Autophagy is the major catabolic process of eukaryotic cells that degrades and recycles damaged macromolecules and organelles. During this process, the cytoplasmic material targeted to degradation is delivered to lysosomes upon sequestration within double-membraned vesicles called autophagosomes. Autophagosomes and their contents are cleared upon fusing with late endosomes or lysosomes, and products of these catabolic reactions can then re-enter anabolic and/or bioenergetic metabolisms. Autophagy occurs at low level in all cells to ensure the homeostatic turnover of long-lived proteins and organelles and is upregulated under stressful conditions. In the present work, we analysed the role of autophagy in osteoblasts (OB). We first show that the autophagic process is induced in OB during mineralisation. Then, using knockdown of autophagy-essential genes and OB-specific autophagy-deficient mice, we demonstrate that autophagy deficiency reduces mineralisation capacity. Moreover, our data suggest that autophagic vacuoles are used as vehicles in OB to secrete hydroxyapatite crystals. In addition, autophagy-deficient OB exhibit increased oxidative stress and receptor activator of NF-kB (RANKL) secretion, favouring generation of osteoclasts (OC), the cells specialised in bone resorption. In vivo, we observed a 50% reduction in trabecular bone mass in OB-specific autophagy-deficient mice. Taken together, our results show for the first time that autophagy in OB is involved both in the mineralisation process and in bone homeostasis. These findings are of importance for mineralised tissues which extends from corals to vertebrates and uncovers new therapeutics targets for calcified tissue related metabolic pathologies such as osteoporosis.
Disclosure: The authors declared no competing interests. This work was supported by grants from CNRS, CEA, The Societe Francaise de Rhumatologie, and Les Anges de Verre.