Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board: Buchner, Johannes / Lei, Ming / Ludwig, Stephan / Sies, Helmut / Thomas, Douglas D. / Turk, Boris / Wittinghofer, Alfred


IMPACT FACTOR 2017: 3.022

CiteScore 2017: 2.81

SCImago Journal Rank (SJR) 2017: 1.562
Source Normalized Impact per Paper (SNIP) 2017: 0.705

Online
ISSN
1437-4315
See all formats and pricing
More options …
Volume 396, Issue 4

Issues

microRNA-210 is involved in the regulation of postmenopausal osteoporosis through promotion of VEGF expression and osteoblast differentiation

Xiao-Dong Liu
  • Corresponding author
  • Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, #450 Tengyue Road, Shanghai 200090, China
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Feng Cai
  • Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, #1239 Siping Road, Shanghai 200090, China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Liang Liu
  • Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, #1239 Siping Road, Shanghai 200090, China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Yan Zhang
  • Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, #1239 Siping Road, Shanghai 200090, China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ An-Li Yang
  • Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, #1239 Siping Road, Shanghai 200090, China
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2015-01-15 | DOI: https://doi.org/10.1515/hsz-2014-0268

Abstract

MicroRNAs (miRNAs) are small non-protein-codingRNAs that function as negative gene expression regulators. miRNA-210 (miR-210) has recently been recognized in the pathogenesis of osteonecrosis associated with angiogenesis. Herein we aimed to explore the clinical significance of miR-210 treatment for postmenopausal osteoporosis. The expression of miR-210 was detected in bone marrow mesenchymal stem cells (BMSCs) in vitro and miR-210 significantly promoted the expression of vascular edothelial growth factor (VEGF) in BMSCs in a time-dependent manner (p<0.05). And miR-210 suppressed PPARγ expression but increased the expression of ALP and osterix, demonstrating that miR-210 inhibited adipocyte differentiation and promoted osteoblast differentiation of BMSCs in vitro. The protein expression of hypoxia-inducible factor 1 alpha (HIF-1α) and VEGF in 17β-estradiol (E2) treated osteoblasts were significantly increased in a dose- and time-dependent manner (p<0.05). And E2 inducted the VEGF expression through the PI3K/AKT signaling pathway in osteoblasts. Taken together, these data implied that miR-210 played an important role in ameliorating the estrogen deficiency caused-postmenopausal osteoporosis through promotion the VEGF expression and osteoblast differentiation.

Keywords: BMSC differentiation; miR-210; postmenopausal osteoporosis; VEGF

References

  • Ambros, V. (2004). The functions of animal microRNAs. Nature 431, 350–355.Google Scholar

  • Bartel, D.P. (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116, 281–297.Web of ScienceGoogle Scholar

  • Bonnick, S.L., Harris, S.T., Kendler, D.L., McClung, M.R., and Silverman, S.L. (2010). Management of osteoporosis in postmenopausal women: 2010 position statement of the North American Menopause Society. Menopause 17, 25–54; quiz 55–26.Google Scholar

  • Burkhardt, R., Kettner, G., Böhm, W., Schmidmeier, M., Schlag, R., Frisch, B., Mallmann, B., Eisenmenger, W., and Gilg, T. (1987). Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study. Bone 8, 157–164.CrossrefPubMedGoogle Scholar

  • Camps, C., Buffa, F.M., Colella, S., Moore, J., Sotiriou, C., Sheldon, H., Harris, A.L., Gleadle, J.M., and Ragoussis, J. (2008). Hsa-miR-210 is induced by hypoxia and is an independent prognostic factor in breast cancer. Clin. Cancer Res. 14, 1340–1348.Google Scholar

  • Corina, M., Vulpoi, C., and Branisteanu, D. (2012). Relationship between bone mineral density, weight, and estrogen levels in pre and postmenopausal women. Rev. Med. Chir. Soc. Med. Nat. Iasi. 116, 946–950.Google Scholar

  • Crosby, M.E., Kulshreshtha, R., Ivan, M., and Glazer, P.M. (2009). MicroRNA regulation of DNA repair gene expression in hypoxic stress. Cancer Res. 69, 1221–1229.Google Scholar

  • Ding, W.G., Wei, Z.X., and Liu, J.B. (2011). Reduced local blood supply to the tibial metaphysis is associated with ovariectomy-induced osteoporosis in mice. Connect. Tissue Res. 52, 25–29.Web of ScienceCrossrefPubMedGoogle Scholar

  • Ell, B., Mercatali, L., Ibrahim, T., Campbell, N., Schwarzenbach, H., Pantel, K., Amadori, D., and Kang, Y. (2013). Tumor-induced osteoclast miRNA changes as regulators and biomarkers of osteolytic bone metastasis. Cancer Cell 24, 542–556.PubMedWeb of ScienceCrossrefGoogle Scholar

