Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology

Hofbauer, Lorenz C.; Heufelder, Armin E.

doi:10.1007/s001090100226

Cited by 586Bone Metabolism and DiseasesBone health and osteoporosis researchRheumatoid Arthritis Research and Therapies

Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology

Hofbauer, Lorenz C., Heufelder, Armin E.·2001·Journal of Molecular Medicine

DOI 10.1007/s001090100226

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Abstract

Receptor activator of nuclear factor (NF-kappaB) ligand (RANKL), its cellular receptor, receptor activator of NF-kappaB (RANK), and the decoy receptor osteoprotegerin (OPG) constitute a novel cytokine system. RANKL produced by osteoblastic lineage cells and activated T lymphocytes is the essential factor for osteoclast formation, fusion, activation, and survival, thus resulting in bone resorption and bone loss. RANKL activates its specific receptor, RANK located on osteoclasts and dendritic cells, and its signaling cascade involves stimulation of the c-jun, NF-kappaB, and serine/threonine kinase PKB/Akt pathways. The effects of RANKL are counteracted by OPG which acts as a soluble neutralizing receptor. RANKL and OPG are regulated by various hormones (glucocorticoids, vitamin D, estrogen), cytokines (tumor necrosis factor alpha, interleukins 1, 4, 6, 11, and 17), and various mesenchymal transcription factors (such as cbfa-1, peroxisome proliferator-activated receptor gamma, and Indian hedgehog). Transgenic and knock-out mice with excessive or defective production of RANKL, RANK, and OPG display the extremes of skeletal phenotypes, osteoporosis and osteopetrosis. Abnormalities of the RANKL/OPG system have been implicated in the pathogenesis of postmenopausal osteoporosis, rheumatoid arthritis, Paget's disease, periodontal disease, benign and malignant bone tumors, bone metastases, and hypercalcemia of malignancy, while administration of OPG has been demonstrated to prevent or mitigate these disorders in animal models. RANKL and OPG are also important regulators of vascular biology and calcification and of the development of a lactating mammary gland during pregnancy, indicating a crucial role for this system in extraskeletal calcium handling. The discovery and characterization of RANKL, RANK, and OPG and subsequent studies have changed the concepts of bone and calcium metabolism, have led to a detailed understanding of the pathogenesis of metabolic bone diseases, and may form the basis of innovative therapeutic strategies.

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“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 [155]

