Sex-specific autophagy modulation in osteoblastic lineage: a critical function to counteract bone loss in female

Autor: Véronique Breuil, Chantal Cros, Georges F. Carle, Sabine Santucci-Darmanin, Dominique Heymann, Valérie Pierrefite-Carle, Laurence Cailleteau, Sophie Pagnotta, Olivier Camuzard, Séverine Battaglia, Patricia Panaia-Ferrari, Tatiana Gritsaenko
Přispěvatelé: Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Service de rhumatologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Université Côte d'Azur, Centre Commun de Microscopie Appliquée (CCMA), Plateforme Imagerie PICMI, Institute for Research on Cancer and Aging, Nice (IRCAN), INSERM, U1081, CNRS UMR 7284, Nice, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), maurice, sandrine, Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), Service de Chirurgie Réparatrice et de la Main [CHU de Nice], Centre Hospitalier Universitaire de Nice (CHU de Nice), Centre Commun de Microscopie Appliquée [Nice] (CCMA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Plateforme Imagerie IRCAN [Nice], Université de Nice Sophia-Antipolis (UNSA), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN), Laboratoire de Biochimie [CHU Nice], Department of Oncology and Metabolism [Sheffield, UK] (European Associated Laboratory 'Sarcoma Research Unit'), The University of Sheffield [Sheffield, U.K.], This work was supported by the Commissariat à l’Energie Atomique et aux énergies alternatives (CEA) and the Société Française de Rhumatologie (SFR)., Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Universitaire de Nice (CHU Nice)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
autophagy
medicine.drug_class
[SDV]Life Sciences [q-bio]
Osteoporosis
osteocyte
Nice
Osteocytes
03 medical and health sciences
Mice
Research Paper: Gerotarget (Focus on Aging)
Internal medicine
Bone cell
Cellular catabolic process
Medicine
Animals
health care economics and organizations
computer.programming_language
[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
Sex Characteristics
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
Osteoblasts
business.industry
Gerotarget
Autophagy
aging
medicine.disease
osteoporosis
3. Good health
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Oncology
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
Estrogen
Osteocyte
osteoblast
Critical function
Female
business
computer
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Zdroj: Oncotarget
Oncotarget, Impact journals, 2016, 7 (41), pp.66416-66428. ⟨10.18632/oncotarget.12013⟩
Oncotarget, 2016, 7 (41), pp.66416-66428. ⟨10.18632/oncotarget.12013⟩
ISSN: 1949-2553
Popis: // Olivier Camuzard 1,2 , Sabine Santucci-Darmanin 1 , Veronique Breuil 1,3 , Chantal Cros 1 , Tatiana Gritsaenko 1 , Sophie Pagnotta 4 , Laurence Cailleteau 5 , Severine Battaglia 6 , Patricia Panaia-Ferrari 7 , Dominique Heymann 6,8 , Georges F. Carle 1 and Valerie Pierrefite-Carle 1 1 UMR E-4320 TIRO-MATOs CEA/DRF/BIAM, Universite Nice Sophia Antipolis, Faculte de Medecine Nice, Nice, France 2 Service de Chirurgie Reparatrice et de la Main, CHU de Nice, Nice, France 3 Service de Rhumatologie, CHU de Nice, Nice, France 4 Centre Commun de Microscopie Appliquee, Universite Nice Sophia Antipolis, Nice, France 5 Plateforme Imagerie IRCAN, Faculte de Medecine, Universite Nice Sophia Antipolis, Nice, France 6 INSERM UMR 957 Universite de Nantes, Equipe labellisee Ligue Nationale Contre le Cancer, Nantes, France 7 Laboratoire de Biochimie, CHU de Nice, Nice, France 8 Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK Correspondence to: Valerie Pierrefite-Carle, email: // Keywords : osteoblast, osteocyte, autophagy, osteoporosis, aging, Gerotarget Received : July 20, 2016 Accepted : September 09, 2016 Published : September 13, 2016 Abstract Age-related bone loss is associated with an increased oxidative stress which is worsened by estrogen fall during menauposis. This observation has drawn attention to autophagy, a major cellular catabolic process, able to alleviate oxidative stress in osteoblasts (OB) and osteocytes (OST), two key bone cell types. Moreover, an autophagy decline can be associated with aging, suggesting that an age-related autophagy deficiency in OB and/or OST could contribute to skeletal aging and osteoporosis onset. In the present work, autophagy activity was analyzed in OST and OB in male and female mice according to their age and hormonal status. In OST, autophagy decreases with aging in both sexes. In OB, although a 95% decrease in autophagy is observed in OB derived from old females, this activity remains unchanged in males. In addition, while ovariectomy has no effect on OB autophagy levels, orchidectomy appears to stimulate this process. An inverse correlation between autophagy and the oxidative stress level was observed in OB derived from males or females. Finally, using OB-specific autophagy-deficient mice, we showed that autophagy deficiency aggravates the bone loss associated with aging and estrogen deprivation. Taken together, our data indicate that autophagic modulation in bone cells differs according to sex and cell type. The lowering of autophagy in female OB, which is associated with an increased oxidative stress, could play a role in osteoporosis pathophysiology and suggests that autophagy could be a new therapeutic target for osteoporosis in women.
Databáze: OpenAIRE