HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE

Zheng Zhou, Jun Yan Han, Caixia Xi, Jian Xin Xie, Xu Feng, Cong Yi Wang, Lin Mei, Wencheng Xiong

Research output: Contribution to journalArticle

75 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1084-1096
Number of pages13
JournalJournal of Bone and Mineral Research
Volume23
Issue number7
DOIs
StatePublished - Jul 1 2008

Fingerprint

Osteogenesis
Macrophages
Osteoclasts
Cytokines
Toll-Like Receptors
Bone Resorption
Nuclear Proteins
Actin Cytoskeleton
Integrins
Advanced Glycosylation End Product-Specific Receptor

Keywords

  • High-mobility group box 1
  • Osteoclastogenesis
  • RANKL
  • Receptor for advanced glycation endproducts

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE. / Zhou, Zheng; Han, Jun Yan; Xi, Caixia; Xie, Jian Xin; Feng, Xu; Wang, Cong Yi; Mei, Lin; Xiong, Wencheng.

In: Journal of Bone and Mineral Research, Vol. 23, No. 7, 01.07.2008, p. 1084-1096.

Research output: Contribution to journalArticle

Zhou, Z, Han, JY, Xi, C, Xie, JX, Feng, X, Wang, CY, Mei, L & Xiong, W 2008, 'HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE', Journal of Bone and Mineral Research, vol. 23, no. 7, pp. 1084-1096. https://doi.org/10.1359/jbmr.080234
Zhou, Zheng ; Han, Jun Yan ; Xi, Caixia ; Xie, Jian Xin ; Feng, Xu ; Wang, Cong Yi ; Mei, Lin ; Xiong, Wencheng. / HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE. In: Journal of Bone and Mineral Research. 2008 ; Vol. 23, No. 7. pp. 1084-1096.
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