Cited by 391Bone Metabolism and DiseasesCell death mechanisms and regulationOsteomyelitis and Bone Disorders Research

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Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo.

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Lacey, David L., Tan, Hong Lin, Lu, John, Kaufman, Steven, Van, Gwyneth, Qiu, Wanrang, Rattan, Alana, Scully, Sheila, Fletcher, Frederick, Juan, Todd, Kelley, Michael, Burgess, Teresa L., Boyle, William J., Polverino, Anthony J.·2000·The American Journal of Pathology

DOI 10.1016/s0002-9440(10)64556-7PMC PMC1850124

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Abstract

Osteoprotegerin ligand (OPGL) targets osteoclast precursors and osteoclasts to enhance differentiation and activation, however, little is known about OPGL effects on osteoclast survival. In vitro, the combination of OPGL + colony-stimulating factor-1 (CSF-1) is required for optimal osteoclast survival. Ultrastructurally, apoptotic changes were observed in detached cells and culture lysates exhibited elevated caspase 3 activity, particularly in cultures lacking CSF-1. DEVD-FMK (caspase 3 inhibitor) partially protected cells when combined with OPGL, but not when used alone or in combination with CSF-1. CSF-1 maintained NF-kappaB activation and increased the expression of bcl-2 and bcl-X(L) mRNA, but had no effect on JNK activation. In contrast, OPGL enhanced both NF-kappaB and JNK kinase activation and increased the expression of c-src, but not bcl-2 and bcl-X(L) mRNA. These data suggest that aspects of both OPGL's and CSF-1's signaling/survival pathways are required for optimal osteoclast survival. In mice, a single dose of OPG, the OPGL decoy receptor, led to a >90% loss of osteoclasts because of apoptosis within 48 hours of exposure without impacting osteoclast precursor cells. Therefore, OPGL is essential, but not sufficient, for osteoclast survival and endogenous CSF-1 levels are insufficient to maintain osteoclast viability in the absence of OPGL.

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Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
Lacey, D. L., Timms, E., Tan, H.-L., Kelley, M. J., Dunstan, C. R., Burgess, T., Elliott, R., Colombero, A., Elliott, G., Scully, S., et al. (1998) · Cell · doi:10.1016/s0092-8674(00)81569-x · Cited by 5,439
Self-citation
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
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Yasuda, H., Shima, N., Nakagawa, N., Yamaguchi, K., Kinosaki, M., Mochizuki, S.-I., Tomoyasu, A., Yano, K., Goto, M., Murakami, A., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3597 · Cited by 4,224
Molecular characterization of mitochondrial apoptosis-inducing factor
Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Snow, B. E., Brothers, G. M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., et al. (1999) · Nature · doi:10.1038/17135 · Cited by 4,060
Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo.
Walczak, H., Miller, R. E., Ariail, K., Gliniak, B., Griffith, T. S., Kubin, M., Chin, W., Jones, J., Woodward, A., Le, T., et al. (1999) · Nature Medicine · doi:10.1038/5517 · Cited by 2,497
A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function.
Anderson, D. M., Maraskovsky, E., Billingsley, W. L., Dougall, W. C., Tometsko, M. E., Roux, E. R., Teepe, M. C., DuBose, R. F., Cosman, D., & Galibert, L. (1997) · Nature · doi:10.1038/36593 · Cited by 2,290
The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene
Yoshida, H., Hayashi, S.-I., Kunisada, T., Ogawa, M., Nishikawa, S., Okamura, H., Sudo, T., Shultz, L. D., & Nishikawa, S.-I. (1990) · Nature · doi:10.1038/345442a0 · Cited by 1,789
Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand.
Hsu, 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-citation
Life, death, and the pursuit of apoptosis.Preprint
White, E. (1996) · Genes & Development · doi:10.1101/gad.10.1.1 · Cited by 1,306
Raf-1 activates MAP kinase-kinase
Kyriakis, J. M., App, H., Zhang, X., Banerjee, P. T., Brautigan, D. L., Rapp, U. R., & Avruch, J. (1992) · Nature · doi:10.1038/358417a0 · Cited by 1,263

