MicroRNA-21 promotes osteogenic differentiation by targeting small mothers against decapentaplegic 7

Li,Hongqiu; Yang,Feng; Wang,Zhe; Fu,Qin; Liang,A

doi:10.3892/mmr.2015.3497

MicroRNA-21 promotes osteogenic differentiation by targeting small mothers against decapentaplegic 7

Authors:
- Hongqiu Li
- Feng Yang
- Zhe Wang
- Qin Fu
- A Liang
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Affiliations: Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang 110004, P.R. China, Department of Radiology, Central Hospital of Shenyang Medical College, Shenyang 110024, P.R. China, Department of Blood Transfusion, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Orthopedics, Central Hospital of Shenyang Medical College, Shenyang 110024, P.R. China
Published online on: March 17, 2015 https://doi.org/10.3892/mmr.2015.3497
Pages: 1561-1567

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Abstract

Previous studies have suggested that microRNAs (miRNAs/miRs) may positively or negatively control osteogenic differentiation and mineralization by targeting negative regulators of osteogenesis or important osteogenic factors. miR‑21 is important in osteoblast differentiation and Smad7 is a critical regulator of osteogenic differentiation, which inhibits proliferation, differentiation and mineralization in mouse osteoblast cells. However, the association between Smad7 and miR‑21 remain to be elucidated. In the present study, miR‑21 was found to promote the level of osteogenic differentiation and increase matrix mineralization in MC3T3‑E1 cells. Furthermore, Smad7 was identified as a direct target of miR‑21 in the MC3T3‑E1 cells. The overexpression of miR‑21 affected the protein levels of SMAD7, but not the mRNA levels, which suggested that miR‑21 regulates the levels of SMAD7 by inhibiting translation, rather than by promoting mRNA decay. Forced expression of miR‑21 promoted osteogenic differentiation and mineralization, while inhibition of miR‑21 suppressed these processes. The present study also identified for the first time, to the best of our knowledge, the promotion of osteogenic differentiation and mineralization by miR‑21, by repressing the expression of Smad7.

