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Cellular and Molecular Biology Letters

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Volume 20, Issue 4


Mechanical strain affects some microRNA profiles in pre-oeteoblasts.

Yang Wang / Xianqiong Zou / Yong Guo
  • Corresponding author
  • College of Biotechnology, Guilin Medical University, Guilin, 541004, Guangxi, China
  • Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Institute of Biophysics, Dezhou University, Dezhou, China
  • Institute of Medical Equipment, Academy of Military Medical Sciences, Tianjin 300161, China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Lu Wang / Yongming Liu / Qiangcheng Zeng
  • Shandong Provincial Key Laboratory of Functional Macromolecular Biophysics, Institute of Biophysics, Dezhou University, Dezhou, China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Xizheng Zhang
Published Online: 2015-10-15 | DOI: https://doi.org/10.1515/cmble-2015-0034


MicroRNAs (miRNAs) are important regulators of cell proliferation, differentiation and function. Mechanical strain is an essential factor for osteoblast proliferation and differentiation. A previous study revealed that a physiological mechanical tensile strain of 2500 microstrain (με) at 0.5 Hz applied once a day for 1 h over 3 consecutive days promoted osteoblast differentiation. However, the mechanoresponsive miRNAs of these osteoblasts were not identified. In this study, we applied the same mechanical tensile strain to in vitro cultivated mouse MC3T3-E1 pre-osteoblasts and identified the mechanoresponsive miRNAs. Using miRNA microarray and qRT-PCR assays, the expression patterns of miRNAs were evaluated and 5 of them were found to be significantly different between the mechanical loading group and the control group: miR-3077-5p, 3090-5p and 3103-5p were significantly upregulated and miR-466i-3p and 466h-3p were downregulated. Bioinformatics analysis revealed possible target genes for these differentially expressed miRNAs. Some target genes correlated with osteoblast differentiation. These findings indicated that the mechanical strain changed the expression levels of these miRNAs. This might be a potential regulator of osteoblast differentiation and responses to mechanical strain.

Keywords: Mechanical strain; 2500 microstrain (με); Mouse MC3T3-E1 preosteoblasts; MicroRNA; Osteoblast differentiation; Microarray; qRT-PCR; Bioinformatics; Regulator; Mechanoresponsive


  • 1. Gordeladze, J.O., Djouad, F., Brondello, J.M., Noël. D., Richard, D.I., Apparailly, F. and Jorgensen, C. Concerted stimuli regulating osteo-chondral differentiation from stem cells: phenotype acquisition regulated by microRNAs. Acta Pharmacol. Sin. 30 (2009) 1369-1384. DOI: 10.1038/aps.2009.143.Web of ScienceCrossrefGoogle Scholar

  • 2. Neve, A., Corrado, A. and Cantatore, F.P. Osteocytes: central conductors of bone biology in normal and pathological conditions. Acta Physiol. 204 (2012) 317-330. DOI: 10.1111/j.1748-1716.2011.02385.x.CrossrefWeb of ScienceGoogle Scholar

  • 3. Chung, E. and Rylander, M.N. Response of a preosteoblastic cell line to cyclic tensile stress conditioning and growth factors for bone tissue engineering. Tissue Eng. 18 (2011) 397-410. DOI: 10.1089/ ten.tea.2010.0414.Web of ScienceCrossrefGoogle Scholar

  • 4. Lim, J.Y., Loiselle, A.E., Lee, J.S., Zhang, Y., Salvi, J.D. and Donahue, H.J. Optimizing the osteogenic potential of adult stem cells for skeletal regeneration. J. Orthop. Res. 29 (2011) 1627-1633. DOI: 10.1002/jor.21441.Web of ScienceCrossrefGoogle Scholar

  • 5. Lin, G.L. and Hankenson, K.D. Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J. Cell. Biochem. 112 (2011) 3491-3501. DOI: 10.1002/jcb.23287.Web of ScienceCrossrefGoogle Scholar

  • 6. Jacobsa, C., Grimma, S., Ziebartb, T., Walterb, C. and Wehrbeina, H. Osteogenic differentiation of periodontal fibroblasts is dependent on the strength of mechanical strain. Arch. Oral Biol. 58 (2013) 896-904. DOI: 10.1016/j.archoralbio.2013.01.009.CrossrefWeb of ScienceGoogle Scholar

  • 7. Kaneuji, T., Nogami, S., Ariyoshi, W., Nishihara, T. and Takahashi, T. Regulatory effect on osteoclastogenesis of mechanical strain-loaded osteoblasts. J. Oral Maxillofac. Surg. 40 (2011) 1215-1215. DOI: 10.1016/j.ijom.2011.07.640.CrossrefGoogle Scholar

