguchi, K., Yasuda, H., Shima, N., Morinaga, T., Toyama, Y., Yabe, Y., Higashio, K., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8586 · Cited by 337 · see citing works
Resorption of dentine by isolated osteoclasts in vitro
BOYDE, A., Ali, N. N., & Jones, S. J. (1984) · BDJ · doi:10.1038/sj.bdj.4805313 · Cited by 295 · see citing works
c-Cbl is downstream of c-Src in a signalling pathway necessary for bone resorption
Tanaka, S., Amling, M., Neff, L., Peyman, A., Uhlmann, E., Levy, J. B., & Baron, R. (1996) · Nature · doi:10.1038/383528a0 · Cited by 288 · see citing works
Src Kinase Activity Is Essential for Osteoclast Function
Miyazaki, T., Sanjay, A., Neff, L., Tanaka, S., Horne, W. C., & Baron, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311032200 · Cited by 275 · see citing works
Intracellular Fragmentation of Bone Resorption Products by Reactive Oxygen Species Generated by Osteoclastic Tartrate-resistant Acid Phosphatase
Halleen, J. M., Räisänen, S. R., Salo, J. J., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.22907 · Cited by 263 · see citing works
Farnesol and Geranylgeraniol Prevent Activation of Caspases by Aminobisphosphonates: Biochemical Evidence for Two Distinct Pharmacological Classes of Bisphosphonate Drugs
Benford, H. L., Frith, J. C., Auriola, S. O. K., Mönkkönen, J., & Rogers, M. J. (1999) · Molecular Pharmacology · doi:10.1124/mol.56.1.131 · Cited by 255 · see citing works
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.
Duong, L. T., Lakkakorpi, P. T., Nakamura, I., Machwate, M., Nagy, R. M., & Rodan, G. A. (1998) · Journal of Clinical Investigation · doi:10.1172/jci3212 · Cited by 250 · see citing works
Characteristics of clodronate-induced apoptosis in osteoclasts and macrophages.
Selander, K. S., Mönkkönen, J., Karhukorpi, E.-K., et al. (1996) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09541-0 · Cited by 239 · see citing works
The osteoclast clear zone is a specialized cell-extracellular matrix adhesion structure
Väänänen, H. K., & Horton, M. A. (1995) · Journal of Cell Science · doi:10.1242/jcs.108.8.2729 · Cited by 217 · see citing works
Osteopetrosis Cured by Temporary Parabiosis
Walker, D. G. (1973) · Science · doi:10.1126/science.180.4088.875 · Cited by 194 · see citing works
Osteocytes inhibit osteoclastic bone resorption through transforming growth factor‐β: Enhancement by estrogen*
Heino, T. J., Hentunen, T. A., & Väänänen, H. K. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10109 · Cited by 191 · see citing works
Localization of cathepsin K in human osteoclasts by in situ hybridization and immunohistochemistry
Littlewood-Evans, A. J., Kokubo, T., Ishibashi, O., Inaoka, T., Wlodarski, B., Gallagher, J. A., & Bilbe, G. (1997) · Bone · doi:10.1016/s8756-3282(96)00351-1 · Cited by 190 · see citing works
Peptide Aldehyde Inhibitors of Cathepsin K Inhibit Bone Resorption Both In Vitro and In Vivo
Votta, B. J., Levy, M. A., Badger, A. M., Bradbeer, J. N., Dodds, R. A., James, I. E., Thompson, S. K., Bossard, M. J., Carr, T. J., Connor, J. R., et al. (1997) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1997.12.9.1396 · Cited by 185 · see citing works
Inhibition of osteoclast proton transport by bafilomycin A1 abolishes bone resorption
Sundquist, K. T., Lakkakorpi, P. T., Wallmark, B., & Väänänen, K. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)91709-2 · Cited by 173 · see citing works
Vitronectin receptor has a role in bone resorption but does not mediate tight sealing zone attachment of osteoclasts to the bone surface.
