Autophagy‐activated nucleus pulposus cells deliver exosomal miR‐27a to prevent extracellular matrix degradation by targeting MMP‐13

Zhang, Qichen; Hu, Shun-Qi; Hu, Annan; Zhang, Tai-Wei; Jiang, Libo; Li, Xilei

doi:10.1002/jor.24880

Cited by 31 publications

(27 citation statements)

References 44 publications

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“…The expression of miR-27a was detected by qRT-PCR for identification of successful transfection ( Figure 5A ). It has been reported that MMP-13 was a direct target of miR-27a ( Zhang et al, 2020 ). MiR-27a-mimics transfection effectively decreased the expression of GAS5 ( Figure 5B ) and MMP-13 ( Figures 5C–E , G-H ) and increased the expression of Col2a1 ( Figures 5D,F ).…”

Section: Resultsmentioning

confidence: 99%

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Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

et al. 2021

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Osteoarthritis (OA) is histopathologically marked by extracellular matrix (ECM) degradation in joint cartilage. Abnormal mechanical stimulation on joint cartilage may result in ECM degeneration and OA development. Matrix metalloproteinase 13 (MMP-13) is one of the catabolic enzymes contributing to the degradation of ECM, and it has become the potential biomarker for the therapeutic management of OA. Xanthohumol (XH), a naturally occurring prenylflavonoid derived from hops and beer, shows the protective activity against OA development. However, the potential mechanisms still need great effort. In this article, mechanical stimulation could significantly increase the expression of MMP-13 and lncRNA GAS5 (GAS5) and promoting ECM degradation. These could be effectively reversed by XH administration. Suppressed expression GAS5 ameliorated mechanical stimulation-induced MMP-13 expression. MiR-27a was predicted and verified as a target of GAS5, and overexpression of miR-27a down regulated the expression of MMP-13. Collectively, XH exhibited protective effects against mechanical stimulation-induced ECM degradation by mediating the GAS5/miR-27a signaling pathway in OA chondrocytes.

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Section: Resultsmentioning

confidence: 99%

“…In our study, miR-27a expression was significantly decreased in mechanical stimulation-treated chondrocytes. MMP-13 was a direct target of miR-27a ( Zhang et al, 2020 ), and miR-27a was a direct target of GAS5. Overexpression of miR-27a greatly decreased the expression of MMP-13 and GAS5 and increased the expression of Col2a1.…”

Section: Discussionmentioning

confidence: 99%

Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

et al. 2021

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“…In addition, miR-199a decreased MMP-2, MMP-6, TIMP-1 and apoptotic cells in a mouse model of IDD, while the expression of collagen type II, aggrecan, increased following the exposition to BMSC EVs in vitro [134]. Among other miRNAs previously identified, miR-27a was involved in the regulation of apoptotic pathways and in the prevention of IDD through the ability to suppress ECM degradation targeting MMP-13 [135,136]. Similarly, under TNF-α stimulation, exosomes extracted from BM-MSCs were able to secrete miR-532-5p.…”

Section: The Role Of Mirnas In Iddmentioning

confidence: 92%

Mesenchymal Stem Cell-Derived Exosomes: The New Frontier for the Treatment of Intervertebral Disc Degeneration

et al. 2021

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Low back pain (LBP) is one of the most frequent symptoms associated with intervertebral disc degeneration (IDD) and affects more than 80% of the population, with strong psychosocial and economic impacts. The main cause of IDD is a reduction in the proteoglycan content within the nucleus pulposus (NP), eventually leading to the loss of disc hydration, microarchitecture, biochemical and mechanical properties. The use of mesenchymal stem cells (MSCs) has recently arisen as a promising therapy for IDD. According to numerous reports, MSCs mediate their regenerative and immunomodulatory effects mainly through paracrine mechanisms. Recent studies have suggested that extracellular vesicles (EVs) extracted from MSCs may be a promising alternative to cell therapy in regenerative medicine. EVs, including exosomes and microvesicles, are secreted by almost all cell types and have a fundamental role in intercellular communication. Early results have demonstrated the therapeutic potential of MSCs-derived EVs for the treatment of IDD through the promotion of tissue regeneration, cell proliferation, reduction in apoptosis and modulation of the inflammatory response. The aim of this review is to focus on the biological properties, function, and regulatory properties of different signaling pathways of MSCs-derived exosomes, highlighting their potential applicability as an alternative cell-free therapy for IDD.

