Osteocyte Dendrites: How Do They Grow, Mature, and Degenerate in Mineralized Bone?

Osteocytes, the most abundant bone cells, form an extensive cellular network via interconnecting dendrites. Like neurons in the brain, the long-lived osteocytes perceive mechanical and biological inputs and signal to other effector cells, leading to the homeostasis and turnover of bone tissues. Despite the appreciation of osteocytes' vital roles in bone biology, the initiation, growth, maintenance, and eventual degradation of osteocyte dendrites are poorly understood due to their full encasement by mineralized matrix. With the advancement of imaging modalities and genetic models, the architectural organization and molecular composition of the osteocyte dendrites, as well as their morphological changes with aging and diseases, have begun to be revealed. However, several long-standing mysteries remain unsolved, including (1) how the dendrites are initiated and elongated when a surface osteoblast becomes embedded as an osteocyte; (2) how the dendrites maintain a relatively stable morphology during their decades-long life span; (3) what biological processes control the dendrite morphology, connectivity, and stability; and (4) if these processes are influenced by age, sex, hormones, and mechanical loading. Our review of long, thin actin filament (F-actin)-containing processes extending from other cells leads to a working model that serves as a starting point to investigate the formation and maintenance of osteocyte dendrites and their degradation with aging and diseases.