Lakkakorpi, P. T., Horton, M. A., Helfrich, M. H., Karhukorpi, E. K., & Väänänen, H. K. (1991) · The Journal of cell biology · doi:10.1083/jcb.115.4.1179 · Cited by 168 · see citing works
Endocytic pathway from the basal plasma membrane to the ruffled border membrane in bone-resorbing osteoclasts
Palokangas, H., Mulari, M. T. K., & Väänänen, H. K. (1997) · Journal of Cell Science · doi:10.1242/jcs.110.15.1767 · Cited by 168 · see citing works
Omeprazole, a specific inhibitor of H+−K+-ATPase, inhibits bone resorptionin vitro
Tuukkanen, J., & Väänänen, H. K. (1986) · Calcified Tissue International · doi:10.1007/bf02556841 · Cited by 167 · see citing works
Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway.
Virtanen, S. S., Väänänen, H. K., Härkönen, P. L., et al. (2002) · PubMed · Cited by 163 · see citing works
Identification of a Novel Phosphonocarboxylate Inhibitor of Rab Geranylgeranyl Transferase That Specifically Prevents Rab Prenylation in Osteoclasts and Macrophages
Coxon, F. P., Helfrich, M., Larijani, B., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106473200 · Cited by 161 · see citing works
High Extracellular Calcium Concentrations Directly Stimulate Osteoclast Apoptosis
Lorget, F., Kamel, S., Mentaverri, R., et al. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2229 · Cited by 161 · see citing works
A band of F-actin containing podosomes is involved in bone resorption by osteoclasts
Kanehisa, J., Yamanaka, T., Doi, S., et al. (1990) · Bone · doi:10.1016/8756-3282(90)90082-a · Cited by 157 · see citing works
Intracellular Machinery for Matrix Degradation in Bone-Resorbing Osteoclasts
Vääräniemi, J. P., Halleen, J. M., Kaarlonen, K., et al. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.040603 · Cited by 152 · see citing works
Fatigue Microdamage as an Essential Element of Bone Mechanics and Biology
Martin, R. B. (2003) · Calcified Tissue International · doi:10.1007/s00223-002-1059-9 · Cited by 148 · see citing works
Cells of Bone
Takahashi, N., Udagawa, N., Takami, M., & Suda, T. (2002) · Elsevier eBooks · doi:10.1016/b978-012098652-1/50109-8 · Cited by 147 · see citing works
Downregulation of Small GTPase Rab7 Impairs Osteoclast Polarization and Bone Resorption
Zhao, H., Laitala‐Leinonen, T., Parikka, V., & Väänänen, H. K. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010999200 · Cited by 141 · see citing works
Die normale Resorption des Knochengewebes und ihre Bedeutung für die Entstehungder typischen Knochenformen
Kölliker, A. (1873) · Cited by 140 · see citing works
Carbonic Anhydrase and Bone Remodeling: Sulfonamide Inhibition of Bone Resorption in Organ Culture
Minkin, C., & Jennings, J. M. (1972) · Science · doi:10.1126/science.176.4038.1031 · Cited by 138 · see citing works
A selective inhibitor of the osteoclastic V-H+-ATPase prevents bone loss in both thyroparathyroidectomized and ovariectomized rats
Visentin, L., Dodds, R. A., Valente, M., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci6145 · Cited by 131 · see citing works
A nonsense mutation in the cathepsin K gene observed in a family with pycnodysostosis.Preprint
Johnson, M. R., Polymeropoulos, M. H., Vos, H. L., Luna, R. I. O. D., & Francomano, C. A. (1996) · Genome Research · doi:10.1101/gr.6.11.1050 · Cited by 130 · see citing works
Spleen Cells Transmit Osteopetrosis in Mice
Walker, D. G. (1975) · Science · doi:10.1126/science.1198094 · Cited by 129 · see citing works
Osteoprotegerin and osteoprotegerin ligand effects on osteoclast formation from human peripheral blood mononuclear cell precursors
Shalhoub, V., Faust, J., Boyle, W. J., Dunstan, C. R., Kelley, M., Kaufman, S., Scully, S. A., Van, G. Y., & Lacey, D. L. (1999) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(19990201)72:2 · Cited by 123 · see citing works
