The DOI matches its Crossref record; 18 of the 18 references it cites were found in a registry or an index.
The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone Resorption
Abstract
Although multiple hormones and cytokines regulate various aspects of osteoclast formation, the final two effectors are osteoprotegerin ligand (OPG-L)/osteoclast differentiation factor (ODF), a recently cloned member of the tumor necrosis factor superfamily, and macrophage colony–stimulating factor. OPG-L/ODF is produced by osteoblast lineage cells and exerts its biological effects through binding to its receptor, osteoclast differentiation and activation receptor (ODAR)/receptor activator of NF-κB (RANK), on osteoclast lineage cells, in either a soluble or a membrane-bound form, the latter of which requires cell-to-cell contact. Binding results in rapid differentiation of osteoclast precursors in bone marrow to mature osteoclasts and, at higher concentrations, in increased functional activity and reduced apoptosis of mature osteoclasts. The biological activity of OPG-L/ODF is neutralized by binding to osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor (OCIF), a member of the TNF-receptor superfamily that also is secreted by osteoblast lineage cells. The biological importance of this system is underscored by the induction in mice of severe osteoporosis by targeted ablation of OPG/OCIF and by the induction of osteopetrosis by targeted ablation of OPG-L/ODF or overexpression of OPG/OCIF. Thus, osteoclast formation may be determined principally by the relative ratio of OPG-L/ODF to OPG/OCIF in the bone marrow microenvironment, and alterations in this ratio may be a major cause of bone loss in many metabolic disorders, including estrogen deficiency and glucocorticoid excess. That changes in but two downstream cytokines mediate the effects of large numbers of upstream hormones and cytokines suggests a regulatory mechanism for osteoclastogenesis of great efficiency and elegance.
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Citations
Cites
OPGL is a key regulator of osteoclastogenesis, lymphocyte development and lymph node organogenesis.
Kong, Y.-Y., Yoshida, H., Sarosi, I., Tan, H.-L., Timms, E., Capparelli, C., Morony, S., Oliveira-dos-Santos, A. J., Van, G., Itie, A., et al. (1999) · Nature · doi:10.1038/16852 · Cited by 3,351
Self-citationHsu, H., Lacey, D. L., Dunstan, C. R., Solovyev, I., Colombero, A., Timms, E., Tan, H.-L., Elliott, G., Kelley, M. J., Sarosi, I., et al. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.7.3540 · Cited by 1,636
Self-citationYasuda, 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
Estrogen promotes apoptosis of murine osteoclasts mediated by TGF–β
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“(74–79)Estrogen deficiency also increases activation(80) and decreases apoptosis (81) of mature osteoclasts, and these effects are also reversed by estrogen.”
BackgroundHofbauer, L. C., Gori, F., Riggs, B. L., Lacey, D. L., Dunstan, C. R., Spelsberg, T. C., & Khosla, S. (1999) · Endocrinology · doi:10.1210/endo.140.10.7034 · Cited by 794
Self-citationSevere osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin.
Mizuno, A., Amizuka, N., Irie, K., Murakami, A., Fujise, N., Kanno, T., Sato, Y., Nakagawa, N., Yasuda, H., Mochizuki, S.-I., et al. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.8697 · Cited by 775
RANK Is the Essential Signaling Receptor for Osteoclast Differentiation Factor in Osteoclastogenesis
Nakagawa, N., Kinosaki, M., Yamaguchi, K., Shima, N., Yasuda, H., Yano, K., Morinaga, T., & Higashio, K. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9788 · Cited by 746
Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis
Pacifici, R. (1996) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.5650110802 · Cited by 741
Hofbauer, L. C., Khosla, S., Dunstan, C. R., Lacey, D. L., Spelsberg, T. C., & Riggs, B. L. (1999) · Endocrinology · doi:10.1210/endo.140.9.7131 · Cited by 692
Self-citationThe ligand for osteoprotegerin (OPGL) directly activates mature osteoclasts.
Burgess, T. L., Qian, Y.-X., Kaufman, S., Ring, B. D., Van, G., Capparelli, C., Kelley, M., Hsu, H., Boyle, W. J., Dunstan, C. R., et al. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.145.3.527 · Cited by 689
Self-citation
Cited by
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670
Self-citationSex Steroids and the Construction and Conservation of the Adult Skeleton
Riggs, B. L., Khosla, S., & Melton, L. J. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.3.0465 · Cited by 1,846
Self-citationCellular and molecular mechanisms of bone remodeling
Raggatt, L. J., & Partridge, N. C. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.r109.041087 · Cited by 1,402
Li, J., Sarosi, I., Yan, X.-Q., Morony, S., Capparelli, C., Tan, H.-L., McCabe, S., Elliott, R., Scully, S., Van, G., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1566 · Cited by 1,119
Self-citationChanges in Proinflammatory Cytokine Activity after Menopause
Pfeilschifter, J., Köditz, R., Pfohl, M., & Schatz, H. (2002) · Endocrine Reviews · doi:10.1210/edrv.23.1.0456 · Cited by 914
Metadata
- Authors
- Hofbauer, L. C., Khosla, S., Dunstan, C. R., Lacey, D. L., Boyle, W. J., & Riggs, B. L.
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-01-01
- Volume
- 15
- Issue
- 1
- Pages
- 2-12
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W2063048904
- Cited by
- 1,173
- References
- 18
- FWCI
- 29.85
- Type
- journal article
- Language
- en
- Open access
- closed
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- Hofbauer, L. C., Khosla, S., Dunstan, C. R., Lacey, D. L., Boyle, W. J., & Riggs, B. L. (2000). The Roles of Osteoprotegerin and Osteoprotegerin Ligand in the Paracrine Regulation of Bone Resorption. Journal of Bone and Mineral Research. https://doi.org/10.1359/jbmr.2000.15.1.2
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