The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE
Open accessAbstract
High-mobility group box 1 (HMGB1), a nonhistone nuclear protein, is released by macrophages into the extracellular milieu consequent to cellular activation. Extracellular HMGB1 has properties of a pro-inflammatory cytokine through its interaction with receptor for advanced glycation endproducts (RAGE) and/or toll-like receptors (TLR2 and TLR4). Although HMGB1 is highly expressed in macrophages and differentiating osteoclasts, its role in osteoclastogenesis remains largely unknown. In this report, we present evidence for a function of HMGB1 in this event. HMGB1 is released from macrophages in response to RANKL stimulation and is required for RANKL-induced osteoclastogenesis in vitro and in vivo. In addition, HMGB1, like other osteoclastogenic cytokines (e.g., TNFα), enhances RANKL-induced osteoclastogenesis in vivo and in vitro at subthreshold concentrations of RANKL, which alone would be insufficient. The role of HMGB1 in osteoclastogenesis is mediated, in large part, by its interaction with RAGE, an immunoglobin domain containing family receptor that plays an important role in osteoclast terminal differentiation and activation. HMGB1-RAGE signaling seems to be important in regulating actin cytoskeleton reorganization, thereby participating in RANKL-induced and integrin-dependent osteoclastogenesis. Taken together, these observations show a novel function of HMGB1 in osteoclastogenesis and provide a new link between inflammatory mechanisms and bone resorption.
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“High mobility group box protein 1 (HMGB1) [198–200] and M-CSF [201] have also been suggested to be produced by osteocytes that stimulate osteoclast recruitment during bone remodeling [72, 73].”
From Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells (2015) · cites this paper as [200]
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Citations
Cites
Osteoclast differentiation and activation
Boyle, W. J., Simonet, W. S., & Lacey, D. L. (2003) · Nature · doi:10.1038/nature01658 · Cited by 6,670
Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
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Release of chromatin protein HMGB1 by necrotic cells triggers inflammation
Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002) · Nature · doi:10.1038/nature00858 · Cited by 4,221
High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal
Lotze, M. T., & Tracey, K. J. (2005) · Nature reviews. Immunology · doi:10.1038/nri1594 · Cited by 2,490
Park, J. S., Svetkauskaite, D., He, Q., Kim, J., Strassheim, D., Ishizaka, A., & Abraham, E. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306793200 · Cited by 1,582
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“text, because release of HMGB1 is elicited by lipopolysaccharide and multiple inflammatory mediators (IL-1, TNF , interferon- and - ), we propose that the HMGB1–RAGE interaction could represent a final common pathway in inflammation-associated bone resorption.((9,35,39))”
BackgroundThe multiligand receptor RAGE as a progression factor amplifying immune and inflammatory responses
Schmidt, A. M., Yan, S. D., Yan, S. F., & Stern, D. M. (2001) · Journal of Clinical Investigation · doi:10.1172/jci14002 · Cited by 1,256
Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion
Bonaldi, T., Talamo, F., Scaffidi, P., Ferrera, D., Porto, A., Bachi, A., Rubartelli, A., Agresti, A., & Bianchi, M. E. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg516 · Cited by 1,252
Cholinergic agonists inhibit HMGB1 release and improve survival in experimental sepsis
Wang, H., Liao, H., Ochani, M., Justiniani, M., Lin, X., Yang, L., Al-Abed, Y., Wang, H., Metz, C., Miller, E. J., et al. (2004) · Nature Medicine · doi:10.1038/nm1124 · Cited by 1,170
Cited by
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
HMGB1 is a therapeutic target for sterile inflammation and infection
Andersson, U., & Tracey, K. J. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-030409-101323 · Cited by 1,437
“Osteoclasts Migration; enhanced osteoclastogenesis and TNF synthesis via HMGB1 interaction with the TNF promoter (80, 140)”
BackgroundCellular signalling of the receptor for advanced glycation end products (RAGE)
Xie, J., Méndez, J. D., Méndez-Valenzuela, V., & Aguilar-Hernández, M. (2013) · Cellular Signalling · doi:10.1016/j.cellsig.2013.06.013 · Cited by 525
Self-citationHyperglycemia and Glycation in Diabetic Complications
Nègre‐Salvayre, A., Salvayre, R., Augè, N., Pamplona, R., & Portero‐Otín, M. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2484 · Cited by 426
“Various signaling pathways are involved, including JNK, p38, ERK and NF-kB, PKC= pleckstrin (337, 342), as well as interactions with the Toll-like– receptor pathway, as assessed by the inhibitory effect of antibodies directed against TLR4, RAGE, and CD36 (136).”
InfluentialCalcium Phosphate Crystals Induce Cell Death in Human Vascular Smooth Muscle Cells
Ewence, A. E., Bootman, M. D., Roderick, H. L., Skepper, J. N., McCarthy, G., Epple, M., Neumann, M., Shanahan, C. M., & Proudfoot, D. (2008) · Circulation Research · doi:10.1161/circresaha.108.181305 · Cited by 325
Metadata
- Authors
- Zhou, Z., Han, J.-Y., Xi, C.-X., Xie, J.-X., Feng, X., Wang, C.-Y., Mei, L., & Xiong, W.-C.
- Affiliations
- Augusta University (US)
- University of Alabama at Birmingham (US)
- Corresponding author
- Xiong, Wen-Cheng
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-07-01
- Volume
- 23
- Issue
- 7
- Pages
- 1084-1096
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- PMC
- PMC2679382
- OpenAlex
- W2126202075
- Cited by
- 160
- References
- 43
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 8 · 2021: 12 · 2020: 14 · 2019: 15 · 2018: 8 · 2017: 8 · 2016: 11 · 2015: 7 · 2014: 6 · 2013: 16 · 2012: 5
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR048120, AR048120)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- HMGB1, RANKL, osteoclastogenesis, RAGE, receptor for advanced glycation end products, macrophages, bone resorption, actin cytoskeleton remodeling, integrin signaling, inflammatory bone loss, extracellular HMGB1
- MeSH terms
- Receptor for Advanced Glycation End Products, Animals, Base Sequence, Cell Division, Fluorescent Antibody Technique, Osteoclasts, Receptors, Immunologic, Blotting, Western, DNA Primers, Mice, Knockout, HMGB1 Protein, Mice, RANK Ligand
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