title: 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.
authors: *Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Ontario, Canada; and Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
authors: Hongwei
authors: H
authors: Jiang
authors: *Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Ontario, Canada; and Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
authors: Yongqiang
authors: Y
authors: Wang
authors: *Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Ontario, Canada; and Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
authors: Ana
authors: A
authors: Viniegra
authors: *Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Ontario, Canada; and Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
authors: Corneliu
authors: C
authors: Sima
authors: *Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Ontario, Canada; and Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
authors: Christopher A
authors: CA
authors: McCulloch
authors: *Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Ontario, Canada; and Department of Operative Dentistry and Endodontics, Guanghua School of Stomatology, Sun Yat-sen University, and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China michael.glogauer@utoronto.ca.
authors: Michael
authors: M
authors: Glogauer
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D016301:Alveolar Bone Loss / Q000235:genetics / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D036681:Fluorescence Recovery After Photobleaching; D018260:Gelsolin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010510:Periodontal Diseases / Q000235:genetics / Q000503:physiopathology*; D014162:Transfection
chemical_list: D018260:Gelsolin; C065395:scinderin
keywords: actin; bone resorption; fusion; osteoclastogenesis