  • 8. Rumney, R., Sunters, A., Reilly, G. and Gartland, A. Application of multiple forms of mechanical loading to human osteoblasts reveals increased ATP release in response to fluid flow in 3D cultures and differential regulation of immediate early genes. J. Biomech. 45 (2012) 549-554. DOI: 10.1016/j.jbiomech.2011.11.036.CrossrefWeb of ScienceGoogle Scholar

  • 9. Vimalraj, S. and Selvamurugan, N. MicroRNAs: synthesis, gene regulation and osteoblast differentiation. Curr. Issues Mol. Biol. 15 (2012) 7-18.Google Scholar

  • 10. Taipaleenmäki, H., Hokland, L.B., Chen, L., Kauppinen, S. and Kassem, M. Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation. Eur. J. Endocrinol. 166 (2012) 359-371. DOI: 10.1530/EJE-11-0646.CrossrefGoogle Scholar

  • 11. Fang , Y . and Gao, W. Roles of microRNAs during prostatic tumorigenesis and tumor progression. Oncogene 33 (2013) 135-147. DOI: 10.1038/onc.2013.54. Web of ScienceCrossrefGoogle Scholar

  • 12. Cheung, K.C., Sposito, N, Stumpf, P.S., Wilson, D.I., Sanchez-Elsner, T. and Oreffo, R.C. MicroRNA-146a regulates human foetal femur derived skeletal stem cell differentiation by downregulating SMAD2 and SMAD3. PloS One 9 (2014) e98063. DOI: 10.1371/journal.pone.0098063.CrossrefGoogle Scholar

  • 13. Huang, J., Zhao, L., Xing, L. and Chen, D. MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells 28 (2010) 357-364. DOI: 10.1002/stem.288.CrossrefGoogle Scholar

  • 14. Ivey, K.N. and Srivastava, D. MicroRNAs as regulators of differentiation and cell fate decisions. Cell 7 (2010) 36-41. DOI: 10.1016/ j.stem.2010.06.012.CrossrefGoogle Scholar

  • 15. Taipaleenmäki, H., Hokland, L.B., Chen, L., Kauppinen, S. and Kassem, M. Mechanisms in endocrinology: micro-RNAs: targets for enhancing osteoblast differentiation and bone formation. Eur. J. Endocrinol. 166 (2012) 359-371. DOI: 10.1530/EJE-11-0646.CrossrefGoogle Scholar

  • 16. Liu, L., Guo, Y., Wan, Z., Shi, C., Li, L., Li, R., Hao, Q., Li, H., Zhang, X. Effects of phytoestrogen a-ZAL and mechanical stimulation proliferation, osteoblastic differentiation, and OPG/RANKL expression in MC3T3-E1 pre-osteoblasts. Cell. Mol. Bioeng. 5 (2012) 427-439. DOI:10.1007/ s12195-012-0244-9.CrossrefWeb of ScienceGoogle Scholar

  • 17. Guo, Y., Zhang, C., Zeng, Q., Li, R., Liu, L., Hao, Q., Shi, C., Zhang, X. and Yan, Y. Mechanical strain promotes osteoblast ECM formation and improves its osteoinductive potential. Biomed. Eng. Online 11 (2012) 80. DOI: 10.1186/1475-925X-11-80.Web of ScienceCrossrefGoogle Scholar

  • 18. Flieger, J., Karachalios, T., Khaldi, L., Raptou, P. and Lyritis, G. Mechanical stimulation in the form of vibration prevents postmenopausal bone loss in ovariectomized rats. Calcif. Tissue Int. 63 (1998) 510-514. DOI: 10.1007/s002239900566.CrossrefGoogle Scholar

  • 19. Rubin, C.T. and Lanyon, L.E. Regulation of bone formation by applied dynamic loads. J. Bone Joint Surg. Am. 66 (1984) 397-402. DOI: 10.1007/978-1-4471-5451-8_134.CrossrefGoogle Scholar

  • 20. Lee, K., Jessop, H., Suswillo, R., Zaman, G. and Lanyon, L. Endocrinology: bone adaptation requires oestrogen receptor-α. Nature 424 (2003) 389-389. DOI:10.1038/424389a.CrossrefGoogle Scholar

  • 21. Brunski, J.B. In vivo bone response to biomechanical loading at the bone/dental-implant interface. Adv. Dent. Res. 13 (1999) 99-119. DOI: 10.1177/08959374990130012301.CrossrefGoogle Scholar

  • 22. Onal, M., Piemontese, M., Xiong, J, Wang, Y., Li, H., Ye, S., Komatsu, M., Selig, M., Weinstein, R.S., Zhao, H., Jilka, R.L., Almeida, M., Manolagas, S.C. and O’Brien, C.A. Suppression of autophagy in osteocytes mimics skeletal aging. J. Biol. Chem. 288 (2013) 17432-17440. DOI: 10.1177/ 08959374990130012301.CrossrefWeb of ScienceGoogle Scholar

