Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived Macrophages
Chenyi Zhang,1,* Lai Pan,1,* Haizheng Zhang,1 Ting Ke,1 Yuxuan Yang,1 Lan Zhang,2 Lili Chen,1 Jingyi Tan1 1Department of Periodontology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 2Stomatology Department, Zhejiang...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2023-02-01
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| Series: | International Journal of Nanomedicine |
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| Online Access: | https://www.dovepress.com/osteoblasts-derived-exosomal-lncrna-malat1-promotes-osteoclastogenesis-peer-reviewed-fulltext-article-IJN |
| _version_ | 1811164164591190016 |
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| author | Zhang C Pan L Zhang H Ke T Yang Y Zhang L Chen L Tan J |
| author_facet | Zhang C Pan L Zhang H Ke T Yang Y Zhang L Chen L Tan J |
| author_sort | Zhang C |
| collection | DOAJ |
| description | Chenyi Zhang,1,* Lai Pan,1,* Haizheng Zhang,1 Ting Ke,1 Yuxuan Yang,1 Lan Zhang,2 Lili Chen,1 Jingyi Tan1 1Department of Periodontology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 2Stomatology Department, Zhejiang Hospital, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lili Chen; Jingyi Tan, Email chenlili_1030@zju.edu.cn; tanjingyi@zju.edu.cnObjective: Emerging studies have explained the crucial role of non-coding RNA (lncRNA) in various pathological progressions. The study was designed to examine the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miRNA-124 in the differentiation of osteoclasts, to provide new clues or evidences for the pathogenesis of periodontitis.Methods: We constructed an osteoblast-osteoclast Transwell co-culture system and osteoblast-derived exosomes (OB-exo) intervention model. We assessed the osteoclastogenesis as well as the level of lncRNA-MALAT1 and miRNA-124. The mechanism for lncRNA MALAT1 targeting miR-124 modulating the differentiation of osteoclasts was investigated by cell transfection, quantitative real-time reverse transcription PCR (RT-qPCR), Western blot, and Dual-Luciferase reporter assays.Results: Osteoblast-derived exosomes were isolated and identified. Co-culture and OB-exo intervention can promote osteoclastogenesis, also significantly up-regulate the expression of MALAT1, while the level of miR-124 is the opposite. Transfection of cells with small interfering RNA (si-MALAT1) and miR-124 mimic decreased the formation of TRAP+ osteoclasts and inhibited the expression of NFATc1. However, the effect was reversed when transfected with miR-124 inhibitor and si-MALAT1. The Dual-Luciferase reporter assay confirmed the binding sites between MALAT1 and miR-124, and miR-124 and NFATc1.Conclusion: LncRNA MALAT1 functioned as an endogenous sponge by competing for miR-124 binding to regulate NFATc1 expression, accelerating the progression of osteoclastogenesis.Graphical Abstract: Keywords: exosome, lncRNA, miRNA-124, osteoclast differentiation |
| first_indexed | 2024-04-10T15:16:56Z |
| format | Article |
| id | doaj.art-2800644dbd004f9a828aa88715a59f53 |
| institution | Directory Open Access Journal |
| issn | 1178-2013 |
| language | English |
| last_indexed | 2024-04-10T15:16:56Z |
| publishDate | 2023-02-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-2800644dbd004f9a828aa88715a59f532023-02-14T18:00:38ZengDove Medical PressInternational Journal of Nanomedicine1178-20132023-02-01Volume 1878179581646Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived MacrophagesZhang CPan LZhang HKe TYang YZhang LChen LTan JChenyi Zhang,1,* Lai Pan,1,* Haizheng Zhang,1 Ting Ke,1 Yuxuan Yang,1 Lan Zhang,2 Lili Chen,1 Jingyi Tan1 1Department of Periodontology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, People’s Republic of China; 2Stomatology Department, Zhejiang Hospital, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lili Chen; Jingyi Tan, Email chenlili_1030@zju.edu.cn; tanjingyi@zju.edu.cnObjective: Emerging studies have explained the crucial role of non-coding RNA (lncRNA) in various pathological progressions. The study was designed to examine the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miRNA-124 in the differentiation of osteoclasts, to provide new clues or evidences for the pathogenesis of periodontitis.Methods: We constructed an osteoblast-osteoclast Transwell co-culture system and osteoblast-derived exosomes (OB-exo) intervention model. We assessed the osteoclastogenesis as well as the level of lncRNA-MALAT1 and miRNA-124. The mechanism for lncRNA MALAT1 targeting miR-124 modulating the differentiation of osteoclasts was investigated by cell transfection, quantitative real-time reverse transcription PCR (RT-qPCR), Western blot, and Dual-Luciferase reporter assays.Results: Osteoblast-derived exosomes were isolated and identified. Co-culture and OB-exo intervention can promote osteoclastogenesis, also significantly up-regulate the expression of MALAT1, while the level of miR-124 is the opposite. Transfection of cells with small interfering RNA (si-MALAT1) and miR-124 mimic decreased the formation of TRAP+ osteoclasts and inhibited the expression of NFATc1. However, the effect was reversed when transfected with miR-124 inhibitor and si-MALAT1. The Dual-Luciferase reporter assay confirmed the binding sites between MALAT1 and miR-124, and miR-124 and NFATc1.Conclusion: LncRNA MALAT1 functioned as an endogenous sponge by competing for miR-124 binding to regulate NFATc1 expression, accelerating the progression of osteoclastogenesis.Graphical Abstract: Keywords: exosome, lncRNA, miRNA-124, osteoclast differentiationhttps://www.dovepress.com/osteoblasts-derived-exosomal-lncrna-malat1-promotes-osteoclastogenesis-peer-reviewed-fulltext-article-IJNexosomelncrnamirna-124osteoclast differentiation |
| spellingShingle | Zhang C Pan L Zhang H Ke T Yang Y Zhang L Chen L Tan J Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived Macrophages International Journal of Nanomedicine exosome lncrna mirna-124 osteoclast differentiation |
| title | Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived Macrophages |
| title_full | Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived Macrophages |
| title_fullStr | Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived Macrophages |
| title_full_unstemmed | Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived Macrophages |
| title_short | Osteoblasts-Derived Exosomal lncRNA-MALAT1 Promotes Osteoclastogenesis by Targeting the miR-124/NFATc1 Signaling Axis in Bone Marrow-Derived Macrophages |
| title_sort | osteoblasts derived exosomal lncrna malat1 promotes osteoclastogenesis by targeting the mir 124 nfatc1 signaling axis in bone marrow derived macrophages |
| topic | exosome lncrna mirna-124 osteoclast differentiation |
| url | https://www.dovepress.com/osteoblasts-derived-exosomal-lncrna-malat1-promotes-osteoclastogenesis-peer-reviewed-fulltext-article-IJN |
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