Estrogen Reduces the Depth of Resorption Pits by Disturbing the Organic Bone Matrix Degradation Activity of Mature Osteoclasts
Parikka, V., Lehenkari, P. P., Sassi, M.-L., Halleen, J. M., Risteli, J., Härkönen, P. L., & Väänänen, H. K. (2001) · Endocrinology · doi:10.1210/endo.142.12.8533 · Cited by 118 · see citing works
The effects of bisphosphonates on the resorption cycle of isolated osteoclasts
Selander, K. S., Lehenkari, P. P., & V��n�nen, H. K. (1994) · Calcified Tissue International · doi:10.1007/bf00299317 · Cited by 117 · see citing works
Calcitonin-induced changes in the cytoskeleton are mediated by a signal pathway associated with protein kinase A in osteoclasts
Suzuki, H., Nakamura, I., Takahashi, N., Ikuhara, T., Matsuzaki, K., Isogai, Y., Hori, M., & Suda, T. (1996) · Endocrinology · doi:10.1210/endo.137.11.8895334 · Cited by 114 · see citing works
Stable Association of PYK2 and p130Cas in Osteoclasts and Their Co-localization in the Sealing Zone
Lakkakorpi, P. T., Nakamura, I., Nagy, R. M., Parsons, J. T., Rodan, G. A., & Duong, L. T. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.8.4900 · Cited by 112 · see citing works
Vinculin, talin, and integrins are localized at specific adhesion sites of malignant B lymphocytes
Marchisio, P., Bergui, L., Corbascio, G., Cremona, O., D'Urso, N., Schena, M., Tesio, L., & Caligaris‐Cappio, F. (1988) · Blood · doi:10.1182/blood.v72.2.830.830 · Cited by 109 · see citing works
Intracellular membrane trafficking in bone resorbing osteoclasts
Mulari, M., Vääräniemi, J., & Väänänen, H. K. (2003) · Microscopy Research and Technique · doi:10.1002/jemt.10371 · Cited by 104 · see citing works
Alendronate Disturbs Vesicular Trafficking in Osteoclasts
Alakangas, A., Selander, K. S., Mulari, M. T. K., et al. (2002) · Calcified Tissue International · doi:10.1007/s002230010047 · Cited by 103 · see citing works
Effects of Bafilomycin A1: An inhibitor of vacuolar H (+)‐ATPases on endocytosis and apoptosis in RAW cells and RAW cell‐derived osteoclasts
Xu, J., Feng, H. T., Wang, C., Yip, K. H. M., Pavlos, N. J., Papadimitriou, J. M., Wood, D., & Zheng, M. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10477 · Cited by 99 · see citing works
Bone-resorbing osteoclasts reveal a dynamic division of basal plasma membrane into two different domains
Salo, J., Metsikkö, K., Palokangas, H., Lehenkari, P. P., & Väänänen, H. K. (1996) · Journal of Cell Science · doi:10.1242/jcs.109.2.301 · Cited by 98 · see citing works
Convergence of αvβ3Integrin–And Macrophage Colony Stimulating Factor–Mediated Signals on Phospholipase Cγ in Prefusion Osteoclasts
Nakamura, I., Lipfert, L., Rodan, G. A., & Duong, L. T. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.2.361 · Cited by 96 · see citing works
The Role of Prenylated Small GTP-Binding Proteins in the Regulation of Osteoclast Function
Coxon, F. P., & Rogers, M. J. (2003) · Calcified Tissue International · doi:10.1007/s00223-002-2017-2 · Cited by 94 · see citing works
Tartrate-resistant acid phosphatase from human bone: Purification and development of an immunoassay
Halleen, J. M., Hentunen, T. A., Hellman, J., et al. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650111011 · Cited by 76 · see citing works
Potential Function for the ROS-Generating Activity of TRACP
Halleen, J. M., Räisänen, S. R., Alatalo, S. L., et al. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.10.1908 · Cited by 70 · see citing works
Inhibition of Osteoclast Function by Adenovirus Expressing Antisense Protein-tyrosine Kinase 2
Duong, L. T., Nakamura, I., Lakkakorpi, P. T., Lipfert, L., Bett, A. J., & Rodan, G. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008368200 · Cited by 63 · see citing works