  • 23. Wang, L., Zhang, X., Guo, Y., Chen, X., Li, R., Liu, L., Shi, C., Guo, C. and Zhang, Y. Involvement of BMPs/Smad signaling pathway in mechanical response in osteoblasts. Cell. Physiol. Biochem. 26 (2011) 1093-1102. DOI: 10.1159/000323987.CrossrefWeb of ScienceGoogle Scholar

  • 24. Galea, G.L., Meakin, L.B., Sugiyama, T., Zebda, N., Sunters, A., Taipaleenmaki, H., Stein, G.S., van Wijnen, A.J., Lanyon, L.E. and Price, J.S. Estrogen receptor α mediates proliferation of osteoblastic cells stimulated by estrogen and mechanical strain, but their acute downregulation of the Wnt antagonist Sost is mediated by estrogen receptor β. J. Biol. Chem. 288 (2013) 9035-9048. DOI: 10.1074/jbc.M112.405456.CrossrefWeb of ScienceGoogle Scholar

  • 25. Tang, J., Ahmad, A. and Sarkar, F.H. The role of microRNAs in breast cancer migration, invasion and metastasis. Int. J. Mol. Sci. 13 (2012) 13414-13437. DOI: 10.3390/ijms131013414.CrossrefGoogle Scholar

  • 26. Jorganes, A.C., Araldi, E., Penalva, L.F., Sandhu, D., Hernando, C.F. and Suárez,Y. MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in endothelial cells via targeting vascular endothelial growth factor receptor-2 and fibroblast growth factor receptor-1. Arterioscler. Throm. Vasc. Biol. 31 (2011) 2595-2606. DOI: 10.1161/ATVBAHA.111.236521.Web of ScienceGoogle Scholar

  • 27. Yang, J., Qin, S., Yi, C., Ma, G., Zhu, H., Zhou, W., Xiong, Y., Zhu, X., Wang, Y., He, L. and Guo, X. MiR-140 is co-expressed with< i> Wwp2- C</i> transcript and activated by Sox9 to target< i> Sp1</i> in maintaining the chondrocyte proliferation. FEBS Lett. 585 (2011) 2992-2997. DOI: 10.1016/j.febslet.2011.08.013.Web of ScienceCrossrefGoogle Scholar

  • 28. Lin, G. and Hankenson, K.D. Integration of BMP, Wnt, and notch signaling pathways in osteoblast differentiation. J. Cell Biochem. 11 (2011) 3491-3501. DOI: 10.1002/jcb.23287.Web of ScienceCrossrefGoogle Scholar

  • 29. Ng, C.F., Xu, J., Li, M.S. and Tsui, S.K. Identification of FHL2-Regulated Genes in Liver by Microarray and Bioinformatics Analysis. J. Cell Biochem. 115 (2014) 744-753. DOI: 10.1002/jcb.24714.Web of ScienceCrossrefGoogle Scholar

  • 30. Wang, S., Huang, H., Chen, S., Li, X., Zhang, W. and Tang, Q. Gdf6 induces commitment of pluripotent mesenchymal C3H10T1/2 cells to the adipocyte lineage. FEBS J. 280 (2013) 2644-2651. DOI: 10.1111/ febs.12256.Web of ScienceCrossrefGoogle Scholar

  • 31. Gradus, B. and Hornstein, E. Role of microRNA in skeleton development. Bone and Development 6 (2010) 81-91. DOI: 10.1007/978-1-84882-822-3_5.Web of ScienceCrossrefGoogle Scholar

  • 32. Roson-Burgo, B., Sanchez-Guijo, F., Cañizo, C.D. and Las Rivas, J.D. Transcriptomic portrait of human mesenchymal stromal/stem cells isolated from bone marrow and placenta. BMC Genomics 15 (2014) 910-910. DOI: 10.1186/1471-2164-15-910.Web of ScienceCrossrefGoogle Scholar

  • 33. Ishibashi, O. and Inui, T. Identification of endoglin-dependent BMP-2- induced genes in the murine periodontal ligament cell line PDL-L2. J. Mol. Signal. 9 (2014) 5. DOI: 10.1186/1750-2187-9-5. CrossrefGoogle Scholar

About the article

Received: 2014-12-31

Accepted: 2015-06-28

Published Online: 2015-10-15

Published in Print: 2015-12-01

Citation Information: Cellular and Molecular Biology Letters, Volume 20, Issue 4, Pages 586–596, ISSN (Online) 1689-1392, DOI: https://doi.org/10.1515/cmble-2015-0034.

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