title: Low bone mass and changes in the osteocyte network in mice lacking autophagy in the osteoblast lineage.
abstract: Autophagy maintains cell function and homeostasis by recycling intracellular components. This process is also required for morphological changes associated with maturation of some cell types. Osteoblasts are bone forming cells some of which become embedded in bone and differentiate into osteocytes. This transformation includes development of long cellular projections and a reduction in endoplasmic reticulum and mitochondria. We examined the role of autophagy in osteoblasts by deleting Atg7 using an Osterix1-Cre transgene, which causes recombination in osteoblast progenitors and their descendants. Mice lacking Atg7 in the entire osteoblast lineage had low bone mass and fractures associated with reduced numbers of osteoclasts and osteoblasts. Suppression of autophagy also reduced the amount of osteocyte cellular projections and led to retention of endoplasmic reticulum and mitochondria in osteocytes. These results demonstrate that autophagy in osteoblasts contributes to skeletal homeostasis and to the morphological changes associated with osteocyte formation.
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.|Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
authors.forename: Marilina
authors.initials: M
authors.lastname: Piemontese
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.|Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
authors.forename: Melda
authors.initials: M
authors.lastname: Onal
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.|Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
authors.forename: Jinhu
authors.initials: J
authors.lastname: Xiong
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.|Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
authors.forename: Li
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.
authors.forename: Jeff D
authors.initials: JD
authors.lastname: Thostenson
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.|Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
authors.forename: Maria
authors.initials: M
authors.lastname: Almeida
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States of America.|Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, United States of America.
authors.forename: Charles A
authors.initials: CA
authors.lastname: O'Brien
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D001343:Autophagy; D000071193:Autophagy-Related Protein 7 / Q000172:deficiency / Q000235:genetics; D015519:Bone Density; D001854:Bone Marrow Cells / Q000166:cytology; D016723:Bone Remodeling; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000502:physiology*; D002374:Catalase / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D050723:Fractures, Bone / Q000209:etiology; D051379:Mice; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010011:Osteocytes / Q000166:cytology* / Q000378:metabolism; D010012:Osteogenesis; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C502661:Atg7 protein, mouse; D017382:Reactive Oxygen Species; D002374:Catalase; D000071193:Autophagy-Related Protein 7