Suppression of autophagy in osteocytes mimics skeletal aging

J Biol Chem. 2013 Jun 14;288(24):17432-40. doi: 10.1074/jbc.M112.444190. Epub 2013 May 3.


Bone mass declines with age but the mechanisms responsible remain unclear. Here we demonstrate that deletion of a conditional allele for Atg7, a gene essential for autophagy, from osteocytes caused low bone mass in 6-month-old male and female mice. Cancellous bone volume and cortical thickness were decreased, and cortical porosity increased, in conditional knock-out mice compared with control littermates. These changes were associated with low osteoclast number, osteoblast number, bone formation rate, and wall width in the cancellous bone of conditional knock-out mice. In addition, oxidative stress was higher in the bones of conditional knock-out mice as measured by reactive oxygen species levels in the bone marrow and by p66(shc) phosphorylation in L6 vertebra. Each of these changes has been previously demonstrated in the bones of old versus young adult mice. Thus, these results demonstrate that suppression of autophagy in osteocytes mimics, in many aspects, the impact of aging on the skeleton and suggest that a decline in autophagy with age may contribute to the low bone mass associated with aging.

Keywords: Aging; Autophagy; Bone; Mouse; Osteocyte; Remodeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aging
  • Animals
  • Autophagy
  • Autophagy-Related Protein 7
  • Bone Density
  • Cell Differentiation
  • Cells, Cultured
  • Female
  • Femur / diagnostic imaging
  • Femur / metabolism*
  • Femur / pathology
  • Lumbar Vertebrae / diagnostic imaging
  • Lumbar Vertebrae / metabolism*
  • Lumbar Vertebrae / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins / deficiency
  • Microtubule-Associated Proteins / genetics
  • Osteoblasts / physiology
  • Osteoclasts / physiology
  • Osteocytes / physiology*
  • Oxidative Stress
  • Radiography
  • Reactive Oxygen Species / metabolism


  • Atg7 protein, mouse
  • Microtubule-Associated Proteins
  • Reactive Oxygen Species
  • Autophagy-Related Protein 7