Fenoldopam Sensitizes Primary Cilia-Mediated Mechanosensing to Promote Osteogenic Intercellular Signaling and Whole Bone Adaptation.
BONE HISTOMORPHOMETRY
FENOLDOPAM
MECHANOTRANSDUCTION
OSTEOPOROSIS
PRIMARY CILIA
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
revised:
01
02
2022
received:
28
06
2021
accepted:
12
02
2022
pubmed:
2
3
2022
medline:
18
5
2022
entrez:
1
3
2022
Statut:
ppublish
Résumé
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 formation to demonstrate that fenoldopam treatment sensitizes bones of both healthy and osteoporotic mice to mechanical stimulation. Furthermore, we show minimal adverse effects of this treatment and demonstrate that prolonged treatment biases trabecular bone adaptation. This work is the first to examine the efficacy of targeting primary cilia-mediated mechanosensing to enhance bone formation in osteoporotic animals. © 2022 American Society for Bone and Mineral Research (ASBMR).
Identifiants
pubmed: 35230705
doi: 10.1002/jbmr.4536
pmc: PMC9098671
mid: NIHMS1784992
doi:
Substances chimiques
Fenoldopam
INU8H2KAWG
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
972-982Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR062177
Pays : United States
Informations de copyright
© 2022 American Society for Bone and Mineral Research (ASBMR).
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