Generic placeholder image

Current Pharmaceutical Design

Author(s): Zhibo Sun, Fei Wu*, Yue Yang, Feng Liu, Fengbo Mo, Jin Chen, Guangyong Wang and Bo Zhang*

DOI: 10.2174/1381612825666190930094019

DownloadDownload PDF Flyer Cite As
MiR-144-3p Inhibits BMSC Proliferation and Osteogenic Differentiation Via Targeting FZD4 in Steroid-Associated Osteonecrosis

Page: [4806 - 4812] Pages: 7

  • * (Excluding Mailing and Handling)

Explore Articles
About Journal
For Authors
For Editors
For Reviewers

Abstract

Background: MicroRNAs have recently been recognized to be engaged in the development of bone diseases.

Objective: This study was performed to elucidate the effects of miR-144-3p on proliferation and osteogenesis of mesenchymal stem cells (MSCs) from the patients with steroid-associated osteonecrosis (ONFH) and its related mechanism.

Method: The expression level of miR-144-3p in the MSCs from the proximal femur of the patients was examined by Real-time PCR. The cell proliferation ability was assayed by MTT. The differentiation ability of MSCs was assayed by Alizarin Red S (ARS) staining. The interaction between miR-144-3p and frizzled4 (FZD4) was investigated by Real-time PCR, western blot and luciferase reporter assay.

Results: ONFH samples had the obviously high expression of miR-144-3p compared to the control. MiR-144-3p had a negative effect on the proliferation and osteogenesis of MSCs. Via targeting FZD4, miR-144-3p decreased β-catenin nuclear translocation, the transcription of RUNX2 and COL1A1. Over-expression of FZD4 partially reversed miR-144-3p-induced decrease in the proliferation and osteogenesis of MSCs.

Conclusion: MiR-144-3p might play an important role in the development of ONFH and might be used as a novel class of therapeutic targets for this disease.

Keywords: MiR-144-3p, FZD4, Steroid-associated osteonecrosis, Mesenchymal stem cells, ONFH, Real-time PCR.

