Functional and analytical recapitulation of osteoclast biology on demineralized bone paper.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
07 Dec 2023
07 Dec 2023
Historique:
received:
24
04
2023
accepted:
27
11
2023
medline:
17
12
2023
pubmed:
8
12
2023
entrez:
7
12
2023
Statut:
epublish
Résumé
Osteoclasts are the primary target for osteoporosis drug development. Recent animal studies revealed the crucial roles of osteoblasts in regulating osteoclastogenesis and the longer lifespans of osteoclasts than previously thought with fission and recycling. However, existing culture platforms are limited to replicating these newly identified cellular processes. We report a demineralized bone paper (DBP)-based osteoblast culture and osteoclast assay platform that replicates osteoclast fusion, fission, resorption, and apoptosis with high fidelity and analytical power. An osteoid-inspired DBP supports rapid and structural mineral deposition by osteoblasts. Coculture osteoblasts and bone marrow monocytes under biochemical stimulation recapitulate osteoclast differentiation and function. The DBP-based bone model allows longitudinal quantitative fluorescent monitoring of osteoclast responses to bisphosphonate drug, substantiating significantly reducing their number and lifespan. Finally, we demonstrate the feasibility of humanizing the bone model. The DBP-based osteo assay platforms are expected to advance bone remodeling-targeting drug development with improved prediction of clinical outcomes.
Identifiants
pubmed: 38062034
doi: 10.1038/s41467-023-44000-9
pii: 10.1038/s41467-023-44000-9
pmc: PMC10703810
doi:
Substances chimiques
RANK Ligand
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8092Subventions
Organisme : NCI NIH HHS
ID : R00 CA163671
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA237171
Pays : United States
Organisme : NIAMS NIH HHS
ID : R21 AR079633
Pays : United States
Informations de copyright
© 2023. The Author(s).
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