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Cited by 26Bone Tissue Engineering MaterialsExtracellular vesicles in diseasePeriodontal Regeneration and Treatments

PF127 Hydrogel-Based Delivery of Exosomal CTNNB1 from Mesenchymal Stem Cells Induces Osteogenic Differentiation during the Repair of Alveolar Bone Defects

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He, Longlong, Zhou, Qin, Zhang, Hengwei, Zhao, Ningbo, Liao, Lifan·2023·Nanomaterials
DOI 10.3390/nano13061083PMC PMC10058633
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Abstract

Pluronic F127 (PF127) hydrogel has been highlighted as a promising biomaterial for bone regeneration, but the specific molecular mechanism remains largely unknown. Herein, we addressed this issue in a temperature-responsive PF127 hydrogel loaded with bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (Exos) (PF127 hydrogel@BMSC-Exos) during alveolar bone regeneration. Genes enriched in BMSC-Exos and upregulated during the osteogenic differentiation of BMSCs and their downstream regulators were predicted by bioinformatics analyses. CTNNB1 was predicted to be the key gene of BMSC-Exos in the osteogenic differentiation of BMSCs, during which miR-146a-5p, IRAK1, and TRAF6 might be the downstream factors. Osteogenic differentiation was induced in BMSCs, in which ectopic expression of CTNNB1 was introduced and from which Exos were isolated. The CTNNB1-enriched PF127 hydrogel@BMSC-Exos were constructed and implanted into in vivo rat models of alveolar bone defects. In vitro experiment data showed that PF127 hydrogel@BMSC-Exos efficiently delivered CTNNB1 to BMSCs, which subsequently promoted the osteogenic differentiation of BMSCs, as evidenced by enhanced ALP staining intensity and activity, extracellular matrix mineralization (p < 0.05), and upregulated RUNX2 and OCN expression (p < 0.05). Functional experiments were conducted to examine the relationships among CTNNB1, microRNA (miR)-146a-5p, and IRAK1 and TRAF6. Mechanistically, CTNNB1 activated miR-146a-5p transcription to downregulate IRAK1 and TRAF6 (p < 0.05), which induced the osteogenic differentiation of BMSCs and facilitated alveolar bone regeneration in rats (increased new bone formation and elevated BV/TV ratio and BMD, all with p < 0.05). Collectively, CTNNB1-containing PF127 hydrogel@BMSC-Exos promote the osteogenic differentiation of BMSCs by regulating the miR-146a-5p/IRAK1/TRAF6 axis, thus inducing the repair of alveolar bone defects in rats.

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  • The literature on genetically modified MSCs and MSCs on synthetic scaffolds has shown positive results in promoting osteogenic differentiation of MSCs and bone regrowth in both animal and human studies.

    “The literature surrounding the use of genetically modified MSCs as well as MSCs on synthetic scaffolds has shown positive results in terms of promoting osteogenic differentiation of MSCs and bone regrowth in both animal and human studies [87,88].”

    From Mesenchymal Stem/Stromal Cells: Immunomodulatory and Bone Regeneration Potential after Tumor Excision in Osteosarcoma Patients (2023) · cites this paper as [87]

    Section 3.7 reports increased osteogenic differentiation and alveolar bone formation using a PF127 hydrogel carrying exosomes from CTNNB1-overexpressing MSCs in rats. Section 3.3 also reports scaffold-loaded MSCs aiding bone repair in rhesus monkeys. These passages support positive animal results, but not bone regrowth in human studies; the paper’s own treatment delivers MSC-derived exosomes rather than scaffold-seeded MSCs. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
He, L., Zhou, Q., Zhang, H., Zhao, N., & Liao, L.
Affiliations
Xi'an Jiaotong University (CN)
Corresponding author
Liao, Lifan
ORCID
Venue
Nanomaterials
Publisher
MDPI AG
Published
2023-03-16
Volume
13
Issue
6
Pages
1083
ISSN
2079-4991 (ISSN-L)
DOI
10.3390/nano13061083
PMC
PMC10058633
OpenAlex
W4327716452
Cited by
26
References
2
Citations by year
2026: 6 · 2025: 8 · 2024: 9 · 2023: 3
FWCI
2.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Nanomaterials (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Science and Technology Bureau of Xi’an of China (21YXYJ0124, 2022JH-YBYJ-0354, 22078209)
  • National Natural Science Foundation of China (21YXYJ0124, 2022JH-YBYJ-0354, 22078209)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Health Sciences › Medicine › Urology › Periodontal Regeneration and Treatments
Keywords
exosomes, mesenchymal stem cells, CTNNB1, osteogenic differentiation, alveolar bone regeneration, bone marrow mesenchymal stem cells, miR-146a, IRAK1, TRAF6, Wnt/β-catenin signaling, bone regeneration biomaterials, Runx2

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