miR‑142‑3p promotes osteoblast differentiation by modulating Wnt signaling

Hu,Weihua; Ye,Yaping; Zhang,Weikai; Wang,Jiang; Chen,Anmin; Guo,Fengjing

doi:10.3892/mmr.2012.1207

miR‑142‑3p promotes osteoblast differentiation by modulating Wnt signaling

Authors:
- Weihua Hu
- Yaping Ye
- Weikai Zhang
- Jiang Wang
- Anmin Chen
- Fengjing Guo
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Affiliations: Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P.R. China
Published online on: November 28, 2012 https://doi.org/10.3892/mmr.2012.1207
Pages: 689-693

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Abstract

Canonical Wnt signaling is critical for the control of osteoblast differentiation in human mesenchymal stem cells. MicroRNAs (miRs) are essential regulators of cell differentiation by post‑transcriptional regulation of target gene expression. The aim of the present study was to investigate the molecular mechanism by which miR‑142‑3p promotes osteoblastic differentiation using the human fetal osteoblastic 1.19 (hFOB1.19), real-time PCR and western blot analysis. Results showed an increased expression of miR‑142‑3p during osteoblast differentiation in the mesenchymal precursor cell line, hFOB1.19. In addition, the ectopic overexpression of miR‑142‑3p promoted hFOB1.19 differentiation, whereas the inhibition of miR‑142‑3p repressed differentiation. The expression of miR‑142‑3p was positively correlated with β‑catenin, an important protein in Wnt signaling. The adenomatous polyposis coli (APC) gene was a direct target of miR‑142‑3p, whereby miR‑142‑3p promoted Wnt signaling through inhibition of APC, leading to accumulation and nuclear translocation of β‑catenin. Therefore, miR‑142‑3p may be an essential mediator of osteoblast differentiation and a new therapeutic strategy for osteogenesis disorders.

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1	Kang SK, Shin IS, Ko MS, Jo JY and Ra JC: Journey of mesenchymal stem cells for homing: strategies to enhance efficacy and safety of stem cell therapy. Stem Cells Int. 2012:3429682012.PubMed/NCBI
2	Lian JB, Stein GS, van Wijnen AJ, et al: MicroRNA control of bone formation and homeostasis. Nat Rev Endocrinol. 8:212–227. 2012. View Article : Google Scholar : PubMed/NCBI
3	Suzuki D, Yamada A, Aizawa R, et al: BMP2 differentially regulates the expression of Gremlin1 and Gremlin2, the negative regulators of BMP function, during osteoblast differentiation. Calcif Tissue Int. 91:88–96. 2012. View Article : Google Scholar : PubMed/NCBI
4	Huang J, Zhao L, Xing L and Chen D: MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 28:357–364. 2009.PubMed/NCBI
5	Song L, Liu M, Ono N, Bringhurst FR, Kronenberg HM and Guo J: Loss of wnt/β-catenin signaling causes cell fate shift of preosteoblasts from osteoblasts to adipocytes. J Bone Miner Res. Jun 22–2012.(Epub ahead of print).
6	Kapinas K, Kessler C, Ricks T, Gronowicz G and Delany AM: miR-29 modulates Wnt signaling in human osteoblasts through a positive feedback loop. J Biol Chem. 285:25221–25231. 2010. View Article : Google Scholar : PubMed/NCBI
7	Herr P, Hausmann G and Basler K: WNT secretion and signalling in human disease. Trends Mol Med. 18:483–493. 2012. View Article : Google Scholar : PubMed/NCBI
8	Pritchard CC, Cheng HH and Tewari M: MicroRNA profiling: approaches and considerations. Nat Rev Genet. 13:358–369. 2012. View Article : Google Scholar : PubMed/NCBI
9	Eskildsen T, Taipaleenmaki H, Stenvang J, et al: MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo. Proc Natl Acad Sci USA. 108:6139–6144. 2011. View Article : Google Scholar : PubMed/NCBI
10	Li Z, Hassan MQ, Jafferji M, et al: Biological functions of miR-29b contribute to positive regulation of osteoblast differentiation. J Biol Chem. 284:15676–15684. 2009. View Article : Google Scholar : PubMed/NCBI
11	Wang T and Xu Z: miR-27 promotes osteoblast differentiation by modulating Wnt signaling. Biochem Biophys Res Commun. 402:186–189. 2010. View Article : Google Scholar : PubMed/NCBI
12	Wang XS, Gong JN, Yu J, et al: MicroRNA-29a and microRNA- 142-3p are regulators of myeloid differentiation and acute myeloid leukemia. Blood. 119:4992–5004. 2012. View Article : Google Scholar : PubMed/NCBI
13	Jin HL, Kim JS, Kim YJ, Kim SJ, Broxmeyer HE and Kim KS: Dynamic expression of specific miRNAs during erythroid differentiation of human embryonic stem cells. Mol Cells. 34:177–183. 2012. View Article : Google Scholar : PubMed/NCBI
14	Qiu W, Hu Y, Andersen TE, et al: Tumor necrosis factor receptor superfamily member 19 (TNFRSF19) regulates differentiation fate of human mesenchymal (stromal) stem cells through canonical Wnt signaling and C/EBP. J Biol Chem. 285:14438–14449. 2010. View Article : Google Scholar
15	Zhu HC, Wang LM, Wang M, et al: MicroRNA-195 downregulates Alzheimer’s disease amyloid-β production by targeting BACE1. Brain Res Bull. 88:596–601. 2012.PubMed/NCBI
16	Abdallah BM, Haack-Sorensen M, Burns JS, et al: Maintenance of differentiation potential of human bone marrow mesenchymal stem cells immortalized by human telomerase reverse transcriptase gene despite [corrected] extensive proliferation. Biochem Biophys Res Commun. 326:527–538. 2005.PubMed/NCBI
17	Akiyama T: Wnt/beta-catenin signaling. Cytokine Growth Factor Rev. 11:273–282. 2000. View Article : Google Scholar
18	Wang F, Wang XS, Yang GH, et al: miR-29a and miR-142-3p downregulation and diagnostic implication in human acute myeloid leukemia. Mol Biol Rep. 39:2713–2722. 2011. View Article : Google Scholar : PubMed/NCBI
19	Perri R, Nares S, Zhang S, Barros SP and Offenbacher S: MicroRNA modulation in obesity and periodontitis. J Dent Res. 91:33–38. 2011. View Article : Google Scholar
20	Kim D, Song J, Kim S, Kang SS and Jin EJ: MicroRNA-142-3p regulates TGF-β3-mediated region-dependent chondrogenesis by regulating ADAM9. Biochem Biophys Res Commun. 414:653–659. 2011.PubMed/NCBI
21	Waaler J, Machon O, Tumova L, et al: A novel tankyrase inhibitor decreases canonical Wnt signaling in colon carcinoma cells and reduces tumor growth in conditional APC mutant mice. Cancer Res. 72:2822–2832. 2012. View Article : Google Scholar : PubMed/NCBI