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Cited by 84Bone Metabolism and DiseasesBone Tissue Engineering MaterialsBone health and osteoporosis research

Bone-targeted pH-responsive cerium nanoparticles for anabolic therapy in osteoporosis

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Dou, Ce, Li, Jianmei, He, Jian, Luo, Fei, Yu, Tao, Dai, Qijie, Chen, Yueqi, Xu, Jianzhong +2 more·2021·Bioactive Materials
DOI 10.1016/j.bioactmat.2021.04.038PMC PMC8164008
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Abstract

Antiresorptive drugs are widely used for treatment of osteoporosis and cancer bone metastasis, which function mainly through an overall inhibition of osteoclast. However, not all osteoclasts are "bone eaters"; preosteoclasts (pOCs) play anabolic roles in bone formation and angiogenesis through coupling with osteoblasts and secreting platelet derived growth factor-BB (PDGF-BB). In this study, a bone-targeted pH-responsive nanomaterial was designed for selectively eliminating mature osteoclasts (mOCs) without affecting pOCs. Biocompatible cerium nano-system (CNS) was guided to the acidic extracellular microenvironment created by mOCs and gained oxidative enzymatic activity. Oxidative CNS decreased the viability of mOCs through accumulating intracellular reactive oxygen species and enhancing calcium oscillation. Non-acid secreting anabolic pOCs were thus preserved and kept producing PDGF-BB, which lead to mesenchymal stem cell osteogenesis and endothelial progenitor cell angiogenesis via PI3K-Akt activated focal adhesion kinase. In treating osteoporotic ovariectomized mice, CNS showed better protective effects compare with the current first line antiresorptive drug due to the better anabolic effects marked by higher level of bone formation and vascularization. We provided a novel anabolic therapeutic strategy in treating bone disorders with excessive bone resorption.

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  • CeNPs promote angiogenesis and osteogenesis by alleviating oxidative stress and modulating osteocyte signaling via the TGF-β/BMP pathway.

    “Additionally, CeNPs promote angiogenesis and osteogenesis by alleviating oxidative stress and modulating osteocyte signaling via the TGF-β/BMP pathway22,23.”

    From Microenvironment-responsive multifunctional enzyme-linked hydrogel for diabetic bone defect regeneration. (2025) · cites this paper as [23]

    The Results section, “pOCs preserved by CNS induce osteogenesis and angiogenesis via FAK pathway,” reports increased MSC osteogenesis and endothelial progenitor cell tube formation with CNS treatment. It attributes these effects to preserved preosteoclasts, PDGF-BB and PI3K–Akt–FAK signaling, not osteocyte signaling through TGF-β/BMP. The Conclusions also state that CNS increased ROS accumulation in mature osteoclasts, so the proposed mechanism of alleviating oxidative stress is not supported. (LLM, conf=0.90)

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Cited by

Sorted by citations

Authors
Dou, C., Li, J., He, J., Luo, F., Yu, T., Dai, Q., Chen, Y., Xu, J., Yang, X., & Dong, S.
Affiliations
Army Medical University (CN)
Corresponding author
  • Xu, Jianzhong
  • Yang, Xiaochao
  • Dong, Shiwu
ORCID
Venue
Bioactive Materials
Publisher
Elsevier BV
Published
2021-12
Volume
6
Issue
12
Pages
4697-4706
ISSN
  • 2097-1192 (ISSN-L)
  • 2452-199X
DOI
10.1016/j.bioactmat.2021.04.038
PMC
PMC8164008
OpenAlex
W3164826157
Cited by
84
References
2
Citations by year
2026: 9 · 2025: 17 · 2024: 18 · 2023: 22 · 2022: 17 · 2021: 1
FWCI
4.55
Type
journal article
Language
en
Open access
Licence
Locations
  • Bioactive Materials (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81802166, 81930067)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords
cerium nanoparticles, pH-responsive nanomaterials, osteoporosis, osteoclasts, osteoclast precursors, bone-targeted drug delivery, reactive oxygen species, calcium oscillations, PDGF-BB, PI3K/Akt signaling, focal adhesion kinase, bone resorption, antiresorptive therapy, ovariectomized mice

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