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Lubberts, E., Joosten, L. A. B., Chabaud, M., van den Bersselaar, L., Oppers‐Walgreen, B., Roo, C. J. J. C., Richards, C. D., Miossec, P., & van den Berg, W. B. (2000) · Journal of Clinical Investigation · doi:10.1172/jci7739 · Cited by 309 · see citing works
OPG/FDCR-1, a TNF receptor family member, is expressed in lymphoid cells and is up-regulated by ligating CD40.
Yun, T. J., Chaudhary, P. M., Shu, G. L., Frazer, J. K., Ewings, M. K., Schwartz, S. M., Pascual, V., Hood, L. E., & Clark3, E. A. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.11.6113 · Cited by 307 · see citing works
Transforming Growth Factor-β Stimulates the Production of Osteoprotegerin/Osteoclastogenesis Inhibitory Factor by Bone Marrow Stromal Cells
Takai, H., Kanematsu, M., Yano, K., Tsuda, E., Higashio, K., Ikeda, K., Watanabe, K., & Yamada, Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.42.27091 · Cited by 299 · see citing works
The Expression of Osteoprotegerin and RANK Ligand and the Support of Osteoclast Formation by Stromal-Osteoblast Lineage Cells Is Developmentally Regulated**This work was supported by Grant AG-04875 from the National Institute on Aging.
Gori, F., Hofbauer, L. C., Dunstan, C. R., Spelsberg, T. C., Khosla, S., & Riggs, B. L. (2000) · Endocrinology · doi:10.1210/endo.141.12.7840 · Cited by 297 · see citing works
Self-citation
Characterization of a novel TNF-like ligand and recently described TNF ligand and TNF receptor superfamily genes and their constitutive and inducible expression in hematopoietic and non-hematopoietic cells
Tan, K. B., Harrop, J., Reddy, M. P., Young, P. R., Terrett, J. A., Emery, J. G., Moore, G. P., & Truneh, A. (1997) · Gene · doi:10.1016/s0378-1119(97)00509-x · Cited by 277 · see citing works
Gene Expression of Osteoprotegerin Ligand, Osteoprotegerin, and Receptor Activator of NF-κB in Giant Cell Tumor of Bone
Huang, L., Xu, J., Wood, D., et al. (2000) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)64942-5 · Cited by 260 · see citing works
TRANCE, a tumor necrosis factor family member critical for CD40 ligand-independent T helper cell activation.
Bachmann, M. F., Wong, B. R., Josien, R., Steinman, R. M., Oxenius, A., & Choi, Y. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.7.1025 · Cited by 260 · see citing works
Transcriptional autoregulation of the bone related CBFA1/RUNX2 gene
Drissi, H., Luc, Q., Shakoori, R., Lopes, S. M. C. D. S., Choi, J., Terry, A., Hu, M., Jones, S. N., Neil, J. C., Lian, J. B., et al. (2000) · Journal of Cellular Physiology · doi:10.1002/1097-4652(200009)184:3 · Cited by 251 · see citing works
Osteoprotegerin Serum Levels in Men: Correlation with Age, Estrogen, and Testosterone Status
Szulc, P., Hofbauer, L. C., Heufelder, A. E., Roth, S., & Delmas, P. D. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.7.7657 · Cited by 250 · see citing works
Self-citation
TRANCE is a TNF family member that regulates dendritic cell and osteoclast function
Wong, B. R., Josien, R., & Choi, Y. (1999) · Journal of Leukocyte Biology · doi:10.1002/jlb.65.6.715 · Cited by 230 · see citing works
Expression of Osteoclast Differentiation Signals by Stromal Elements of Giant Cell Tumors
Atkins, G. J., Haynes, D. R., Graves, S. E., Evdokiou, A., Hay, S. J., Bouralexis, S., & Findlay, D. M. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.4.640 · Cited by 197 · see citing works
Transforming Growth Factor-β1 Increases mRNA Levels of Osteoclastogenesis Inhibitory Factor in Osteoblastic/Stromal Cells and Inhibits the Survival of Murine Osteoclast-like Cells
Murakami, T., Yamamoto, M., Yamamoto, M., Ono, K., Nishikawa, M., Nagata, N., Motoyoshi, K., & Akatsu, T. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9723 · Cited by 195 · see citing works
A chimeric form of osteoprotegerin inhibits hypercalcemia and bone resorption induced by IL-1β, TNF-α, PTH, PTHrP, and 1,25(OH)2D3.
Morony, S., Capparelli, C., Lee, R., Shimamoto, G., Boone, T., Lacey, D. L., & Dunstan, C. R. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.9.1478 · Cited by 187 · see citing works
Osteoprotegerin mRNA is expressed in primary human osteoblast-like cells: down-regulation by glucocorticoids.
Vidal, N., Brandstrom, H., Jonsson, K., & Ohlsson, C. (1998) · Journal of Endocrinology · doi:10.1677/joe.0.1590191 · Cited by 185 · see citing works
The Osteoblast-specific Transcription Factor Cbfa1 Contributes to the Expression of Osteoprotegerin, a Potent Inhibitor of Osteoclast Differentiation and Function
Thirunavukkarasu, K., Halladay, D., Miles, R. R., Yang, X., Galvin, R. J. S., Chandrasekhar, S., Martin, T. J., & Onyia, J. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m000322200 · Cited by 181 · see citing works