[1]
Sun Z, Yang S, Ye S, et al. Aberrant CpG islands’ hypermethylation of ABCB1 in mesenchymal stem cells of patients with steroid-associated osteonecrosis. J Rheumatol 2013; 40(11): 1913-20.
[http://dx.doi.org/10.3899/jrheum.130191] [PMID: 24037553]
[2]
Sun ZB, Wang JW, Xiao H, et al. Icariin may benefit the mesenchymal stem cells of patients with steroid-associated osteonecrosis by ABCB1-promoter demethylation: a preliminary study. Osteoporos Int 2015; 26(1): 187-97.
[http://dx.doi.org/10.1007/s00198-014-2809-z] [PMID: 25112719]
[3]
Ahmed FE, Ahmed NC, Vos PW, et al. Diagnostic microRNA markers to screen for sporadic human colon cancer in stool: I. Proof of principle. Cancer Genomics Proteomics 2013; 10(3): 93-113.
[PMID: 23741026]
[4]
van Wijnen AJ, van de Peppel J, van Leeuwen JP, et al. MicroRNA functions in osteogenesis and dysfunctions in osteoporosis. Curr Osteoporos Rep 2013; 11(2): 72-82.
[http://dx.doi.org/10.1007/s11914-013-0143-6] [PMID: 23605904]
[5]
Liu P. MicroRNA expression analysis: next-generation sequencing. Methods Mol Biol 2018; 1783: 171-83.
[http://dx.doi.org/10.1007/978-1-4939-7834-2_8] [PMID: 29767362]
[6]
Lewis BP, Burge CB, Bartel DP. Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 2005; 120(1): 15-20.
[http://dx.doi.org/10.1016/j.cell.2004.12.035] [PMID: 15652477]
[7]
Bian Y, Qian W, Li H, Zhao RC, Shan WX, Weng X. Pathogenesis of glucocorticoid-induced avascular necrosis: a microarray analysis of gene expression in vitro. Int J Mol Med 2015; 36(3): 678-84.
[http://dx.doi.org/10.3892/ijmm.2015.2273] [PMID: 26151338]
[8]
Hao C, Yang S, Xu W, et al. MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3. Sci Rep 2016; 6: 22599.
[http://dx.doi.org/10.1038/srep22599] [PMID: 26932538]
[9]
Li Z, Yang B, Weng X, Tse G, Chan MTV, Wu WKK. Emerging roles of MicroRNAs in osteonecrosis of the femoral head. Cell Prolif 2018; 51(1): 12405.
[http://dx.doi.org/10.1111/cpr.12405] [PMID: 29131454]
[10]
Wang B, Yu P, Li T, Bian Y, Weng X. MicroRNA expression in bone marrow mesenchymal stem cells from mice with steroid-induced osteonecrosis of the femoral head. Mol Med Rep 2015; 12(5): 7447-54.
[http://dx.doi.org/10.3892/mmr.2015.4386] [PMID: 26459755]
[11]
Sun YX, Zhang JF, Xu J, et al. MicroRNA-144-3p inhibits bone formation in distraction osteogenesis through targeting Connexin 43. Oncotarget 2017; 8(52): 89913-22.
[http://dx.doi.org/10.18632/oncotarget.20984] [PMID: 29163798]
[12]
Wang C, He H, Wang L, Jiang Y, Xu Y. Reduced miR-144-3p expression in serum and bone mediates osteoporosis pathogenesis by targeting RANK. Biochem Cell Biol 2018; 96(5): 627-35.
[http://dx.doi.org/10.1139/bcb-2017-0243] [PMID: 29334613]
[13]
Zheng H, Guo Z, Zheng X, et al. MicroRNA-144-3p inhibits cell proliferation and induces cell apoptosis in prostate cancer by targeting CEP55. Am J Transl Res 2018; 10(8): 2457-68.
[14]
Cheng ZX, Song YX, Wang ZY, Wang Y, Dong Y. miR-144-3p serves as a tumor suppressor by targeting FZD7 and predicts the prognosis of human glioblastoma. Eur Rev Med Pharmacol Sci 2017; 21(18): 4079-86.
[PMID: 29028093]
[15]
Li J, Sun P, Yue Z, Zhang D, You K, Wang J. miR-144-3p induces cell cycle arrest and apoptosis in pancreatic cancer cells by targeting proline-rich protein 11 expression via the mitogen-activated protein kinase signaling pathway. DNA Cell Biol 2017; 36(8): 619-26.
[http://dx.doi.org/10.1089/dna.2017.3656] [PMID: 28574724]
[16]
Zhao Y, Xie Z, Lin J, Liu P. MiR-144-3p inhibits cell proliferation and induces apoptosis in multiple myeloma by targeting c-Met. Am J Transl Res 2017; 9(5): 2437-46.
[PMID: 28559994]
[17]
Li Y, Jin D, Xie W, et al. PPAR-γ and Wnt regulate the differentiation of MSCs into adipocytes and osteoblasts respectively. Curr Stem Cell Res Ther 2018; 13(3): 185-92.
[http://dx.doi.org/10.2174/1574888X12666171012141908] [PMID: 29034841]
[18]
Li R, Xu J, Wong DSH, Li J, Zhao P, Bian L. Self-assembled N-cadherin mimetic peptide hydrogels promote the chondrogenesis of mesenchymal stem cells through inhibition of canonical Wnt/β-catenin signaling. Biomaterials 2017; 145: 33-43.
