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Adseverin plays a role in osteoclast differentiation and periodontal disease-mediated bone loss.

Abstract
Osteoclast differentiation and function are highly dependent on the assembly and turnover of actin filaments, but little is known about the roles of actin binding proteins in these processes. Adseverin (Ads), a member of the gelsolin superfamily of actin capping and severing proteins, regulates actin filament turnover and can regulate the turnover of cortical actin filaments of chromaffin cells during exocytosis. Using a conditional Ads knockout mouse model, we confirmed our previous finding in cultured cells that Ads plays a role in osteoclastogenesis (OCG) and actin cytoskeletal organization in osteoclasts. Here we show that Ads is required for osteoclast formation and that when alveolar bone resorption is experimentally induced in mice, genetic deletion of Ads prevents osteoclast-mediated bone loss. Further, when Ads-null osteoclasts are cultured, they exhibit defective OCG, disorganized podosome-based actin filament superstructures, and decreased bone resorption. Reintroduction of Ads into Ads-null osteoclast precursor cells restored these osteoclast defects. Collectively, these data demonstrate a unique and osteoclast-specific role for Ads in OCG and osteoclast function.
AuthorsHongwei Jiang, Yongqiang Wang, Ana Viniegra, Corneliu Sima, Christopher A McCulloch, Michael Glogauer
JournalFASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 29 Issue 6 Pg. 2281-91 (Jun 2015) ISSN: 1530-6860 [Electronic] United States
PMID25681458 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© FASEB.
Chemical References
  • Gelsolin
  • scinderin
Topics
  • Actin Cytoskeleton (genetics, metabolism)
  • Alveolar Bone Loss (genetics, physiopathology)
  • Animals
  • Blotting, Western
  • Cell Differentiation (genetics, physiology)
  • Cells, Cultured
  • Fluorescence Recovery After Photobleaching
  • Gelsolin (deficiency, genetics, physiology)
  • Mice, Knockout
  • Microscopy, Confocal
  • Osteoclasts (cytology, metabolism)
  • Periodontal Diseases (genetics, physiopathology)
  • Transfection

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