  • Erwin, G.S., Crisostomo, P.R., Wang, Y., Wang, M., Markel, T.A., Guzman, M., Sando, L.C., Sharma, R., and Meldrum, D.R. (2009). Estradiol-treated mesenchymal stem cells improve myocardial recovery after ischemia. J. Surg. Res. 152, 319–324.Web of ScienceGoogle Scholar

  • Ettinger, B., Genant, H.K., and Cann, C.E. (1985). Long-term estrogen replacement therapy prevents bone loss and fractures. Ann. Intern. Med. 102, 319–324.Google Scholar

  • Farh, K.K., Grimson, A., Jan, C., Lewis, B.P., Johnston, W.K., Lim, L.P., Burge, C.B., and Bartel, D.P. (2005). The widespread impact of mammalian MicroRNAs on mRNA repression and evolution. Science 310, 1817–1821.Google Scholar

  • Fasanaro, P., D’Alessandra, Y., Di Stefano, V., Melchionna, R., Romani, S., Pompilio, G., Capogrossi, M.C., and Martelli, F. (2008). MicroRNA-210 modulates endothelial cell response to hypoxia and inhibits the receptor tyrosine kinase ligand Ephrin-A3. J. Biol. Chem. 283, 15878–15883.Web of ScienceGoogle Scholar

  • Fish, J.E., Santoro, M.M., Morton, S.U., Yu, S., Yeh, R.F., Wythe, J.D., Ivey, K.N., Bruneau, B.G., Stainier, D.Y., and Srivastava, D. (2008). miR-126 regulates angiogenic signaling and vascular integrity. Dev. Cell 15, 272–284.PubMedCrossrefGoogle Scholar

  • Foekens, J.A., Sieuwerts, A.M., Smid, M., Look, M.P., de Weerd, V., Boersma, A.W., Klijn, J.G., Wiemer, E.A., and Martens, J.W. (2008). Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc. Natl. Acad. Sci. USA 105, 13021–13026.Web of ScienceGoogle Scholar

  • Garnero, P. (2014). New developments in biological markers of bone metabolism in osteoporosis. Bone 66, 46–55.Web of SciencePubMedCrossrefGoogle Scholar

  • Hamrick, M.W., Herberg, S., Arounleut, P., He, H.Z., Shiver, A., Qi, R.Q., Zhou, L., Isales, C.M., and Mi, Q.S. (2010). The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice. Biochem. Biophys. Res. Commun. 400, 379–383.Web of ScienceGoogle Scholar

  • Hu, Y.C., Cheng, H.L., Hsieh, B.S., Huang, L.W., Huang, T.C., and Chang, K.L. (2012). Arsenic trioxide affects bone remodeling by effects on osteoblast differentiation and function. Bone 50, 1406–1415.Web of ScienceGoogle Scholar

  • Huang, X., Ding, L., Bennewith, K.L., Tong, R.T., Welford, S.M., Ang, K.K., Story, M., Le, Q.T., and Giaccia, A.J. (2009). Hypoxia-inducible mir-210 regulates normoxic gene expression involved in tumor initiation. Mol. Cell 35, 856–867.Google Scholar

  • Johnston, C.C. Jr., Hui, S.L., Witt, R.M., Appledorn, R., Baker, R.S., and Longcope, C. (1985). Early menopausal changes in bone mass and sex steroids. J. Clin. Endocrinol. Metab. 61, 905–911.Google Scholar

  • Kanis, J.A. (1994). Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos. Int. 4, 368–381.CrossrefGoogle Scholar

  • Krützfeldt, J., Rajewsky, N., Braich, R., Rajeev, K.G., Tuschl, T., Manoharan, M., and Stoffel, M. (2005). Silencing of microRNAs in vivo with ‘antagomirs’. Nature 438, 685–689.Google Scholar

  • Lee, R.C., Feinbaum, R.L., Ambros, V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75, 843–854.Google Scholar

  • Ma, L., Reinhardt, F., Pan, E., Soutschek, J., Bhat, B., Marcusson, E.G., Teruya-Feldstein, J., Bell, G.W., Weinberg, R.A. (2010). Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat. Biotechnol. 284, 341–347.Web of ScienceGoogle Scholar

  • Maeda, S.S., and Lazaretti-Castro, M. (2014). An overview on the treatment of postmenopausal osteoporosis. Arq. Bras. Endocrinol. Metabol. 58, 162–171.Web of ScienceGoogle Scholar

