Bone Abstracts

Although estrogen deficiency has been considered for a long time as the main factor leading to osteoporosis (OP), several lines of evidence highlight the role of oxidative stress increase with age as a key factor in this pathology. Autophagy acts as a central mechanism allowing damaged macromolecules and organelles to be degraded and recycled, such as mitochondria, the main source of reactive oxygen species (ROS). Recent publications have shown that autophagy is a new actor in OB function, specifically through its effect on lowering oxidative stress. In parallel, a decrease of autophagy with age has been reported in several cell types. Thus, we could hypothesize that an age related autophagy deficiency in OB could contribute to skeletal ageing in osteoporosis onset. In the present work, we have analyzed autophagy activity in osteocytes (OST) and OB in male and female mice according to their age and hormonal status.

In OST, we observed a decrease in autophagy with ageing while it increases following gonadectomy in males and females. However, although a 70% decrease in autophagy is observed in OB derived from ageing females, this activity remains unchanged in males. While ovariectomy has no effect on OB autophagy levels, orchidectomy leads to a four-fold increase in these cells. These results have been obtained by measuring the LC3-II protein levels in western blots and confirmed by transmission electron microscopy analysis of the autophagic vacuoles. Moreover, we observed an inverse correlation between autophagy and the oxidative stress level in OB derived from males or females.

Thus, our results suggest that OB autophagy levels fluctuate with age and hormonal status in a different way depending on the gender. In females, the lowering of autophagy in OB, which is associated with an increased oxidative stress, could play a role in the construction-resorption balance disequilibrium observed in osteoporosis.