Nanoscale zeolitic imidazolate framework-8 activator of canonical MAPK signaling for bone repair
Abstract
Zeolitic imidazolate framework-8 (ZIF-8) is an important type of metal organic framework and has found numerous applications in the biomedical field. Our previous studies have demonstrated that nano ZIF-8-based titanium implants could promote osseointegration; however, its osteogenic capacity and the related mechanisms in bone regeneration have not been fully clarified. Presented here is a nanoscale ZIF-8 that could drive rat bone mesenchymal stem cell (rBMSC) differentiation into osteoblasts both in vitro and in vivo, and interestingly, nano ZIF-8 exhibited a better osteogenic effect compared with ionic conditions of Zn at the same concentration of Zn 2+ . Moreover, the cellular uptake mechanisms of the nanoparticles were thoroughly clarified. Specifically, nano ZIF-8 could enter the rBMSC cytoplasm probably via caveolae-mediated endocytosis and macropinocytosis. The intracellular and extracellular Zn 2+ released from nano ZIF-8 and the receptors involved in the endocytosis may play a role in inducing activation of key osteogenic pathways. Furthermore, through transcriptome sequencing, multiple osteogenic pathways were found to be upregulated, among which nano ZIF-8 primarily phosphorylated ERK, thus activating the canonical mitogen-activated protein kinase pathway and promoting the osteogenesis of rBMSCs. Taken together, this study helps to elucidate the mechanism by which nano ZIF-8 regulates osteogenesis and suggests it to be a potential biomaterial for constructing multifunctional composites in bone tissue engineering.
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BMSCs internalize ZIF-8 nanoparticles via caveolin-mediated endocytosis and phagocytosis.
“Existing studies reveal that BMSCs internalize ZIF-8 nanoparticles via caveolin-mediated endocytosis and phagocytosis [51].”
From Hydrogel scaffold encapsulating MSC-Exos and ZIF-8 promotes bone regeneration via coordinating osteogenesis and immunomodulation (2025) · cites this paper as [51]
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- Authors
- Gao, X., Xue, Y., Zhu, Z., Chen, J., Liu, Y., Cheng, X., Zhang, X., Wang, J., Pei, X., & Wan, Q.
- Affiliations
- Sichuan University (CN)
- Corresponding author
- Pei, Xibo
- Wan, Qianbing
- ORCID
- Venue
- ACS Applied Materials & Interfaces
- Publisher
- American Chemical Society (ACS)
- Published
- 2020-12-23
- Volume
- 13
- Issue
- 1
- Pages
- 97-111
- ISSN
- 1944-8244 (ISSN-L)
- 1944-8252
- OpenAlex
- W3145906564
- Cited by
- 127
- References
- 64
- Citations by year
- 2026: 13 · 2025: 33 · 2024: 19 · 2023: 30 · 2022: 27 · 2021: 5
- FWCI
- 4.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- ACS Applied Materials & Interfaces (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Science and Technology of Sichuan Province (21ZDYF1797)
- National Natural Science Foundation of China (81771122, 81970984, 81970985, 82071164)
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
- Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Organic Frameworks: Synthesis and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Keywords
- ZIF-8, metal-organic frameworks, nanomaterials, bone regeneration, osteogenic differentiation, bone mesenchymal stem cells, ERK1/2 phosphorylation, MAPK signaling, zinc ion release, caveolae-mediated endocytosis, macropinocytosis, cellular uptake, osseointegration, bone tissue engineering
- MeSH terms
- Metal-Organic Frameworks, Alginates, Animals, Bone and Bones, Bone Regeneration, Cell Differentiation, Drug Carriers, Endocytosis, Male, Osteoblasts, Osteogenesis, Pinocytosis, Zinc, Rats, Sprague-Dawley, Hydrogels, MAP Kinase Signaling System, Cell Proliferation, Rats, Nanoparticles, Mesenchymal Stem Cells
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