  • Maire, G., Martin, J.W., Yoshimoto, M., Chilton-MacNeill, S., Zielenska, M., Squire, J.A. (2011). Analysis of miRNA-gene expression-genomic profiles reveals complex mechanisms of microRNA deregulation in osteosarcoma. Cancer Genet. 204, 138–146.Web of ScienceGoogle Scholar

  • Makins, R., and Ballinger, A. (2003). Gastrointestinal side effects of drugs. Expert Opin. Drug. Saf. 2, 421–429.CrossrefGoogle Scholar

  • Manolagas, S.C. (2000). Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr. Rev. 21, 115–137.PubMedGoogle Scholar

  • Mizuno, Y., Tokuzawa, Y., Ninomiya, Y., Yagi, K., Yatsuka-Kanesaki, Y., Suda, T., Fukuda, T., Katagiri, T., Kondoh, Y., Amemiya, T., Tashiro, H., Okazaki, Y. (2009). miR-210 promotes osteoblastic differentiation through inhibition of AcvR1b. FEBS Lett. 583, 2263–2268.Web of ScienceGoogle Scholar

  • Nakasa, T., Ishikawa, M., Shi, M., Shibuya, H., Adachi, N., Ochi, M. (2010). Acceleration of muscle regeneration by local injection of muscle-specific microRNAs in rat skeletal muscle injury model. J. Cell. Mol. Med. 14, 2495–2505.CrossrefWeb of ScienceGoogle Scholar

  • Nilas, L. and Christiansen, C. (1987). Bone mass and its relationship to age and the menopause. J. Clin. Endocrinol. Metab. 65, 697–702.Google Scholar

  • Ohta, H., Makita, K., Suda, Y., Ikeda, T., Masuzawa, T., Nozawa, S. (1992). Influence of oophorectomy on serum levels of sex steroids and bone metabolism and assessment of bone mineral density in lumbar trabecular bone by QCT-C value. J. Bone Miner. Res. 7, 659–665.Google Scholar

  • Riggs, B.L., Khosla, S., Melton, L.J. (2002). Sex steroids and the construction and conservation of the adult skeleton. Endocr. Rev. 23, 279–302.CrossrefPubMedGoogle Scholar

  • Rubin, M.R., and Bilezikian, J.P. (2003). The anabolic effects of parathyroid hormone therapy. Clin. Geriatr. Med. 19, 415–432.CrossrefPubMedGoogle Scholar

  • Simon, J.A. (2012). What’s new in hormone replacement therapy: focus on transdermal estradiol and micronized progesterone. Climacteric 15, 3–10.Web of ScienceCrossrefGoogle Scholar

  • Street, J., Bao, M., deGuzman, L., Bunting, S., Peale, F.V. Jr., Ferrara, N., Steinmetz, H., Hoeffel, J., Cleland, J.L., Daugherty, A., et al. (2002). Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc. Natl. Acad. Sci. USA 99, 9656–9661.Google Scholar

  • Syed, F. and Khosla, S. (2005). Mechanisms of sex steroid effects on bone. Biochem. Biophys. Res. Commun. 328, 688–696.Google Scholar

  • Takeshita, F., Patrawala, L., Osaki, M., Takahashi, R.U., Yamamoto, Y., Kosaka, N., Kawamata, M., Kelnar, K., Bader, A.G., Brown, D., et al. (2010). Systemic delivery of synthetic microRNA-16 inhibits the growth of metastatic prostate tumors via downregulation of multiple cell-cycle genes. Mol. Ther. 18, 181–187.CrossrefPubMedWeb of ScienceGoogle Scholar

  • Tazawa, H., Tsuchiya, N., Izumiya, M., and Nakagama, H. (2007). Tumor-suppressive miR-34a induces senescence-like growth arrest through modulation of the E2F pathway in human colon cancer cells. Proc. Natl. Acad. Sci. USA 104, 15472–15477.Web of ScienceGoogle Scholar

  • Tornero-Esteban, P., Hoyas, J.A., Villafuertes, E., Garcia-Bullón, I., Moro, E., Fernández-Gutiérrez, B., and Marco, F. (2014). Study of the role of miRNA in mesenchymal stem cells isolated from osteoarthritis patients. Rev. Esp. Cir. Ortop. Traumatol. 58, 138–143.Google Scholar

  • Turner, R.T., Riggs, B.L., and Spelsberg, T.C. (1994). Skeletal effects of estrogen. Endocr. Rev. 15, 275–300.PubMedGoogle Scholar

  • Tyagi, A.M., Srivastava, K., Mansoori, M.N., Trivedi, R., Chattopadhyay, N., and Singh, D. (2012). Estrogen deficiency induces the differentiation of IL-17 secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis. PLoS One 7, e44552.Google Scholar