TR1, a new member of the tumor necrosis factor receptor superfamily, induces fibroblast proliferation and inhibits osteoclastogenesis and bone resorption
Kwon, B. S., Wang, S., Udagawa, N., Haridas, V., Lee, Z. H., Kim, K. K., Oh, K., Greene, J., Li, Y., Su, J. Y., et al. (1998) · The FASEB Journal · doi:10.1096/fasebj.12.10.845 · Cited by 179 · see citing works
Prostaglandin E2 Cooperates with TRANCE in Osteoclast Induction from Hemopoietic Precursors: Synergistic Activation of Differentiation, Cell Spreading, and Fusion
Wani, M. R., Fuller, K., Kim, N. S., Choi, Y., & Chambers, T. J. (1999) · Endocrinology · doi:10.1210/endo.140.4.6647 · Cited by 172 · see citing works
Enhanced RANK ligand expression and responsivity of bone marrow cells in Paget’s disease of bone.
Menaa, C., Reddy, S. V., Kurihara, N., Maeda, H., Anderson, D., Cundy, T., Cornish, J., Singer, F. R., Bruder, J. M., & Roodman, G. D. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9133 · Cited by 154 · see citing works
Promoter structure of mouse RANKL/TRANCE/OPGL/ODF gene
Kitazawa, R., Kitazawa, S., & Maeda, S. (1999) · Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression · doi:10.1016/s0167-4781(99)00032-9 · Cited by 153 · see citing works
New insights into role of microenvironment in multiple myeloma
Tricot, G. J. K. (2000) · The Lancet · doi:10.1016/s0140-6736(00)00019-2 · Cited by 149 · see citing works
Osteoprotegerin prevents and reverses hypercalcemia in a murine model of humoral hypercalcemia of malignancy.
Capparelli, C., Kostenuik, P. J., Morony, S., Starnes, C. O., Weimann, B., Van, G. Y., Scully, S. A., Qi, M., Lacey, D. L., & Dunstan, C. R. (2000) · PubMed · Cited by 147 · see citing works
Fibroblastic Stromal Cells Express Receptor Activator of NF-κB Ligand and Support Osteoclast Differentiation
Quinn, J. M. W., Horwood, N. J., Elliott, J., Gillespie, M. T., & Martin, T. J. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.8.1459 · Cited by 141 · see citing works
Mechanical strain inhibits expression of osteoclast differentiation factor by murine stromal cells
Rubin, J. E., Murphy, T., Nanes, M. S., & Fan, X. (2000) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.2000.278.6.c1126 · Cited by 138 · see citing works
TGF-β Enhances Osteoclast Differentiation in Hematopoietic Cell Cultures Stimulated with RANKL and M-CSF
Galvin, R. J. S., Gatlin, C. L., Horn, J. W., & Fuson, T. R. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1632 · Cited by 132 · see citing works
Potential Role of Cbfa1, an Essential Transcriptional Factor for Osteoblast Differentiation, in Osteoclastogenesis: Regulation of mRNA Expression ofOsteoclast Differentiation Factor(ODF)
Gao, Y., Shinki, T., Yuasa, T., Kataoka-Enomoto, H., Komori, T., Suda, T., & Yamaguchi, A. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9643 · Cited by 131 · see citing works
Regulation of Osteoprotegerin mRNA Levels by Prostaglandin E2in Human Bone Marrow Stroma Cells
Brändström, H., Jonsson, K. B., Ohlsson, C., Vidal, O., Ljunghall, S., & Ljunggren, Ö. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8783 · Cited by 131 · see citing works
In Vivo Demonstration that Human Parathyroid Hormone 1–38 Inhibits the Expression of Osteoprotegerin in Bone with the Kinetics of an Immediate Early Gene
Onyia, J. E., Miles, R. R., Yang, X., Halladay, D. L., Hale, J. E., GLASEBROOK, A. L., McClure, D. B., Seno, G., Churgay, L. M., Chandrasekhar, S., et al. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.5.863 · Cited by 124 · see citing works
Osteoclastogenesis inhibitory factor suppresses osteoclast survival by interfering in the interaction of stromal cells with osteoclast.
Akatsu, T., Murakami, T., Nishikawa, M., Ono, K., Shinomiya, N., Tsuda, E., Mochizuki, S.-I., Yamaguchi, K., Kinosaki, M., Higashio, K., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9294 · Cited by 123 · see citing works
Activation of Peroxisome Proliferator-activated Receptor-γ Pathway Inhibits Osteoclast Differentiation
Mbalaviele, G., Abu‐Amer, Y., Meng, A., Jaiswal, R. K., Beck, S., Pittenger, M. F., Thiede, M. A., & Marshak, D. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.19.14388 · Cited by 113 · see citing works
Activin A Is an Essential Cofactor for Osteoclast Induction
Fuller, K., Bayley, K. E., & Chambers, T. J. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2075 · Cited by 113 · see citing works
Reciprocal gene expression of osteoclastogenesis inhibitory factor and osteoclast differentiation factor regulates osteoclast formation.
