Regulation of osteoclast function and bone mass by RAGE

Zheng Zhou, David Immel, Cai Xia Xi, Angelika Bierhaus, Xu Feng, Lin Mei, Peter Nawroth, David M. Stern, Wen Cheng Xiong

Research output: Contribution to journalArticle

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Abstract

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin superfamily that has multiple ligands and is implicated in the pathogenesis of various diseases, including diabetic complications, neurodegenerative disorders, and inflammatory responses. However, the role of RAGE in normal physiology is largely undefined. Here, we present evidence for a role of RAGE in osteoclast maturation and function, which has consequences for bone remodeling. Mice lacking RAGE had increased bone mass and bone mineral density and decreased bone resorptive activity in vivo. In vitro-differentiated RAGE-deficient osteoclasts exhibited disrupted actin ring and sealing zone structures, impaired maturation, and reduced bone resorptive activity. Impaired signaling downstream of αvβ3 integrin was observed in RAGE-/- bone marrow macrophages and precursors of OCs. These results demonstrate a role for RAGE in osteoclast actin cytoskeletal reorganization, adhesion, and function, and suggest that the osteosclerotic-like phenotype observed in RAGE knockout mice is due to a defect in osteoclast function.

Original languageEnglish (US)
Pages (from-to)1067-1080
Number of pages14
JournalJournal of Experimental Medicine
Volume203
Issue number4
DOIs
StatePublished - Apr 17 2006

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Osteoclasts
Bone and Bones
Actins
Bone Remodeling
Diabetes Complications
Knockout Mice
Integrins
Neurodegenerative Diseases
Bone Density
Advanced Glycosylation End Product-Specific Receptor
Immunoglobulins
Bone Marrow
Macrophages
Ligands
Phenotype

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Zhou, Z., Immel, D., Xi, C. X., Bierhaus, A., Feng, X., Mei, L., ... Xiong, W. C. (2006). Regulation of osteoclast function and bone mass by RAGE. Journal of Experimental Medicine, 203(4), 1067-1080. https://doi.org/10.1084/jem.20051947

Regulation of osteoclast function and bone mass by RAGE. / Zhou, Zheng; Immel, David; Xi, Cai Xia; Bierhaus, Angelika; Feng, Xu; Mei, Lin; Nawroth, Peter; Stern, David M.; Xiong, Wen Cheng.

In: Journal of Experimental Medicine, Vol. 203, No. 4, 17.04.2006, p. 1067-1080.

Research output: Contribution to journalArticle

Zhou, Z, Immel, D, Xi, CX, Bierhaus, A, Feng, X, Mei, L, Nawroth, P, Stern, DM & Xiong, WC 2006, 'Regulation of osteoclast function and bone mass by RAGE', Journal of Experimental Medicine, vol. 203, no. 4, pp. 1067-1080. https://doi.org/10.1084/jem.20051947
Zhou, Zheng ; Immel, David ; Xi, Cai Xia ; Bierhaus, Angelika ; Feng, Xu ; Mei, Lin ; Nawroth, Peter ; Stern, David M. ; Xiong, Wen Cheng. / Regulation of osteoclast function and bone mass by RAGE. In: Journal of Experimental Medicine. 2006 ; Vol. 203, No. 4. pp. 1067-1080.
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