Mechanically induced Ca oscillations in osteocytes release extracellular vesicles and enhance bone formation.

The vast osteocytic network is believed to orchestrate bone metabolic activity in response to mechanical stimuli through production of sclerostin, RANKL, and osteoprotegerin (OPG). However, the mechanisms of osteocyte mechanotransduction remain poorly understood. We've previously shown that osteocyte mechanosensitivity is encoded through unique intracellular calcium (Ca) dynamics.

Experimental studies of bone mechanoadaptation: bridging in vitro and in vivo studies with multiscale systems.

Despite advancements in technology and science over the last century, the mechanisms underlying Wolff's law-bone structure adaptation in response to physical stimuli-remain poorly understood, limiting the ability to effectively treat and prevent skeletal diseases. A challenge to overcome in the study of the underlying mechanisms of this principle is the multiscale nature of mechanoadaptation. While there exist in silico systems that are capable of studying across these scales, experimental studies are typically limited to interpretation at a single dimension or time point.