title: Suppression of autophagy in osteocytes does not modify the adverse effects of glucocorticoids on cortical bone.
abstract: Glucocorticoid excess decreases bone mass and strength in part by acting directly on osteoblasts and osteocytes, but the mechanisms remain unclear. Macroautophagy (herein referred to as autophagy) is a lysosome-based recycling pathway that promotes the turnover of intracellular components and can promote cell function and survival under stressful conditions. Recent studies have shown that glucocorticoids stimulate autophagy in osteocytes, suggesting that autophagy may oppose the negative actions of glucocorticoids on this cell type. To address this possibility, we compared the impact of prednisolone administration on the skeletons of adult mice in which autophagy was suppressed in osteocytes, via deletion of Atg7 with a Dmp1-Cre transgene, to their control littermates. In control mice, prednisolone increased autophagic flux in osteocyte-enriched bone as measured by LC3 conversion, but this change did not occur in the mice lacking Atg7 in osteocytes. Nonetheless, prednisolone reduced femoral cortical thickness, increased cortical porosity, and reduced bone strength to similar extents in mice with and without autophagy in osteocytes. Prednisolone also suppressed osteoblast number and bone formation in the cancellous bone of control mice. As shown previously, Atg7 deletion in osteocytes reduced osteoblast number and bone formation in cancellous bone, but these parameters were not further reduced by prednisolone administration. In cortical bone, prednisolone elevated osteoclast number to a similar extent in both genotypes. Taken together, these results demonstrate that although glucocorticoids stimulate autophagy in osteocytes, suppression of autophagy in this cell type does not worsen the negative impact of glucocorticoids on the skeleton.
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
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, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
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, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
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, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors.forename: Yiying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Almeida
authors.affiliation: Department of Biostatistics, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
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, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Weinstein
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.
authors.forename: Stavros C
authors.initials: SC
authors.lastname: Manolagas
authors.affiliation: Center for Osteoporosis and Metabolic Bone Diseases, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Central Arkansas Veterans Healthcare System, Little Rock, AR, USA. Electronic address: caobrien@uams.edu.
authors.forename: Charles A
authors.initials: CA
authors.lastname: O'Brien
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D005938:Glucocorticoids / Q000009:adverse effects* / Q000378:metabolism*; D015151:Immunoblotting; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010011:Osteocytes / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055114:X-Ray Microtomography
chemical_list: D005938:Glucocorticoids
keywords: Autophagy; Glucocorticoids; Osteocytes