[http://dx.doi.org/10.1016/j.biomaterials.2017.08.031] [PMID: 28843065]
[19]
Long H, Sun B, Cheng L, et al. miR-139-5p represses BMSC osteogenesis via targeting Wnt/β-Catenin signaling pathway. DNA Cell Biol 2017; 36(8): 715-24.
[http://dx.doi.org/10.1089/dna.2017.3657] [PMID: 28622009]
[20]
Fu HD, Wang BK, Wan ZQ, Lin H, Chang ML, Han GL. Wnt5a mediated canonical Wnt signaling pathway activation in orthodontic tooth movement: possible role in the tension force-induced bone formation. J Mol Histol 2016; 47(5): 455-66.
[http://dx.doi.org/10.1007/s10735-016-9687-y] [PMID: 27456852]
[21]
Koo KH, Kim R, Kim YS, et al. Risk period for developing osteonecrosis of the femoral head in patients on steroid treatment. Clin Rheumatol 2002; 21(4): 299-303.
[http://dx.doi.org/10.1007/s100670200078] [PMID: 12189457]
[22]
Sun Z, Zhang Y, Yang S, et al. Growth differentiation factor 5 modulation of chondrogenesis of self-assembled constructs involves gap junction-mediated intercellular communication. Dev Growth Differ 2012; 54(9): 809-17.
[http://dx.doi.org/10.1111/dgd.12009] [PMID: 23121099]
[23]
Yu WH, Li FG, Chen XY, et al. PPARγ suppression inhibits adipogenesis but does not promote osteogenesis of human mesenchymal stem cells. Int J Biochem Cell Biol 2012; 44(2): 377-84.
[http://dx.doi.org/10.1016/j.biocel.2011.11.013] [PMID: 22120652]
[24]
Sun Z, Nair LS, Laurencin CT. The paracrine effect of adipose-derived stem cells inhibits IL-1β-induced inflammation in chondrogenic cells through the Wnt/β-Catenin signaling pathway. Regen Eng Transl Med 2018; 4: 35-41.
[http://dx.doi.org/10.1007/s40883-018-0047-1]
[25]
Zhang M, Li DH, Li F, et al. Integrated analysis of MiRNA and genes associated with meat quality reveals that Gga-MiR-140-5p affects intramuscular fat deposition in chickens. Cell Physiol Biochem 2018; 46(6): 2421-33.
[http://dx.doi.org/10.1159/000489649] [PMID: 29742492]
[26]
Sandiford OA, Moore CA, Du J, et al. Human aging and cancer: Role of miRNA in tumor microenvironment. Adv Exp Med Biol 2018; 1056: 137-52.
[http://dx.doi.org/10.1007/978-3-319-74470-4_9] [PMID: 29754179]
[27]
Yue J, Wan F, Zhang Q, et al. Effect of glucocorticoids on miRNA expression spectrum of rat femoral head microcirculation endothelial cells. Gene 2018; 651: 126-33.
[http://dx.doi.org/10.1016/j.gene.2018.01.057] [PMID: 29408208]
[28]
Gu C, Xu Y, Zhang S, et al. miR-27a attenuates adipogenesis and promotes osteogenesis in steroid-induced rat BMSCs by targeting PPARγ and GREM1. Sci Rep 2016; 6: 38491.
[http://dx.doi.org/10.1038/srep38491] [PMID: 27910957]
[29]
Yuan HF, Von Roemeling C, Gao HD, Zhang J, Guo CA, Yan ZQ. Analysis of altered microRNA expression profile in the reparative interface of the femoral head with osteonecrosis. Exp Mol Pathol 2015; 98(2): 158-63.
[http://dx.doi.org/10.1016/j.yexmp.2015.01.002] [PMID: 25612520]
[30]
Bullock WA, Robling AG. WNT-mediated modulation of bone metabolism: implications for WNT targeting to treat extraskeletal disorders. Toxicol Pathol 2017; 45(7): 864-8.
[http://dx.doi.org/10.1177/0192623317738170] [PMID: 29105581]
[31]
Li Y, Jin D, Xie W, et al. PPAR-γ and Wnt regulate the differentiation of MSCs into adipocytes and osteoblasts respectively. Curr Stem Cell Res Ther 2018; 13(3): 185-92.
[http://dx.doi.org/10.2174/1574888X12666171012141908] [PMID: 29034841]
[32]
Li R, Xu J, Wong DSH, Li J, Zhao P, Bian L. Self-assembled N-cadherin mimetic peptide hydrogels promote the chondrogenesis of mesenchymal stem cells through inhibition of canonical Wnt/β-catenin signaling. Biomaterials 2017; 145: 33-43.
[http://dx.doi.org/10.1016/j.biomaterials.2017.08.031] [PMID: 28843065]
[33]
Li JP, Zhuang HT, Xin MY, Zhou YL. MiR-214 inhibits human mesenchymal stem cells differentiating into osteoblasts through targeting β-catenin. Eur Rev Med Pharmacol Sci 2017; 21(21): 4777-83.
[PMID: 29164587]
[34]
Xu ML, Bi CWC, Liu EYL, Dong TTX, Tsim KWK. Wnt3a induces the expression of acetylcholinesterase during osteoblast differentiation via the Runx2 transcription factor. J Biol Chem 2017; 292(30): 12667-78.
[http://dx.doi.org/10.1074/jbc.M117.777581] [PMID: 28607150]