BoneKEy Reports | BoneKEy Watch

Autophagy could be a factor in age-related low bone mass



DOI:10.1038/bonekey.2013.161

Mice with a conditional allele that codes for Atg7, an enzyme known to activate LC3, a ubiquitin-like protein, were used to investigate the effects of autophagy in osteocytes. The mice were crossed with transgenic mice to create a mouse strain that lacked Atg7 in osteocytes and mature osteoblasts only.

At 6 weeks after birth, the conditional knockout mice showed significantly reduced bone mass throughout the skeleton compared to controls, but normal body weight. MicroCT scanning showed that this was due to significantly lower cancellous bone volume in the femur and spine. The mice also had 50% fewer osteoclasts compared to controls and these covered a reduced area of bone surface; this led to a reduction in bone formation rate. Conditional knockout mice also showed higher levels of oxidative stress in their bones.

All of these changes are similar to those seen in aged compared to young mice, suggesting that suppressing autophagy in osteocytes has a similar impact on the skeleton to aging.

Editor’s comment: Autophagy is increasingly recognized as a major regulatory mechanism that underpins cell fate and aging. In bone, mutations in genes involved in the ubiquitination pathway—a central component of the autophagic process—have been found in people with Paget’s disease. This study shows that impaired authophagy in osteocytes inhibits bone remodeling and reduces trabecular and cortical bone mass. The mechanisms by which osteocyte autophagy controls bone turnover remain to be elucidated.


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