破骨细胞
成骨细胞
骨重建
骨吸收
细胞生物学
双膦酸盐
骨髓
类骨质
骨质疏松症
骨不连
生物
免疫学
内分泌学
体外
解剖
生物化学
作者
Yongkuk Park,Tadatoshi Sato,Jungwoo Lee
标识
DOI:10.1038/s41467-023-44000-9
摘要
Abstract 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.
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