Adenylyl cyclases and TRPV4 mediate Ca²⁺/cAMP dynamics to enhance fluid flow-induced osteogenesis in osteocytes.

ABSTRACT: Bone adapts to physical forces and this process is dependent on osteocyte mechanotransduction. One way osteocytes sense mechanical stimulation is through the primary cilium, a sensory organelle that triggers intracellular signaling cascades in response to fluid shear. Our lab previously determined that flow-induced ciliary Ca²⁺ influx and changes in cytosolic cAMP levels are critical for osteogenesis. We also identified two proteins important for osteocyte mechanotransduction: transient receptor potential vanilloid 4 (TRPV4) and adenylyl cyclase 6 (AC6). Interestingly, disrupting the Ca²⁺-binding ability of these proteins results in loss of function. Although knockdowns of TRPV4 and AC6 disrupt osteogenesis, there is no definitive evidence linking them to Ca²⁺

SUBMITTER: Moore ER 

PROVIDER: S-EPMC6529196 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature