Osteocyte mechanobiology in aging and disease

The skeleton is a multifunctional organ system with unpredicted systemic influence. It offers far more than mere scaffolding-sites for muscle and tendon attachment-or a storage depot for calcium and phosphorus. Its remnants in the fossil record belie its strength that arises from self-organization and self-renewal. Yet, it is simultaneously elegantly sensitive to a changing mechanical and hormonal environment. Discoveries over the recent decades have identified unanticipated contributions by osteocytes to fragility with age, mineral metabolism, renal and cardiovascular function, and tumor metastasis to bone. Continued exploration advocates that the osteocyte-a terminally differentiated cell trapped within a matrix of its own making-serves as the master conductor of skeletal health. Within, we review osteocytic contributions to skeletal health, the mechanisms involved, and the capacity for both aging and disease to impede and subvert osteocyte function.