The effects of mitochondrial damages under stress or during aging on osteocytes networks homeostasis

Using oligomycin A-treated MLO-Y4 cells and primary murine aging osteocytes as a model of cells with mitochondrial dysfunction, it is demonstrated that when mitochondria are damaged, osteocytes tend to release signaling compounds including adenosine diphosphate. We identified that the nucleotide membrane receptors P2Y2 and P2Y6 transduced the ADP signal to Mfn2, a critical regulator of osteocyte mitochondrial transfer. Whole RNA sequencing (RNA-seq) analysis of mouse cortical bone showed that mitochondrial metabolism is impaired in aged osteocytes, and there are more extracellular nucleotides released into the matrix in cortical bone in aged mice as compared to that in young mice. Aging decreases expression levels of P2Y2/P2Y6 and Mfn2. Overall design: This study profiled the transcriptional changes of osteocytes during aging or under stress conditions.