原创力文档the arf tumor suppressor regulates bone remodeling and osteosarcoma development in micearf肿瘤抑制调节骨重建和小鼠骨肉瘤发展.pdfVIP
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the arf tumor suppressor regulates bone remodeling and osteosarcoma development in micearf肿瘤抑制调节骨重建和小鼠骨肉瘤发展
The ARF Tumor Suppressor Regulates Bone Remodeling
and Osteosarcoma Development in Mice
1. 1. 1 1 1
Daniel A. Rauch , Michelle A. Hurchla , John C. Harding , Hongju Deng , Lauren K. Shea , Mark C.
1 2,3 2,3 4 2
Eagleton , Stefan Niewiesk , Michael D. Lairmore , David Piwnica-Worms , Thomas J. Rosol , Jason D.
1 1 1
Weber , Lee Ratner , Katherine N. Weilbaecher *
1 Division of Molecular Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, United States of America, 2 College of
Veterinary Medicine, The Ohio State University, Columbus, Ohio, United States of America, 3 Center for Retrovirus Research, Department of Veterinary Biosciences, The
Ohio State University, Columbus, Ohio, United States of America, 4 Molecular Imaging Center, Mallinckrodt Institute of Radiology, Department of Developmental Biology,
Washington University School of Medicine, St. Louis, Missouri, United States of America
Abstract
The ARF tumor suppressor regulates p53 as well as basic developmental processes independent of p53, including osteoclast
activation, by controlling ribosomal biogenesis. Here we provide evidence that ARF is a master regulator of bone
remodeling and osteosarcoma (OS) development in mice. Arf-/- mice displayed increased osteoblast (OB) and osteoclast (OC)
activity with a significant net increase in trabecular bone volume. The long bones of Arf-/- mice had increased expression of
OB genes while Arf-/- OB showed
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