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Kacena, M. A., Nelson, T., Clough, M. E., Lee, S., Lorenzo, J. A., Gundberg, C. M., & Horowitz, M. C. (2006) · Bone · doi:10.1016/j.bone.2006.05.004 · Cited by 83
Inhibition of bone resorption, rather than direct cytotoxicity, mediates the anti-tumour actions of ibandronate and osteoprotegerin in a murine model of breast cancer bone metastasis
Zheng, Y., Zhou, H., Brennan, K., Blair, J. M., Modzelewski, J. R. K., Seibel, M. J., & Dunstan, C. R. (2007) · Bone · doi:10.1016/j.bone.2006.09.016 · Cited by 82
The role of the bone microenvironment in skeletal metastasis
Zheng, Y., Zhou, H., Dunstan, C. R., Sutherland, R. L., & Seibel, M. J. (2012) · Journal of bone oncology · doi:10.1016/j.jbo.2012.11.002 · Cited by 87
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Yue, J., Griffith, J. F., Xiao, F., Shi, L., Wang, D., Shen, J., Wong, P. C. H., Li, E. K., Li, M., Li, T. K., et al. (2016) · Arthritis Care & Research · doi:10.1002/acr.23133 · Cited by 79
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Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis
Chiu, Y. G., & Ritchlin, C. T. (2016) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2017.1263614 · Cited by 81
Kinetics of bone protection by recombinant osteoprotegerin therapy in Lewis rats with adjuvant arthritis.
Campagnuolo, G., Bolon, B., & Feige, U. (2002) · Arthritis & Rheumatism · doi:10.1002/art.10369 · Cited by 78
RANKL-stimulated osteoclast-like cell formation in vitro is partially dependent on endogenous interleukin-1 production
Lee, S., Gardner, A. E., Kalinowski, J., Jastrzebski, S. L., & Lorenzo, J. (2005) · Bone · doi:10.1016/j.bone.2005.10.011 · Cited by 79

Authors: Lacey, D. L., Tan, H. L., Lu, J., Kaufman, S., Van, G., Qiu, W., Rattan, A., Scully, S., Fletcher, F., Juan, T., Kelley, M., Burgess, T. L., Boyle, W. J., & Polverino, A. J.
Affiliations: Amgen (United States) (US)
Corresponding author: Lacey, David L.
ORCID: Tan, Hong Lin
Kelley, Michael
Boyle, William J.
Venue: The American Journal of Pathology
Publisher: Elsevier BV
Published: 2000-08
Volume: 157
Issue: 2
Pages: 435-448
ISSN: 0002-9440 (ISSN-L)
DOI: 10.1016/s0002-9440(10)64556-7
PMC: PMC1850124
OpenAlex: W2133551420
Cited by: 391
References: 33
Citations by year: 2026: 2 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 9 · 2021: 10 · 2020: 12 · 2019: 23 · 2018: 7 · 2017: 10 · 2016: 15 · 2015: 10 · 2014: 7 · 2013: 27 · 2012: 25
FWCI: 5.17
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: American Journal Of Pathology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Rheumatology › Osteomyelitis and Bone Disorders Research
Keywords: osteoprotegerin ligand, osteoclast survival, colony-stimulating factor 1, osteoclast apoptosis, caspase-3, NF-κB activation, JNK activation, Bcl-2, Bcl-xL, Src kinase, osteoprotegerin, bone resorption, osteoclastogenesis
MeSH terms: Animals, Carrier Proteins, Cell Survival, Cells, Cultured, Gene Expression Regulation, Glycoproteins, Injections, Subcutaneous, Male, Membrane Glycoproteins, Mice, Inbred C3H, Osteoclasts, RNA, Messenger, Time Factors, Macrophage Colony-Stimulating Factor, NF-kappa B, Apoptosis, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Proto-Oncogene Proteins c-bcl-2, bcl-X Protein, Mice, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B

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Osteoprotegerin ligand modulates murine osteoclast survival in vitro and in vivo.

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