Dataset Information

MSC-Derived Exosomes Protect Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the miR-31-5p/ATF6 Axis.

ABSTRACT: Apoptosis and calcification of endplate chondrocytes (EPCs) can exacerbate intervertebral disc degeneration (IVDD). Mesenchymal stem cell-derived exosomes (MSC-exosomes) are reported to have the therapeutic potential in IVDD. However, the effects and related mechanisms of MSC-exosomes on EPCs are still unclear. We aimed to investigate the role of MSC-exosomes on EPCs with a tert-butyl hydroperoxide (TBHP)-induced oxidative stress cell model and IVDD rat model. First, our study revealed that TBHP could result in apoptosis and calcification of EPCs, and MSC-exosomes could inhibit the detrimental effects. We also found that these protective effects were inhibited after miroRNA (miR)-31-5p levels were downregulated in MSC-exosomes. The target relationship between miR-31-5p and ATF6 was tested. miR-31-5p negatively regulated ATF6-related endoplasmic reticulum (ER) stress and inhibited apoptosis and calcification in EPCs. Our in vivo experiments indicated that sub-endplate injection of MSC-exosomes can ameliorate IVDD; however, after miR-31-5p levels were downregulated in MSC-exosomes, these protective effects were inhibited. In conclusion, MSC-exosomes reduced apoptosis and calcification in EPCs, and the underlying mechanism may be related to miR-31-5p/ATF6/ER stress pathway regulation.

SUBMITTER: Xie L

PROVIDER: S-EPMC7569190 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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MSC-Derived Exosomes Protect Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the miR-31-5p/ATF6 Axis.

Xie Lin L Chen Zhenhao Z Liu Ming M Huang Weibo W Zou Fei F Ma Xiaosheng X Tao Jie J Guo Jingkang J Xia Xinlei X Lyu Feizhou F Wang Hongli H Zheng Chaojun C Jiang Jianyuan J

Molecular therapy. Nucleic acids 20200926

Apoptosis and calcification of endplate chondrocytes (EPCs) can exacerbate intervertebral disc degeneration (IVDD). Mesenchymal stem cell-derived exosomes (MSC-exosomes) are reported to have the therapeutic potential in IVDD. However, the effects and related mechanisms of MSC-exosomes on EPCs are still unclear. We aimed to investigate the role of MSC-exosomes on EPCs with a tert-butyl hydroperoxide (TBHP)-induced oxidative stress cell model and IVDD rat model. First, our study revealed that TBHP ...[more]

PMID: 33230460

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Project description:BackgroundAlthough deformation and fracture of the vertebral endplate have been implicated in spinal conditions such as vertebral fracture and disc degeneration, few biomechanical studies of this structure are available. The goal of this study was to quantify the mechanical behavior of the vertebral endplate.MethodsEight-five rectangular specimens were dissected from the superior and/or inferior central endplates of human lumbar spine segments L1 to L4. Micro-computed tomography (μCT) imaging, four-point-bend testing, and ashing were performed to quantify the apparent elastic modulus and yield stress (modulus and yield stress, respectively, of the porous vertebral endplate), tissue yield stress (yield stress of the tissue of the vertebral endplate, excluding pores), ultimate strain, fracture strain, bone volume fraction (BV/TV), bone mineral density (BMD), and various measures of tissue density and composition (tissue mineral density, ash fraction, and ash density). Regression was used to assess the dependence of mechanical properties on density and composition.ResultsWide variations in elastic and failure properties, and in density and tissue composition, were observed. BMD and BV/TV were good predictors of many of the apparent-level mechanical properties, including modulus, yield stress, and in the case of the inferior vertebral endplate, failure strains. Similar values of the mechanical properties were noted between superior and inferior vertebral endplates. In contrast to the dependence of apparent stiffness and strength on BMD and BV/TV, none of the mechanical properties depended on any of the tissue-level density measurements.ConclusionThe dependence of many of the mechanical properties of the vertebral endplate on BV/TV and BMD suggests possibilities for noninvasive assessment of how this region of the spine behaves during habitual and injurious loading. Further study of the nonmineral components of the endplate tissue is required to understand how the composition of this tissue may influence the overall mechanical behavior of the vertebral endplate.

Dataset Information

MSC-Derived Exosomes Protect Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the miR-31-5p/ATF6 Axis.

Publications

MSC-Derived Exosomes Protect Vertebral Endplate Chondrocytes against Apoptosis and Calcification via the miR-31-5p/ATF6 Axis.

Similar Datasets

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