MicroRNA-130a regulates chondrocyte proliferation and alleviates osteoarthritis through PTEN/PI3K/Akt signaling pathway

Zhang, Yun; Xu, Shaochen; Huang, L. Eric; Zhou, Haichao; Li, Bing; Shao, Chenni; Yang, Yunfeng

doi:10.3892/ijmm.2018.3551

Cited by 10 publications

(11 citation statements)

References 23 publications

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“…To clarify the downstream mechanism of miR‐26a‐5p after its entry into SW1353 cells, the target genes of miR‐26a‐5p were predicted through a database and 49 genes were obtained in the intersection (Figure 5A). Among them, PTEN was reported to be high‐expressed in OA 25,26 . Based on the binding site between miR‐26a‐5p and PTEN, a dual‐luciferase reporter gene assay was performed (Figure 5B), which confirmed the target binding relationship between miR‐26a‐5p and PTEN ( p < 0.01) (Figure 5C).…”

Section: Resultsmentioning

confidence: 70%

Synovial mesenchymal stem cell‐derived extracellular vesicles containing microRN555A‐26a‐5p ameliorate cartilage damage of osteoarthritis

Wang

Fan

et al. 2021

The Journal of Gene Medicine

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Background Osteoarthritis (OA) is a degenerative disease characterized by cartilage damage. We aimed to improve the understanding of the protective mechanism of synovial mesenchymal stem cell (SMSC)‐derived extracellular vesicles (EVs) in cartilage damage of OA. Methods SMSCs and SMSC‐EVs were isolated from synovial biopsies of patients without OA and then identified. The pathological microenvironment of chondrocytes in OA was simulated by inducing SW1353 cells with interleukin (IL)‐1β, followed by SMSC‐EV treatment to assess SW1353 cell proliferation, apoptosis and inflammation. Endocytosis of Dil‐labeled EVs by SW1353 cells was observed. microRNA (miR)‐26a‐5p expression in EVs and EV‐treated SW1353 cells was assessed. The effect of miR‐26a‐5p was evaluated after it was down‐regulated in SMSCs, followed by extraction of EVs, which acted on SW1353 cells. The target relationship of miR‐26a‐5p and phosphatase and tensin homologue (PTEN) was predicted and confirmed. The role of PTEN in OA was evaluated after it was overexpressed. Functional assays were implemented in vivo to certify the role of SMSC‐EVs in OA. Results SMSC‐EVs enhanced IL‐1β‐induced SW1353 cell proliferation, whereas they inhibited apoptosis and inflammation. EVs were endocytosed by SW1353 cells and delivered miR‐26a‐5p into SW1353 cells to overexpress miR‐26a‐5p. Down‐regulation of miR‐26a‐5p in EVs attenuated the protection of EVs against IL‐1β‐induced cell damage. miR‐26a‐5p targeted PTEN, for which overexpression spoiled the protection of EVs against IL‐1β‐induced cell damage. SMSC‐EVs carrying miR‐26a‐5p repaired cartilage damage of OA. Conclusions SMSC‐EVs carried miR‐26a‐5p into chondrocytes to up‐regulate miR‐26a‐5p and inhibit PTEN, thereby inhibiting apoptosis and inflammation and ameliorating cartilage damage of OA.

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Section: Resultsmentioning

confidence: 70%

Synovial mesenchymal stem cell‐derived extracellular vesicles containing microRN555A‐26a‐5p ameliorate cartilage damage of osteoarthritis

Wang

Fan

et al. 2021

The Journal of Gene Medicine

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“…Zeng et al (2019) showed that high expression of MMP3 was observed in OA synovial cells, and curcumin could control cell proliferation and induce cell apoptosis by inhibiting MMP3 expression, eventually alleviating OA inflammation. AKT, a serine/threonine protein kinase, is an effector of the PI3K/AKT signaling pathway (Malemud, 2015) and is involved in multiple biological processes, including cell growth, apoptosis, migration, and metabolism (Zhang et al, 2018). PTEN is an important negative regulator of the PI3K/AKT signaling pathway, and loss of PTEN can lead to the activation of the PI3K/AKT signaling pathway (Xi et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…PTEN is an important negative regulator of the PI3K/AKT signaling pathway, and loss of PTEN can lead to the activation of the PI3K/AKT signaling pathway (Xi et al, 2020). A study by Zhang et al (2018) indicated that miRNA-130a could regulate cell growth and relieve OA via the PTEN/PI3K/AKT signaling pathway. Additionally, GRPR is a member of the G-protein coupled receptor superfamily and affects cell growth and invasion (Elshafae et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Exosomes Isolated From Bone Marrow Mesenchymal Stem Cells Exert a Protective Effect on Osteoarthritis via lncRNA LYRM4-AS1-GRPR-miR-6515-5p

Wang

Chen

et al. 2021

Front. Cell Dev. Biol.