Local Regulators of Bone: IL-1, TNF, Lymphotoxin, Interferon-γ, IL-8, IL-10, IL-4, the LIF/IL-6 Family, and Additional Cytokines
Horowitz, M., & Lorenzo, J. (2002) · Elsevier eBooks · doi:10.1016/b978-012098652-1.50155-4 · Cited by 60 · see citing works
Calcitonin promotes osteoclast survival in vitro
Selander, K. S., Härkönen, P. L., Valve, E. M., Mönkkönen, J., Hannuniemi, R., & Väänänen, H. K. (1996) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(96)03870-1 · Cited by 59 · see citing works
Intracellular membrane trafficking pathways in bone-resorbing osteoclasts revealed by cloning and subcellular localization studies of small GTP-binding rab proteins
Zhao, H., Ettala, O. O., & Väänänen, H. K. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00326-1 · Cited by 57 · see citing works
Transitional structures in lamellar bone
Ziv, V., Sabanay, I., Arad, T., Traub, W., & Weiner, S. (1996) · Microscopy Research and Technique · doi:10.1002/(sici)1097-0029(19960201)33:2 · Cited by 55 · see citing works
Purification of a stilbene sensitive chloride channel and reconstitution of chloride conductivity into phospholipid vesicles
Blair, H. C., & Schlesinger, P. H. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)90771-e · Cited by 52 · see citing works
Bafilomycin A1 inhibits bone resorption and tooth eruption in vivo
Sundquist, K. T., & Marks, S. C. (1994) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650091010 · Cited by 51 · see citing works
Calcitonin, prostaglandin E2, and dibutyryl cyclic adenosine 3',5'-monophosphate disperse the specific microfilament structure in resorbing osteoclasts.
Lakkakorpi, P. T., & Väänänen, H. K. (1990) · Journal of Histochemistry & Cytochemistry · doi:10.1177/38.10.2169493 · Cited by 51 · see citing works
A novel inhibitor of vacuolar ATPase, FR167356, which can discriminate between osteoclast vacuolar ATPase and lysosomal vacuolar ATPase
Niikura, K., Takano, M., & Sawada, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705812 · Cited by 46 · see citing works
Vesicle Transport: A Close Collaboration of Rabs and Effectors
Spang, A. (2004) · Current Biology · doi:10.1016/j.cub.2003.12.021 · Cited by 44 · see citing works
Selective toxic effects of tamoxifen on osteoclasts: comparison with the effects of oestrogen
Arnett, T. R., Lindsay, R., Kilb, J. M., et al. (1996) · Journal of Endocrinology · doi:10.1677/joe.0.1490503 · Cited by 36 · see citing works
The architecture of microtubular network and Golgi orientation in osteoclasts—major differences between avian and mammalian species
Mulari, M. T. K., Patrikainen, L., Kaisto, T., Metsikkö, K., Salo, J. J., & Väänänen, H. K. (2003) · Experimental Cell Research · doi:10.1016/s0014-4827(03)00033-8 · Cited by 30 · see citing works
The Effects of Tamoxifen and Toremifene on Bone Cells Involve Changes in Plasma Membrane Ion Conductance
Lehenkari, P. P., Parikka, V., Rautiala, T., Weckström, M., Dahllund, J., Härkönen, P. L., & Väänänen, H. K. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.3.473 · Cited by 29 · see citing works
- activity is essential for the induction, but not the maintenance of osteoclastic bone resorption and cytoplasmic spreading
Hall, T. J., Schaeublin, M., & Chambers, T. J. (1992) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(92)91344-p · Cited by 28 · see citing works
EFFECT OF OESTRADIOL ON CYTOKINE PRODUCTION IN IMMORTALIZED HUMAN MARROW STROMAL CELL LINES
Ramalho, A. C., Jullienne, A., Couttet, P., Graulet, A. M., Morieux, C., de Vernejoul, M. C., & Cohen-Solal, M. E. (2001) · Cytokine · doi:10.1006/cyto.2001.0956 · Cited by 19 · see citing works
Tissue-selective inhibition of vacuolar acid pumps.