Nagai, M., & Sato, N. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0524 · Cited by 111 · see citing works
Osteoclast differentiation from circulating mononuclear precursors in Paget’s disease is hypersensitive to 1,25-dihydroxyvitamin D3 and RANKL
Neale, S. D., Smith, R., Wass, J. A. H., & Athanasou, N. A. (2000) · Bone · doi:10.1016/s8756-3282(00)00345-8 · Cited by 110 · see citing works
Osteoclastogenesis inhibitory factor (OCIF) directly inhibits bone-resorbing activity of isolated mature osteoclasts.
Hakeda, Y., Kobayashi, Y., Yamaguchi, K., Yasuda, H., Tsuda, E., Higashio, K., Miyata, T., & Kumegawa, M. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9523 · Cited by 107 · see citing works
Osteoprotegerin mRNA Is Increased by Interleukin-1α in the Human Osteosarcoma Cell Line MG-63 and in Human Osteoblast-Like Cells
Vidal, O., Sjögren, K., Eriksson, B. I., Ljunggren, Ö., & Ohlsson, C. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9035 · Cited by 105 · see citing works
Expression of Osteoprotegerin (Osteoclastogenesis Inhibitory Factor) in Cultures of Human Dental Mesenchymal Cells and Epithelial Cells
Sakata, M., Shiba, H., Komatsuzawa, H., Fujita, T., Ohta, K., Sugai, M., Suginaka, H., & Kurihara, H. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.9.1486 · Cited by 103 · see citing works
Tumor Necrosis Factor-α and -β Upregulate the Levels of Osteoprotegerin mRNA in Human Osteosarcoma MG-63 Cells
Brändström, H., Jonsson, K. B., Vidal, O., Ljunghall, S., Ohlsson, C., & Ljunggren, Ö. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8993 · Cited by 102 · see citing works
1,25-Dihydroxyvitamin D3 Hypersensitivity of Osteoclast Precursors from Patients with Paget's Disease
Menaa, C., Bársony, J., Reddy, S. V., Cornish, J., Cundy, T., & Roodman, G. D. (2000) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2000.15.2.228 · Cited by 98 · see citing works
Age-Related Decline in Osteoprotegerin Expression by Human Bone Marrow Cells Cultured in Three-Dimensional Collagen Sponges
Makhluf, H. A., Mueller, S. M., Mizuno, S., & Glowacki, J. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2182 · Cited by 96 · see citing works
Interactions between cancer and bone marrow cells induce osteoclast differentiation factor expression and osteoclast-like cell formation in vitro.
Chikatsu, N., Takeuchi, Y., Tamura, Y., Fukumoto, S., Yano, K., Tsuda, E., Ogata, E., & Fujita, T. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.2008 · Cited by 95 · see citing works
Cancer Cells Responsible for Humoral Hypercalcemia Express mRNA Encoding a Secreted Form of ODF/TRANCE That Induces Osteoclast Formation
Nagai, M., Kyakumoto, S., & Sato, N. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2314 · Cited by 93 · see citing works
Dental Cells Express Factors That Regulate Bone Resorption
Rani, C. S. S., & MacDougall, M. J. (2000) · Molecular Cell Biology Research Communications · doi:10.1006/mcbr.2000.0205 · Cited by 92 · see citing works
Osteoclastogenesis inhibitory factor exhibits hypocalcemic effects in normal mice and in hypercalcemic nude mice carrying tumors associated with humoral hypercalcemia of malignancy.
Akatsu, T., Murakami, T., Ono, K., Nishikawa, M., Tsuda, E., Mochizuki, S.-I., Fujise, N., Higashio, K., Motoyoshi, K., Yamamoto, M., et al. (1998) · Bone · doi:10.1016/s8756-3282(98)00141-0 · Cited by 87 · see citing works
The Inhibitory Effects of Vasoactive Intestinal Peptide and Pituitary Adenylate Cyclase-Activating Polypeptide on Osteoclast Formation Are Associated with Upregulation of Osteoprotegerin and Downregulation of RANKL and RANK
Mukohyama, H., Ransjö, M., Taniguchi, H., Ohyama, T., & Lerner, U. H. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.2599 · Cited by 85 · see citing works
Characterization of monomeric and homodimeric forms of osteoclastogenesis inhibitory factor.
Tomoyasu, A., Goto, M., Fujise, N., Mochizuki, S.-I., Yasuda, H., Morinaga, T., Tsuda, E., & Higashio, K. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8443 · Cited by 83 · see citing works
RANKing the importance of measles virus in Paget’s disease
Ross, F. P. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9557 · Cited by 79 · see citing works
Expression of functional RANK on mature rat and human osteoclasts
Myers, D. E., Collier, F. M., Minkin, C., Wang, H., Holloway, W. R., Malakellis, M., & Nicholson, G. C. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01650-6 · Cited by 76 · see citing works
The effect of environmental cues on the differentiation of myofibroblasts in peritoneal granulation tissue
(2000) · doi:10.1002/1096-9896(2000)9999:9999 · Cited by 70 · see citing works
