Mesenchymal stem cell extracellular vesicles-derived microRNA-194-5p delays the development of intervertebral disc degeneration by targeting TRAF6

Sun, Zhongyi; Tang, Xiaoming; Li, Qiuyuan; Wang, Haibin; Sun, Hongzhi; Tian, Jie

doi:10.1016/j.reth.2021.12.001

Cited by 17 publications

(14 citation statements)

References 41 publications

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“…Evidence was previously demonstrated suggesting that BMSC-Exos-derived miRNA delays the development of the intervertebral disc degeneration by targeting TRAF6 [ 44 ]. Another prior study indicated that miR-146a-5p overexpression inhibited the IRAK1/TRAF6/NF-κB pathway in acute pancreatitis [ 45 ].…”

Section: Resultsmentioning

confidence: 99%

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

Zhou

Zhang

et al. 2023

Nanomaterials

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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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Section: Resultsmentioning

confidence: 99%

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

Zhou

Zhang

et al. 2023

Nanomaterials

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“…As one of IDD's most promising and appealing regenerative strategies, stem cell‐based therapy has achieved great advances in treating different areas of degenerated diseases and IDD. 21 , 22 In IDD research, other kinds of stem cells also have been studied, including BMSCs, and ADMSCs. 23 , 24 The results of this research were promising.…”

Section: Discussionmentioning

confidence: 99%

Fisetin regulates the biological effects of rat nucleus pulposus mesenchymal stem cells under oxidative stress by sirtuin‐1 pathway

Zhou

Chen

Xuan

et al. 2023

Immunity Inflam & Disease

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Background Excessive oxidative stress has been accepted as one of the critical factors for intervertebral disc degeneration (IDD), which is associated with low back pain (LBP). Fisetin (Fis) is a bioactive flavonoid that possesses strong bioactive activity. In present study, we aimed to illuminate the role of Fis on nucleus pulposus mesenchymal stem cells (NPMSCs). Methods NPMSCs were isolated and cultured from rat NP tissues and identified by flow cytometry and multilinear differentiation. The cytotoxicity of Fis, EX‐527, and hydrogen peroxide (H2O2) on NPMSCs was validated using Cell Counting Kit‐8 tests. Cell apoptosis was tested by flow cytometry and TUNEL assay. Inflammatory mediators were assessed by Elisa tests, RT‐PCR. Extracellular matrix (ECM) metabolism was measured by Western blot analysis and RT‐qPCR. The expression of the SIRT1 was evaluated by Western blot analysis. Results NPMSCs were successfully isolated and cultured from rat NP tissues, and it has been identified by flow cytometry and multilinear differentiation. The results showed that Fis attenuated H2O2‐induced apoptosis, inflammation, and ECM degradation of NPMSCs. Moreover, the above protective effects of Fis can be inhibited by EX‐527, a unique SIRT1 inhibitor, indicating that SIRT1 may involve in the mechanism of Fis in protecting NPMSCs from oxidative stress. Conclusions As a natural compound with little cytotoxicity on NPMSCs, Fis alleviate H2O2‐induced apoptosis, inflammation, and ECM degradation by suppressing oxidative stress, this finding may add the theoretical basis for research on new treatment of IDD based on NPMSCs.

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“…MiR-21 in MSC-EVs inhibits NPCS apoptosis by targeting phosphatase and tensin homolog (PTEN) through the phosphatidylinositol 3-kinase (PI3K)-AKT pathway, a phenomenon not observed in fibroblast-EVs; this indicates that EVs derived from different mother cells have different functions. Bone marrow MSC-EVs Frontiers in Bioengineering and Biotechnology frontiersin.org deliver miRNAs through different pathways to inhibit NPC apoptosis (Table 1) (Zhu et al, 2020a;Zhu et al, 2020b;Cui and Zhang, 2021;Wen et al, 2021;Yu et al, 2022a;Yu et al, 2022b;Sun et al, 2022). Another study showed that the pH in degenerated IVD decreased from the normal 7.0-7.2 range to 6.5-5.7.…”

Section: Bmscsmentioning

confidence: 99%

Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

Xia

Yang²,

Hou³

et al. 2022

Front. Bioeng. Biotechnol.

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Intervertebral disc degeneration (IVDD) is a main cause of lower back pain, leading to psychological and economic burdens to patients. Physical therapy only delays pain in patients but cannot eliminate the cause of IVDD. Surgery is required when the patient cannot tolerate pain or has severe neurological symptoms. Although surgical resection of IVD or decompression of the laminae eliminates the diseased segment, it damages adjacent normal IVD. There is also a risk of re-protrusion after IVD removal. Cell therapy has played a crucial role in the development of regenerative medicine. Cell transplantation promotes regeneration of degenerative tissue. However, owing to the lack of vascular structure in IVD, sufficient nutrients cannot be provided for transplanted mesenchymal stem cells (MSCs). In addition, dead cells release harmful substances that aggravate IVDD. Extracellular vesicles (EVs) have been extensively studied as an emerging therapeutic approach. EVs generated by paracrine MSCs retain the potential of MSCs and serve as carriers to deliver their contents to target cells to regulate target cell activity. Owing to their double-layered membrane structure, EVs have a low immunogenicity and no immune rejection. Therefore, EVs are considered an emerging therapeutic modality in IVDD. However, they are limited by mass production and low loading rates. In this review, the structure of IVD and advantages of EVs are introduced, and the application of MSC-EVs in IVDD is discussed. The current limitations of EVs and future applications are described.

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Mesenchymal stem cell extracellular vesicles-derived microRNA-194-5p delays the development of intervertebral disc degeneration by targeting TRAF6

Cited by 17 publications

References 41 publications

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

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

Fisetin regulates the biological effects of rat nucleus pulposus mesenchymal stem cells under oxidative stress by sirtuin‐1 pathway

Application of mesenchymal stem cell-derived exosomes from different sources in intervertebral disc degeneration

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