Microporosity in mice lacking peripheral circadian clocks in osteocytes

Night and rotating shift workers display an increased incidence of hip and wrist fractures. The existence of clock genes in bone cells, identification of rhythmic oscillation of osteocyte-specific genes Sost and Dkk1, and time-dependent tissue level response to in vivo mouse tibial loading supports the notion of circadian control on bone (Bouchard et al. 2020). We have recently shown that disruption of Bmal1, and thus ablation of the circadian clock, in osteocytes resulted in greater cortical bone mass at the tibial mid-diaphysis and a reduced mechano-adaptive response in female mice. In addition to examining molecular mechanism(s) in these osteocyte-conditional knockout (OcKO) mice, we will test whether disruption of peripheral clocks in bone cells (osteocytes) of mice leads to altered cortical porosity, including lacunae and vascular channels. Specifically we will study the density (number per bone volume), spatial arrangement and relation to loading history (tension version compres