Cited by 172Bone Metabolism and DiseasesAdvanced Glycation End Products researchImmune Response and Inflammation

HMGB1 Regulates RANKL-Induced Osteoclastogenesis in a Manner Dependent on RAGE

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Zhou, Zheng, Han, Jun-Yan, Xi, Cai-Xia, Xie, Jian-Xin, Feng, Xu, Wang, Cong-Yi, Mei, Lin, Xiong, Wen-Cheng·2008·Journal of Bone and Mineral Research

Abstract

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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  • HMGB1 and M-CSF have been suggested to be produced by osteocytes that stimulate osteoclast recruitment during bone remodeling.

    “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].”

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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
Published
2008-07-01
Volume
23
Issue
7
Pages
1084-1096
ISSN
  • 0884-0431 (ISSN-L)
  • 1523-4681
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
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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