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ObjectivesThe aim of this study was to investigate the effects of exosomes isolated from human bone marrow mesenchymal stem cells (BMSCs) on osteoarthritis (OA) and a competitive endogenous RNA (ceRNA) network.MethodsExosomes were isolated from human BMSCs and characterized by transmission electron microscopy (TEM), Nanosight (NTA), and western blotting. Chondrocytes were treated with interleukin-1β (IL-1β) and then transfected with exosomes. Cell viability and apoptosis were determined using Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. Cells with IL-1β and exosomes were sequenced, and differentially expressed lncRNAs (DE-lncRNAs) and miRNAs (DE-miRNAs) were identified. Thereafter, a ceRNA network (LYRM4-AS1-GRPR-miR-6515-5p) was chosen for further validation.ResultsTEM, NTA, and western blotting showed that exosomes were successfully isolated, and PKH67 staining showed that exosomes could be taken up by IL-1β-induced chondrocytes. Compared with the control group, IL-1β significantly decreased cell viability and promoted apoptosis (P < 0.05), while exosomes reversed the changes induced by IL-1β. For MMP3, AKT, and GRPR, IL-1β upregulated their expression, while exosomes downregulated their expression. For PTEN, there was no significant difference in PTEN expression between the control and IL-1β groups; however, exosomes markedly upregulated PTEN expression. By sequencing, 907 DE-lncRNAs and 25 DE-miRNAs were identified, and a ceRNA network was constructed. The dual-luciferase reporter gene indicated that LYRM4-AS1, miR-6515-5, and GRPR interacted with each other. The results of cell experiments showed that LYRM4-AS1 regulated the growth of IL-1β-induced chondrocytes by GRPR/miR-6515-5p.ConclusionExosomes may alleviate OA inflammation by regulating the LYRM4-AS1/GRPR/miR-6515-5p signaling pathway.

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“…There is increasing evidence that miRNAs are key endogenous regulators of stem cell differentiation [3, 6–9]. Use of miRNA mimics is an excellent strategy to enhance osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs), which contain 20–30 nucleotides, regulate endogenous gene expression by inhibiting posttranscriptional gene expression or inducing degradation of their targets via binding to the 3′ untranslated regions of messenger RNAs (mRNAs) [1–5]. Accumulated evidence suggests that many miRNAs help to regulate osteogenic differentiation of bone mesenchymal stem cells (BMSCs) [3, 6–9]. MiR-29b, one of the most widely investigated miRNAs, regulates osteogenic differentiation via several mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Delivery of miRNA-29b Using R9-LK15, a Novel Cell-Penetrating Peptide, Promotes Osteogenic Differentiation of Bone Mesenchymal Stem Cells

Liu

Lin

Liu

et al. 2019

BioMed Research International

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Delivery of osteogenesis-promoting microRNAs (miRNAs) is a promising approach to enhance bone regeneration. In this study, we generated nanocomplexes comprising the novel cell-penetrating peptide R9-LK15 and miR-29b and investigated their effects on osteogenic differentiation of bone mesenchymal stem cells (BMSCs). R9-LK15/miR-29b nanocomplexes were prepared and characterized. The transfection efficiency, cell viability, and osteogenic differentiation were investigated. The results showed that R9-LK15 maintained the stability of miR-29b in serum for up to 24 h. Moreover, R9-LK15 efficiently delivered miR-29b into BMSCs; the transfection efficiency was ~10-fold higher than that achieved using Lipofectamine 2000. The Cell Counting Kit-8 assay showed that R9-LK15 and R9-LK15/miR-29b nanocomplexes had negligible cytotoxic effects on BMSCs. Delivery of R9-LK15/miR-29b nanocomplexes promoted osteogenic differentiation of BMSCs and extracellular matrix mineralization by upregulating alkaline phosphatase expression and downregulating histone deacetylase-4 expression. In general, we developed a novel miRNA delivery system that has a high transfection efficiency and promotes osteogenic differentiation.

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MicroRNA-130a regulates chondrocyte proliferation and alleviates osteoarthritis through PTEN/PI3K/Akt signaling pathway

Cited by 10 publications

References 23 publications

Synovial mesenchymal stem cell‐derived extracellular vesicles containing microRN555A‐26a‐5p ameliorate cartilage damage of osteoarthritis

Synovial mesenchymal stem cell‐derived extracellular vesicles containing microRN555A‐26a‐5p ameliorate cartilage damage of osteoarthritis

Exosomes Isolated From Bone Marrow Mesenchymal Stem Cells Exert a Protective Effect on Osteoarthritis via lncRNA LYRM4-AS1-GRPR-miR-6515-5p

Delivery of miRNA-29b Using R9-LK15, a Novel Cell-Penetrating Peptide, Promotes Osteogenic Differentiation of Bone Mesenchymal Stem Cells

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