Disrupted osteocyte connectivity and pericellular fluid flow in bone with aging and defective TGF-β signaling

Significance Bone fragility increases with age as the result of the concurrent decline of bone mass, quality, and mechanosensitivity. While the coordinated decline of these behaviors remains unexplained, the role of osteocytes in each of these processes and the age-related degeneration of the lacunocanalicular network (LCN) in which they reside implicate osteocytes in bone aging. In this work, we identify canalicular loss as a driver behind declining mass transport and mechanostimulation within the LCN of aged bone and of bone with osteocyte-intrinsic defects in transforming growth factor beta signaling. We identify the ability to restore physical stimulation to osteocytes through expansion of the pericellular space. Future studies will determine if therapeutic stimulation of osteocyte function can improve bone health with age.