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1	Moore BT and Xiao P: MiRNAs in bone diseases. Microrna. 2:20–31. 2013. View Article : Google Scholar : PubMed/NCBI
2	Lian JB, Stein GS, van Wijnen AJ, Stein JL, Hassan MQ, Gaur T and Zhang Y: MicroRNA control of bone formation and homeostasis. Nat Rev Endocrinol. 8:212–227. 2012. View Article : Google Scholar : PubMed/NCBI
3	Kureel J, Dixit M, Tyagi AM, Mansoori MN, Srivastava K, Raghuvanshi A, Maurya R, Trivedi R, Goel A and Singh D: miR-542-3p suppresses osteoblast cell proliferation and differentiation, targets BMP-7 signaling and inhibits bone formation. Cell Death Dis. 5:e10502014. View Article : Google Scholar : PubMed/NCBI
4	Lin X, Wu L, Zhang Z, Yang R, Guan Q, Hou X and Wu Q: MiR-335-5p promotes chondrogenesis in mouse mesenchymal stem cells and is regulated through two positive feedback loops. J Bone Miner Res. 29:1575–1585. 2014. View Article : Google Scholar
5	Vimalraj S, Partridge NC and Selvamurugan N: A Positive Role of microRNA-15b on regulation of osteoblast differentiation. J Cell Physiol. 29:1236–1244. 2014. View Article : Google Scholar
6	Chen G, Deng C and Li YP: TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci. 8:272–288. 2012. View Article : Google Scholar
7	Lei Z, Xu G, Wang L, Yang H, Liu X, Zhao J and Zhang HT: MiR-142-3p represses TGF-β-induced growth inhibition through repression of TGFβR1 in non-small cell lung cancer. FASEB J. 28:2696–2704. 2014. View Article : Google Scholar : PubMed/NCBI
8	Cao S, Xiao L, Rao JN, Zou T, Liu L, Zhang D, Turner DJ, Gorospe M and Wang JY: Inhibition of Smurf2 translation by miR-322/503 modulates TGF-β/Smad2 signaling and intestinal epithelial homeostasis. Mol Biol Cell. 25:1234–1243. 2014. View Article : Google Scholar : PubMed/NCBI
9	Yano M, Inoue Y, Tobimatsu T, Hendy G, Canaff L, Sugimoto T, Seino S and Kaji H: Smad7 inhibits differentiation and mineralization of mouse osteoblastic cells. Endocr J. 59:653–662. 2012. View Article : Google Scholar : PubMed/NCBI
10	Kupczyk M and Kuna P: MicroRNAs-new biomarkers of respiratory tract diseases. Pneumonol Alergol Pol. 82:183–190. 2014.In Polish. View Article : Google Scholar
11	Fan X, Wang E, Wang X, Cong X and Chen X: MicroRNA-21 is a unique signature associated with coronary plaque instability in humans by regulating matrix metalloproteinase-9 via reversion-inducing cysteine-rich protein with Kazal motifs. Exp Mol Pathol. 96:242–249. 2014. View Article : Google Scholar : PubMed/NCBI
12	Liu H, Huang X, Liu X, Xiao S, Zhang Y, Xiang T, Shen X, Wang G and Sheng B: mir-21 promotes human nucleus pulposus cell proliferation through PTEN/AKT signaling. Int J Mol Sci. 15:4007–4018. 2014. View Article : Google Scholar : PubMed/NCBI
13	Yang N, Wang G, Hu C, Shi Y, Liao L, Shi S, Cai Y, Cheng S, Wang X, Liu Y, Tang L, et al: Tumor necrosis factor α suppresses the mesenchymal stem cell osteogenesis promoter miR-21 in estrogen deficiency-induced osteoporosis. J Bone Miner Res. 28:559–573. 2013. View Article : Google Scholar
14	Yuan JS, Reed A, Chen F and Stewart CN Jr: Statistical analysis of real-time PCR data. BMC Bioinformatics. 7:852006. View Article : Google Scholar : PubMed/NCBI
15	van Wijnen AJ, van de Peppel J, van Leeuwen JP, et al: MicroRNA functions in osteogenesis and dysfunctions in osteoporosis. Curr Osteoporos Rep. 11:72–82. 2013. View Article : Google Scholar : PubMed/NCBI
16	Salaun B, Yamamoto T, Badran B, et al: Differentiation associated regulation of microRNA expression in vivo in human CD8+ T cell subsets. J Transl Med. 9:442011. View Article : Google Scholar : PubMed/NCBI
17	Ren W, Wang X, Gao L, Li S, Yan X, Zhang J, Huang C, Zhang Y and Zhi K: MiR-21 modulates chemosensitivity of tongue squamous cell carcinoma cells to cisplatin by targeting PDCD4. Mol Cell Biochem. 390:253–262. 2014. View Article : Google Scholar : PubMed/NCBI
18	Liu C, Li B, Cheng Y, Lin J, Hao J, Zhang S, Mitchel RE, Sun D, Ni J, Zhao L, Gao F, et al: MiR-21 plays an important role in radiation induced carcinogenesis in BALB/c mice by directly targeting the tumor suppressor gene Big-h3. Int J Biol Sci. 7:347–363. 2011. View Article : Google Scholar : PubMed/NCBI
19	Chan JK, Blansit K, Kiet T, Sherman A, Wong G, Earle C and Bourguignon LY: The inhibition of miR-21 promotes apoptosis and chemosensitivity in ovarian cancer. Gynecol Oncol. 132:739–744. 2014. View Article : Google Scholar : PubMed/NCBI
20	Eguchi T, Watanabe K, Hara ES, Ono M, Kuboki T and Calderwood SK: OstemiR: a novel panel of microRNA biomarkers in osteoblastic and osteocytic differentiation from mesencymal stem cells. PLoS One. 8:e587962013. View Article : Google Scholar : PubMed/NCBI
21	Luo L, Li N, Lv N and Huang D: SMAD7: a timer of tumor progression targeting TGF-β signaling. Tumour Biol. 35:8379–8385. 2014. View Article : Google Scholar : PubMed/NCBI
22	Wang W, Olson D, Liang G, Franceschi RT, Li C, Wang B, Wang SS and Yang S: Collagen XXIV (Col24α1) promotes osteoblastic differentiation and mineralization through TGF-β/Smads signaling pathway. Int J Biol Sci. 8:1310–1322. 2012. View Article : Google Scholar
23	Li Q, Zhang D, Wang Y, Sun P, Hou X, Larner J, Xiong W and Mi J: MiR-21/Smad 7 signaling determines TGF-β1-induced CAF formation Sci Rep. 3:20382013.
24	Zhu H, Luo H, Li Y, Zhou Y, Jiang Y, Chai J, Xiao X, You Y and Zuo X: MicroRNA-21 in scleroderma fibrosis and its function in TGF-β-regulated fibrosis-related genes expression. J Clin Immunol. 33:1100–1109. 2013. View Article : Google Scholar : PubMed/NCBI
25	Bhagat TD, Zhou L, Sokol L, et al: miR-21 mediates hematopoietic suppression in MDS by activating TGF-β signaling. Blood. 121:2875–2881. 2013. View Article : Google Scholar : PubMed/NCBI
26	Chung AC, Dong Y, Yang W, Zhong X, Li R and Lan HY: Smad7 suppresses renal fibrosis via altering expression of TGF-β/Smad3-regulated microRNAs. Mol Ther. 21:388–398. 2013. View Article : Google Scholar :