Abstract
AbstractOsteoclasts 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.
Funder
U.S. Department of Health & Human Services | NIH | National Cancer Institute
National Science Foundation
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference70 articles.
1. Wright, N. C. et al. The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J. Bone Min. Res. 29, 2520–2526 (2014).
2. Sarafrazi, N., Wambogo, E. A., Shepherd, J. A. Osteoporosis or low bone mass in older adults: United States, 2017-2018. NCHS Data Brief, 405, 1–8 (2021).
3. Johnell, O. et al. Mortality after osteoporotic fractures. Osteoporos. Int. 15, 38–42 (2004).
4. Food and Drug Administration. Drug Safety Communication: safety update for osteoporosis drugs, bisphosphonates, and atypical fractures, October 13, 2010 (Food and Drug Administration, 2017).
5. Black, D. M. et al. Effects of continuing or stopping alendronate after 5 years of treatment: the Fracture Intervention Trial Long-term Extension (FLEX): a randomized trial. JAMA 296, 2927–2938 (2006).