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“…The exosome-depleted FBS was obtained by ultracentrifugation, as described below. The medium was collected after 36 h of 10 ng/mL TNF-α pretreatment, followed by gradient centrifugation to remove debris, and ultracentrifugation at 120,000 ×g for 120 min, as previously described (17). The pellet was resuspended in PBS, quantified by bicinchoninic acid (BCA) protein assay (Beyotime, China), and cryopreserved at −80 ℃.…”

Section: Exosome Isolation and Identificationmentioning

confidence: 99%

“…Many studies have reported the protective role played by exosomal miRNAs that are derived from the cells involved in disc degeneration diseases, such as IDH (13)(14)(15)(16). Recently, we reported that the exosomal miR-27a derived from autophagyactivated healthy NPCs could repress IL-1β-induced NP matrix degradation by targeting matrix metalloprotease 13 (MMP-13) (17).…”

Section: Introductionmentioning

confidence: 99%

TNF-α-stimulated nucleus pulposus cells induce cell apoptosis through the release of exosomal miR-16 targeting IGF-1 and IGF-1R in rats

Zhang¹,

Zou²,

Hu³

et al. 2021

Ann Transl Med

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Background: Exosomes may contain excess cellular components released by cells in response to harmful external stimuli to maintain cellular homeostasis. Inflammatory cytokines, such as tumor necrosis factoralpha (TNF-α), can induce cell apoptosis, alter cellular component expression levels, and stimulate exosome release. In this study, we examined whether exosomes released from nucleus pulposus cells (NPCs) under inflammatory conditions could induce normal NP cell apoptosis in rats and its underlining mechanism.Methods: Exosomes were isolated from TNF-α-treated NPCs and used to treat normal NPCs. The effects were assessed by flow cytometry and western blot analysis. Anti-apoptotic insulin-like growth factor-1 (IGF-1) expression in NPCs was assessed by western blot analysis. Given the exosomal miRNAs might be the key factors of exosomes, bioinformatics approaches and quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify IGF-1-regulating micro RNAs (miRNAs), including miR-16. Luciferase reporter assay assessed miR-16 regulation of IGF-1 and IGF-1 receptor (IGF-1R). NPCs were transfected with miR-16 mimic, and exosomes were applied to normal NPCs. NPCs were pretreated with 10 ng/mL TNF-α, transfected with miR-16 inhibitors, and the exosomes were isolated. Cell and exosome miR-16 levels were detected by qRT-PCR. Western blot analysis determined IGF-1, IGF-1R, and apoptotic marker levels in exosome-treated NPCs.Results: Exosomes from TNF-α-treated NPCs induced apoptosis in normal NPCs and repressed IGF-1 expression. Exosomal miR-16 regulated IGF-1 and induced NPC apoptosis. The dual-luciferase reporter assay revealed that miR-16 binds the 3' untranslated regions (3'-UTRs) of IGF-1 and IGF-1R. Exosomal miR-16 repressed IGF-1 and the IGF-1R/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway which therefore induced NPC apoptosis. Rescue experiments using miR-16 inhibitors further validated these findings. Conclusions:The inflammatory factor TNF-α stimulated exosome release from NPCs, which induced the apoptosis of normal NPCs through the actions of exosomal miR-16. Exosomal miR-16 directly repressed the anti-apoptotic IGF-1/IGF-1R pathway, increasing the apoptosis of NPCs.

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Autophagy‐activated nucleus pulposus cells deliver exosomal miR‐27a to prevent extracellular matrix degradation by targeting MMP‐13

Cited by 31 publications

References 44 publications

Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

Mesenchymal Stem Cell-Derived Exosomes: The New Frontier for the Treatment of Intervertebral Disc Degeneration

TNF-α-stimulated nucleus pulposus cells induce cell apoptosis through the release of exosomal miR-16 targeting IGF-1 and IGF-1R in rats

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