Fenoldopam Sensitizes Primary Cilia-Mediated Mechanosensing to Promote Osteogenic Intercellular Signaling and Whole Bone Adaptation.

ABSTRACT: Bone cells actively respond to mechanical stimuli to direct bone formation, yet there is no current treatment strategy for conditions of low bone mass and osteoporosis designed to target the inherent mechanosensitivity of bone. Our group has previously identified the primary cilium as a critical mechanosensor within bone, and that pharmacologically targeting the primary cilium with fenoldopam can enhance osteocyte mechanosensitivity. Here, we demonstrate that potentiating osteocyte mechanosensing with fenoldopam in vitro promotes pro-osteogenic paracrine signaling to osteoblasts. Conversely, impairing primary cilia formation and the function of key ciliary mechanotransduction proteins attenuates this intercellular signaling cascade. We then utilize an in vivo model of load-induced bone for

SUBMITTER: Spasic M 

PROVIDER: S-EPMC9098671 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature