دورية أكاديمية
lncRNA Rmst acts as an important mediator of BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) by antagonizing Notch-targeting microRNAs.
| العنوان: | lncRNA Rmst acts as an important mediator of BMP9-induced osteogenic differentiation of mesenchymal stem cells (MSCs) by antagonizing Notch-targeting microRNAs. |
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| المؤلفون: | Zhang Z; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA., Liu J; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA., Zeng Z; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Fan J; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Huang S; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Zhang L; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Zhang B; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Key Laboratory of Orthopaedic Surgery of Gansu Province, and the Departments of Orthopaedic Surgery and Obstetrics and Gynecology, The First and Second Hospitals of Lanzhou University, Lanzhou 730030, China., Wang X; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Feng Y; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Ye Z; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China., Zhao L; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Cao D; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China.; Departments of Orthopaedic Surgery and Laboratory Medicine, Chongqing General Hospital, Chongqing 400013, China., Yang L; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Key Laboratory of Orthopaedic Surgery of Gansu Province, and the Departments of Orthopaedic Surgery and Obstetrics and Gynecology, The First and Second Hospitals of Lanzhou University, Lanzhou 730030, China., Pakvasa M; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA., Liu B; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; School of Life Sciences, Southwest University, Chongqing 400715, China., Wagstaff W; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA., Wu X; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Luo H; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Department of Burn and Plastic Surgery, West China Hospital of Sichuan University, Chengdu 610041, China., Zhang J; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Zhang M; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Department of Orthopaedic Surgery, The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, China., He F; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Medicine; and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400016, China., Mao Y; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Department of Orthopaedic Surgery, The Affiliated Zhongnan Hospital of Wuhan University, Wuhan 430072, China., Ding H; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Department of Orthopaedic Surgery, BenQ Medical Center Affiliated with Nanjing Medical University, Nanjing 210000, China., Zhang Y; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Department of Orthopaedic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266061, China., Niu C; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA.; Departments of Orthopaedic Surgery and Laboratory Medicine, Chongqing General Hospital, Chongqing 400013, China., Haydon RC; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA., Luu HH; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA., Lee MJ; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA., Wolf JM; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA., Shao Z; Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China., He TC; Molecular Oncology Laboratory, Department of Orthopaedic Surgery and Rehabilitation Medicine, The University of Chicago Medical Center, Chicago, IL 60637, USA. |
| المصدر: | Aging [Aging (Albany NY)] 2019 Dec 11; Vol. 11 (24), pp. 12476-12496. Date of Electronic Publication: 2019 Dec 11. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Albany, NY : Impact Journals, LLC |
| مواضيع طبية MeSH: | RNA, Long Noncoding*, Growth Differentiation Factor 2/*metabolism , Mesenchymal Stem Cells/*physiology , Osteogenesis/*physiology , Receptors, Notch/*metabolism, Cell Differentiation ; Growth Differentiation Factor 2/genetics ; HEK293 Cells ; Humans ; Receptors, Notch/genetics ; Transfection |
| مستخلص: | Understanding the bone and musculoskeletal system is essential to maintain the health and quality of life of our aging society. Mesenchymal stem cells (MSCs) can undergo self-renewal and differentiate into multiple tissue types including bone. We demonstrated that BMP9 is the most potent osteogenic factors although molecular mechanism underlying BMP9 action is not fully understood. Long noncoding RNAs (lncRNAs) play important regulatory roles in many physiological and/or pathologic processes. Here, we investigated the role of lncRNA Rmst in BMP9-induced osteogenic differentiation of MSCs. We found that Rmst was induced by BMP9 through Smad signaling in MSCs. Rmst knockdown diminished BMP9-induced osteogenic, chondrogenic and adipogenic differentiation in vitro, and attenuated BMP9-induced ectopic bone formation. Silencing Rmst decreased the expression of Notch receptors and ligands. Bioinformatic analysis predicted Rmst could directly bind to eight Notch-targeting miRNAs, six of which were downregulated by BMP9. Silencing Rmst restored the expression of four microRNAs (miRNAs). Furthermore, an activating Notch mutant NICD1 effectively rescued the decreased ALP activity caused by Rmst silencing. Collectively, our results strongly suggest that the Rmst-miRNA-Notch regulatory axis may play an important role in mediating BMP9-induced osteogenic differentiation of MSCs. |
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| معلومات مُعتمدة: | P30 CA014599 United States CA NCI NIH HHS; R21 CA226303 United States CA NCI NIH HHS; T32 GM007281 United States GM NIGMS NIH HHS; UL1 TR000430 United States TR NCATS NIH HHS |
| فهرسة مساهمة: | Keywords: BMP9; lncRNA Rmst; long noncoding RNAs; mesenchymal stem cells; miRNAs |
| المشرفين على المادة: | 0 (GDF2 protein, human) 0 (Growth Differentiation Factor 2) 0 (RNA, Long Noncoding) 0 (Receptors, Notch) |
| تواريخ الأحداث: | Date Created: 20191212 Date Completed: 20201110 Latest Revision: 20240327 |
| رمز التحديث: | 20240327 |
| مُعرف محوري في PubMed: | PMC6949095 |
| DOI: | 10.18632/aging.102583 |
| PMID: | 31825894 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1945-4589 |
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| DOI: | 10.18632/aging.102583 |