Keeling, D. J., Herslöf, M., Mattsson, J. P., et al. (1998) · PubMed · Cited by 14 · see citing works
Integrin and Calcitonin Receptor Signaling in the Regulation of the Cytoskeleton and Function of Osteoclasts
Duong, L. T., Sanjay, A., Horne, W. C., Baron, R., & Rodan, G. A. (2002) · Elsevier eBooks · doi:10.1016/b978-012098652-1.50111-6 · Cited by 5 · see citing works
Untitled work
Good (1996) · doi:10.1002/(sici)1097-4652(199609)168:3

Flagged first, then by citations

Sorted by citations

Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells
Florencio-Silva, R., Sasso, G. R. D. S., Sasso-Cerri, E., Simões, M. J., & Cerri, P. S. (2015) · BioMed Research International · doi:10.1155/2015/421746 · Cited by 2,044 · see citing works
Salmon calcitonin: a review of current and future therapeutic indications
Chesnut, C. H., Azria, M., Silverman, S., Engelhardt, M., Olson, M., & Mindeholm, L. (2008) · Osteoporosis International · doi:10.1007/s00198-007-0490-1 · Cited by 216 · see citing works
Immunohistochemical detection of estrogen receptor β in alveolar bone cells of estradiol‐treated female rats: possible direct action of estrogen on osteoclast life span
Cruzoé‐Souza, M., Sasso‐Cerri, E., & Cerri, P. S. (2009) · Journal of Anatomy · doi:10.1111/j.1469-7580.2009.01158.x · Cited by 38 · see citing works

An inhibitory role for caspase‐3 at the late stage of RANKL‐induced osteoclast differentiation in RAW264 cells and mouse bone marrow macrophages
Katao, Y., Shishido, M., Inami, K., Matsumoto, N., & Sawai, H. (2014) · Cell Biology International · doi:10.1002/cbin.10263 · Cited by 4 · see citing works
64Cu-RGD and microPET/CT as an imaging biomarker for osteoclast number in mouse models of negative and positive osteoclast regulation
Zheleznyak, A., Wadas, T. J., Sherman, C., et al. (2009) · Journal of Nuclear Medicine
The effects of tumor necrosis factor-α on osteoclast formation depend on the haematopoietic precursors
Portenier, J., Dolder, S., Wetterwald, A., et al. (2006) · Bone · doi:10.1016/j.bone.2006.01.113
Inhibitory Effect of Agrocybe Chaxingu (Chaxines) on RANKL-Induced Osteoclast Differentiation in RAW246.7 Cells: Possible Prevention of Osteoporosis
Konno, S., Elyaguov, J., Dixon, A., et al. (2022) · American Journal of Medical and Clinical Sciences · doi:10.33425/2832-4226/22005 · Cited by 1 · see citing works
RANKL as the master regulator of osteoclast differentiation
Takayanagi, H. (2021) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-020-01191-1 · Cited by 175 · see citing works

Authors: VAANANEN, K.
Venue: Advanced Drug Delivery Reviews
Publisher: Elsevier BV
Published: 2005-05-25
Volume: 57
Issue: 7
Pages: 959-971
ISSN: 0169-409X (ISSN-L)
DOI: 10.1016/j.addr.2004.12.018
OpenAlex: W2052354535
Cited by: 176
References: 90
Citations by year: 2026: 5 · 2025: 1 · 2024: 6 · 2023: 7 · 2022: 5 · 2021: 18 · 2020: 7 · 2019: 8 · 2018: 10 · 2017: 3 · 2016: 6 · 2015: 10 · 2014: 6 · 2013: 9 · 2012: 8
FWCI: 4.52
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Advanced Drug Delivery Reviews (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Oncology › Bone health and treatments
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords: osteoclasts, bone resorption, osteoclastogenesis, RANKL, macrophage colony-stimulating factor, osteoblasts, bisphosphonates, calcitonin, clodronate, osteoclast apoptosis, osteoporosis, Paget's disease of bone, osteopetrosis, antiresorptive agents, therapeutic target
MeSH terms: Bone Matrix, Bone Resorption, Calcitonin, Carrier Proteins, Cell Differentiation, Diphosphonates, Humans, Membrane Glycoproteins, Osteoclasts, Drug Design, Macrophage Colony-Stimulating Factor, Apoptosis, Selective Estrogen Receptor Modulators, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Mechanism of osteoclast mediated bone resorption—rationale for the design of new therapeutics

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks