The Inhibition of MicroRNA-139-5p Promoted Osteoporosis of Bone Marrow-Derived Mesenchymal Stem Cells by Targeting Wnt/Beta- Catenin Signaling Pathway by NOTCH1

다국어 초록 (Multilingual Abstract)

We investigated the therapeutic effects of microRNA-139-5p in relation to osteoporosis of bone marrow-derived mesenchymal stem cell (BMSCs) and its underlying mechanisms. In this study we used a dexamethasone-induced in vivo model of osteoporosis and BMSCs were used for the in vitro model. Real-time quantitative polymerase chain reaction (RT-PCR) and gene chip were used to analyze the expression of microRNA-139-5p. In an osteoporosis rat model, the expression of microRNA-139-5p was increased, compared with normal group. Downregulation of microRNA-139-5p promotes cell proliferation and osteogenic differentiation in BMSCs. Especially, up-regulation of microRNA-139-5p reduced cell proliferation and osteogenic differentiation in BMSCs. Overexpression of miR-139-5p induced Wnt/β-catenin and down-regulated NOTCH1 signaling in BMSCs. Down-regulation of miR-139-5p suppressed Wnt/β-catenin and induced NOTCH1 signaling in BMSCs. The inhibition of NOTCH1 reduced the effects of anti-miR-139-5p on cell proliferation and osteogenic differentiation in BMSCs. Activation of Wnt/β-catenin also inhibited the effects of anti-miR-139-5p on cell proliferation and osteogenic differentiation in BMSCs. Taken together, our results suggested that the inhibition of microRNA-139-5p promotes osteogenic differentiation of BMSCs via targeting Wnt/β-catenin signaling pathway by NOTCH1.

참고문헌 (Reference)

1 Xu J, "miR-19b attenuates H2O2-induced apoptosis in rat H9C2cardiomyocytes via targeting PTEN" 7 : 10870-10878, 2016

2 Gao C, "The effects of intravenous hyperoxygenated solution infusion on systemic oxygenation and intrapulmonary shunt during one-lung ventilation in pigs" 159 : 653-659, 2010

3 Li J, "Targeting the Notch1 oncogene by miR-139-5p inhibits glioma metastasis and epithelial-mesenchymal transition(EMT)" 18 : 133-, 2018

4 Yang J, "Platelet-rich plasma protects rat chondrocytes from interleukin-1beta-induced apoptosis" 14 : 4075-4082, 2016

5 Li RK, "PTENP1acts as a ceRNA to regulate PTEN by sponging miR-19b and explores the biological role of PTENP1 in breast cancer" 24 : 309-315, 2017

6 Cui X, "Overexpression of microRNA-634 suppresses survival and matrix synthesis of human osteoarthritis chondrocytes by targeting PIK3R1" 6 : 23117-, 2016

7 Liang X, "MicroRNA-22 impairs anti-tumor ability of dendritic cells by targeting p38" 10 : e0121510-, 2015

8 Xie Y, "MicroRNA-139-5p elevates skeletal myogenic differentiation of human adult dental pulp stem cells through Wnt/beta-catenin signaling pathway" 16 : 2835-2842, 2018

9 Cong J, "MiR-634decreases cell proliferation and induces apoptosis by targeting mTOR signaling pathway in cervical cancer cells" 44 : 1694-1701, 2016

10 Li M, "LINC00152 promotes the growth and invasion of oral squamous cell carcinoma by regulating miR-139-5p" 11 : 6295-6304, 2018

11 Nagato AC, "Hyperoxia promotes polarization of the immune response in ovalbumin-induced airway inflammation, leading to a TH17 cell phenotype" 3 : 321-337, 2015

12 Rosario PW, "Follow-up of patients with low-risk papillary thyroid carcinoma and undetectable basal serum thyroglobulin after ablation measured with a sensitive assay : a prospective study" 45 : 911-914, 2013

13 Liu GL, "Effects of microRNA-19b on the proliferation, apoptosis, and migration of wilms’tumor cells via the PTEN/PI3K/AKT signaling pathway" 118 : 3424-3434, 2017

14 Fan P, "Effect of 1, 25-(OH)2D3 on proliferation of fibroblast-like synoviocytes and expressions of pro-inflammatory cytokines through regulating microRNA-22 in a rat model of rheumatoid arthritis" 42 : 145-155, 2017

15 Hong CM, "Distant metastatic lesions in patients with differentiated thyroid carcinoma. Clinical implications of radioiodine and FDG uptake" 52 : 121-129, 2013

16 Saric A, "Diminished resistance to hyperoxia in brains of reproductively senescent female CBA/H mice" 21 : 191-199, 2015

17 Jeansonne D, "Differential effects of microRNAs on glioblastoma growth and migration" 4 : 46-64, 2013

18 Liu H, "Development of marker genes for jasmonic acid signaling in shoots and roots of wheat" 11 : e1176654-, 2016

19 Li X, "Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation" 28 : 1553-1560, 2014

20 Yang J, "Cardioprotective effect of miRNA-22 on hypoxia/reoxygenation induced cardiomyocyte injury in neonatal rats" 579 : 17-22, 2016

21 Cabanillas ME, "Cabozantinib as salvage therapy for patients with tyrosine kinase inhibitor-refractory differentiated thyroid cancer : results of a multicenter phase II International thyroid oncology group trial" 35 : 3315-3321, 2017

22 Leslie WD, "Body mass and composition affect bone density in recently diagnosed inflammatory bowel disease : the manitoba IBD cohort study" 15 : 39-46, 2009

23 Xiang Y, "Association of miR-21, miR-126 and miR-605 gene polymorphisms with ischemic stroke risk" 8 : 95755-95763, 2017

24 Livak KJ, "Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T))" 25 : 402-408, 2001

25 Chow LQ, "A phase I study of pazopanib in combination with escalating doses of 131I in patients with well-differentiated thyroid carcinoma borderline refractory to radioiodine" 12 (12): e0178325-, 2017

26 Hsin-An Chang, "7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress" 대한신경정신의학회 13 (13): 531-540, 2016

27 Zhang L, "25-hydroxycholesterol promotes RANKL-induced osteoclastogenesis through coordinating NFATc1 and Sp1 complex in the transcription of miR-139-5p" 485 : 736-741, 2017