Osteoprotegerin mitigates tail suspension-induced osteopenia.
Bateman, T. A., Dunstan, C. R., Ferguson, V. L., Lacey, D. L., Ayers, R. A., & Simske, S. J. (2000) · Bone · doi:10.1016/s8756-3282(00)00256-8 · Cited by 66 · see citing works
Hypocalcemic Effect of Osteoclastogenesis Inhibitory Factor/Osteoprotegerin in the Thyroparathyroidectomized Rat
Yamamoto, M., Murakami, T., Nishikawa, M., Tsuda, E., Mochizuki, S.-I., Higashio, K., Akatsu, T., Motoyoshi, K., & Nagata, N. (1998) · Endocrinology · doi:10.1210/endo.139.9.6290 · Cited by 65 · see citing works
Basic fibroblast growth factor induces osteoclast formation by reciprocally regulating the production of osteoclast differentiation factor and osteoclastogenesis inhibitory factor in mouse osteoblastic cells.
Nakagawa, N., Yasuda, H., Yano, K., Mochizuki, S.-I., Kobayashi, N., Fujimoto, H., Shima, N., Morinaga, T., Chikazu, D., Kawaguchi, H., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1601 · Cited by 64 · see citing works
Establishment and Characterization of an Immortal Macrophage-like Cell Line Inducible to Differentiate to Osteoclasts
Miyamoto, A., Kunisada, T., Hemmi, H., Yamane, T., Yasuda, H., Miyake, K., Yamazaki, H., & Hayashi, S. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.8046 · Cited by 63 · see citing works
Osteoprotegerin ligand regulates osteoclast adherence to the bone surface in mouse calvaria.
O'Brien, E. A., Williams, J. H. H., & Marshall, M. J. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3129 · Cited by 61 · see citing works
TRANCE–RANK, a New Signal Pathway Involved in Lymphocyte Development and T Cell Activation
Green, E. A., & Flavell, R. A. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.7.1017 · Cited by 59 · see citing works
Indian Hedgehog in the Late-Phase Differentiation in Mouse Chondrogenic EC Cells, ATDC5: Upregulation of Type X Collagen and Osteoprotegerin Ligand mRNAs
Akiyama, H., Shigeno, C., Iyama, K.-I., et al. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0494 · Cited by 49 · see citing works
Role of Ascorbic Acid in the Osteoclast Formation: Induction of Osteoclast Differentiation Factor with Formation of the Extracellular Collagen Matrix
Otsuka, E., Kato, Y., Hirose, S., & Hagiwara, H. (2000) · Endocrinology · doi:10.1210/endo.141.8.7597 · Cited by 47 · see citing works
Osteoblast Maturation Suppressed Osteoclastogenesis in Coculture with Bone Marrow Cells
Deyama, Y., Takeyama, S., Koshikawa, M., Shirai, Y., Yoshimura, Y., Nishikata, M., Suzuki, K., & Matsumoto, A. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3127 · Cited by 39 · see citing works
Relationship between the ability to support differentiation of osteoclast-like cells and adipogenesis in murine stromal cells derived from bone marrow
Sakaguchi, K., Morita, I., & Murota, S. (2000) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1054/plef.2000.0161 · Cited by 36 · see citing works
Sequential requirements for SCL/tal-1, GATA-2, macrophage colony-stimulating factor, and osteoclast differentiation factor/osteoprotegerin ligand in osteoclast development
Yamane, T., Kunisada, T., Yamazaki, H., Nakano, T., Orkin, S. H., & Hayashi, S. (2000) · Experimental Hematology · doi:10.1016/s0301-472x(00)00175-2 · Cited by 35 · see citing works
Effects of ageing on proliferative ability, and the expressions of secreted protein, acidic and rich in cysteine (SPARC) and osteoprotegerin (osteoclastogenesis inhibitory factor) in cultures of human periodontal ligament cells
Shiba, H., Nakanishi, K., Sakata, M., Fujita, T., Uchida, Y., & Kurihara, H. (2000) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(00)00140-8 · Cited by 31 · see citing works
Cloning and characterization of the gene encoding mouse osteoclast differentiation factor
Kodaira, K., Kodaira, K., Mizuno, A., Yasuda, H., Shima, N., Murakami, A., Ueda, M., & Higashio, K. (1999) · Gene · doi:10.1016/s0378-1119(99)00025-6 · Cited by 29 · see citing works
Basic Fibroblast Growth Factor Inhibits Osteoclast Formation Induced by 1α,25-Dihydroxyvitamin D3 through Suppressing the Production of Osteoclast Differentiation Factor
Nakagawa, N., Yasuda, H., Yano, K., Mochizuki, S.-I., Kobayashi, N., Fujimoto, H., Yamaguchi, K., Shima, N., Morinaga, T., & Higashio, K. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1621 · Cited by 13 · see citing works
The effects of interferon-beta treatment of synovial inflammation and expression of metalloproteinases in patients with rheumatoid arthritis
Gravellese (2000) · Pure Amsterdam UMC · doi:10.1002/1529-0131(200002)43:2 · Cited by 2 · see citing works
Reply
Romas (2000) · Pure Amsterdam UMC · doi:10.1002/1529-0131(200004)43:4

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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
Osteoclasts: What Do They Do and How Do They Do It?
Teitelbaum, S. L. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.060834 · Cited by 730 · see citing works
Paget disease of bone.
Roodman, G. D., & Windle, J. J. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24281 · Cited by 340 · see citing works
RANKL/RANK/OPG Pathway: A Mechanism Involved in Exercise-Induced Bone Remodeling
Tobeiha, M., Moghadasian, M. H., Amin, N., & Jafarnejad, S. (2020) · BioMed Research International · doi:10.1155/2020/6910312 · Cited by 309 · see citing works
Circulating Osteoprotegerin and Receptor Activator for Nuclear Factor κB Ligand: Clinical Utility in Metabolic Bone Disease Assessment
Rogers, A., & Eastell, R. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0794 · Cited by 215 · see citing works
Circulating estradiol and osteoprotegerin as determinants of bone turnover and bone density in postmenopausal women.
Rogers, A., Saleh, G., Hannon, R. A., Greenfield, D., & Eastell, R. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2002-020396 · Cited by 200 · see citing works
Disabling of receptor activator of nuclear factor-κB (RANK) receptor complex by novel osteoprotegerin-like peptidomimetics restores bone loss in vivo.
Cheng, X., Kinosaki, M., Takami, M., Choi, Y., Zhang, H., & Murali, R. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309690200 · Cited by 92 · see citing works
Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios.
J�rgensen, H. L., Kusk, P., Madsen, B., Fenger, M., & Lauritzen, J. B. (2004) · Journal of Bone and Mineral Metabolism · doi:10.1007/s00774-003-0461-3 · Cited by 85 · see citing works
Increased expression of IL-6 and RANK mRNA in human trabecular bone from fragility fracture of the femoral neck.
Tsangari, H., Findlay, D. M., Kuliwaba, J. S., Atkins, G. J., & Fazzalari, N. L. (2004) · Bone · doi:10.1016/j.bone.2004.02.006 · Cited by 69 · see citing works
Osteoprotegerin and the receptor activator of NF-kappa B ligand in the serum and synovial fluid. A comparison of patients with longstanding rheumatoid arthritis and osteoarthritis
Skoumal, M., Kolarz, G., Haberhauer, G., Woloszczuk, W., Hawa, G., & Klingler, A. (2005) · Rheumatology International · doi:10.1007/s00296-004-0579-1 · Cited by 66 · see citing works
Osteoprotegerin treatment impairs remodeling and apparent material properties of callus tissue without influencing structural fracture strength.
Ulrich-Vinther, M., & Andreassen, T. T. (2005) · Calcified Tissue International · doi:10.1007/s00223-004-0126-9 · Cited by 46 · see citing works
Prolactin blocks the expression of receptor activator of nuclear factor κB ligand and reduces osteoclastogenesis and bone loss in murine inflammatory arthritis
Ledesma-Colunga, M. G., Adán, N., Ortiz, G., Solís-Gutiérrez, M., López-Barrera, F., Martínez de la Escalera, G., & Clapp, C. (2017) · Arthritis Research & Therapy · doi:10.1186/s13075-017-1290-4 · Cited by 40 · 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
Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that zoledronic acid inhibits prostate cancer in bone by indirect mechanisms
Quinn, J. E., Brown, L. G., Zhang, J., Keller, E. T., Vessella, R. L., & Corey, E. (2005) · Prostate Cancer and Prostatic Diseases · doi:10.1038/sj.pcan.4500815 · Cited by 29 · see citing works
Circulating osteoprotegerin in women during GnRH-agonist treatment and their relationships with mineral components and biomarkers of bone turnover
Uemura, H., Yasui, T., Umino, Y., Niki, H., Takikawa, M., Saito, S., Furumoto, H., & Irahara, M. (2003) · Bone · doi:10.1016/j.bone.2003.08.001 · Cited by 7 · see citing works

