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Oncotarget. 2016 Oct 11;7(41):66416-66428. doi: 10.18632/oncotarget.12013.

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

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UMR E-4320 TIRO-MATOs CEA/DRF/BIAM, Université Nice Sophia Antipolis, Faculté de Médecine Nice, Nice, France.
Service de Chirurgie Réparatrice et de la Main, CHU de Nice, Nice, France.
Service de Rhumatologie, CHU de Nice, Nice, France.
Centre Commun de Microscopie Appliquee, Université Nice Sophia Antipolis, Nice, France.
Plateforme Imagerie IRCAN, Faculté de Médecine, Université Nice Sophia Antipolis, Nice, France.
INSERM UMR 957 Université de Nantes, Equipe labellisée Ligue Nationale Contre le Cancer, Nantes, France.
Laboratoire de Biochimie, CHU de Nice, Nice, France.
Department of Oncology and Metabolism, The Medical School, University of Sheffield, Sheffield, UK.


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.


Gerotarget; aging; autophagy; osteoblast; osteocyte; osteoporosis

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