Expression profile of osteoprotegerin, RANK and RANKL genes in the femoral head of patients with avascular necrosis
Samara, S., Dailiana, Z. H., Chassanidis, C., Koromila, T., Papatheodorou, L. K., Malizos, Κ. Ν., & Κollia, P. (2013) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2013.10.014 · Cited by 37 · see citing works
Rank/Rankl/opg: literature review.
(2011) · PubMed · Cited by 170 · see citing works
Receptor activator of nuclear factor-κB ligand (RANKL)/RANK/osteoprotegerin system in bone and other tissues (Review)
Liu, W. X., & Zhang, X. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3152 · Cited by 218 · see citing works
Effects of osteoprotegerin, RANK and RANKL on bone destruction and collapse in avascular necrosis femoral head.
Xiong, M., Liu, L.-Q., Liu, S.-Q., Liu, Z., & Gao, H. (2016) · Europe PMC (PubMed Central) · Cited by 11 · see citing works
Expression Profiles of Receptor Activator of Nuclear Factor κB Ligand, Receptor Activator of Nuclear Factor κB, and Osteoprotegerin Messenger RNA in Aged and Ovariectomized Rat Bones
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Authors: Hofbauer, L. C., & Heufelder, A. E.
Affiliations: Philipps University of Marburg (DE)
ORCID: Hofbauer, Lorenz C.
Venue: Journal of Molecular Medicine
Publisher: Springer Science and Business Media LLC
Published: 2001-05-03
Volume: 79
Issue: 5-6
Pages: 243-253
ISSN: 0946-2716 (ISSN-L)
1432-1440
DOI: 10.1007/s001090100226
OpenAlex: W2121778907
Cited by: 586
References: 130
Citations by year: 2026: 7 · 2025: 20 · 2024: 12 · 2023: 10 · 2022: 15 · 2021: 22 · 2020: 25 · 2019: 10 · 2018: 15 · 2017: 21 · 2016: 17 · 2015: 23 · 2014: 27 · 2013: 23 · 2012: 27
FWCI: 9.66
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Journal of Molecular Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
Keywords: RANKL, RANK, osteoprotegerin, RANKL/OPG system, osteoclastogenesis, bone resorption, bone loss, NF-κB signaling, Akt signaling, c-Jun, osteoporosis, osteopetrosis, postmenopausal osteoporosis, rheumatoid arthritis, Paget's disease, periodontal disease, bone metastasis, hypercalcemia of malignancy, vascular calcification, mammary gland development, calcium metabolism, metabolic bone disease
MeSH terms: Animals, Bone and Bones, Bone Diseases, Carrier Proteins, Cell Differentiation, Glycoproteins, Humans, Membrane Glycoproteins, Apoptosis, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology

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