  • Wahid, F., Shehzad, A., Khan, T., and Kim, Y.Y. (2010) MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim. Biophys. Acta 1803, 1231–1243.Web of ScienceGoogle Scholar

  • Wang, Y., Wan, C., Deng, L., Liu, X., Cao, X., Gilbert, S.R., Bouxsein, M.L., Faugere, M.C., Guldberg, R.E., Gerstenfeld, L.C., et al. (2007). The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J. Clin. Invest. 117, 1616–1626.Web of ScienceGoogle Scholar

  • Wang, S., Aurora, A.B., Johnson, B.A., Qi, X., McAnally, J., Hill, J.A., Richardson, J.A., Bassel-Duby, R., and Olson, E.N. (2008). The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev. Cell 15, 261–271.PubMedCrossrefGoogle Scholar

  • Weitzmann, M.N. and Pacifici, R. (2005). The role of T lymphocytes in bone metabolism. Immunol. Rev. 208, 154–168.Google Scholar

  • Wronski, T.J., Dann, L.M., Scott, K.S., and Cintrón, M. (1989). Long-term effects of ovariectomy and aging on the rat skeleton. Calcif. Tissue Int. 45, 360–366.Google Scholar

  • Yang, B., Lin, H., Xiao, J., Lu, Y., Luo, X., Li, B., Zhang, Y., Xu, C., Bai, Y., Wang, H., et al. (2007). The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2. Nat. Med. 13, 486–491.Web of ScienceCrossrefGoogle Scholar

  • Yamasaki, K., Nakasa, T., Miyaki, S., Yamasaki, T., Yasunaga, Y., and Ochi, M. (2012). Angiogenic microRNA-210 is present in cells surrounding osteonecrosis. J. Orthop. Res. 30, 1263–1270.Google Scholar

  • Zhang, Z., Sun, H., Dai, H., Walsh, R.M., Imakura, M., Schelter, J., Burchard, J., Dai, X., Chang, A.N., Diaz, R.L., et al. (2009). MicroRNA miR-210 modulates cellular response to hypoxia through the MYC antagonist MNT. Cell Cycle 8, 2756–2768.Web of ScienceGoogle Scholar

About the article

Corresponding author: Xiao-Dong Liu, Department of Orthopedics, YangPu Hospital, TongJi University School of Medicine, #450 Tengyue Road, Shanghai 200090, China, e-mail:

aThese authors contributed equally to this work.


Received: 2014-11-03

Accepted: 2014-12-05

Published Online: 2015-01-15

Published in Print: 2015-04-01


Citation Information: Biological Chemistry, Volume 396, Issue 4, Pages 339–347, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: https://doi.org/10.1515/hsz-2014-0268.

Export Citation

©2015 by De Gruyter.Get Permission

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Zhi-hao Wu, Kai-hua Huang, Kang Liu, Guan-tong Wang, and Qiang Sun
Biochemical and Biophysical Research Communications, 2018
[2]
Wenhua Zhao, Gengyang Shen, Hui Ren, De Liang, Xiang Yu, Zhida Zhang, Jinjing Huang, Ting Qiu, Jingjing Tang, Qi Shang, Peiyuan Yu, Zixian Wu, and Xiaobing Jiang
Journal of Cellular Physiology, 2018
[3]
Lin Li, Shaoqing Yang, Yanli Zhang, Dongrui Ji, Zuolin Jin, and Xiaohong Duan
Biochemical and Biophysical Research Communications, 2018
[4]
Chi-Chih Chang, Morten T. Venø, Li Chen, Nicholas Ditzel, Dang Q.S. Le, Philipp Dillschneider, Moustapha Kassem, and Jørgen Kjems
Molecular Therapy, 2017
[7]
Yunhe Xu, Jiayuan Shen, Fenik Kaml Muhammed, Bowen Zheng, Yuejiao Zhang, and Yi Liu
Cell Biochemistry and Function, 2017
[8]
Han Wang, Zhongyang Sun, Yixuan Wang, Zebing Hu, Hua Zhou, Lianchang Zhang, Bo Hong, Shu Zhang, and Xinsheng Cao
Scientific Reports, 2016, Volume 6, Number 1
[9]
Heng-feng Yuan, Von Roemeling Christina, Chang-an Guo, Yi-wei Chu, Rong-hua Liu, and Zuo-qin Yan
Scientific Reports, 2016, Volume 6, Number 1
[10]
Dorothea Portius, Cyril Sobolewski, and Michelangelo Foti
PPAR Research, 2017, Volume 2017, Page 1
[11]
Haixia Zhang, Qing Mai, and Juntao Chen
Cell Biology International, 2017, Volume 41, Number 3, Page 267
[12]
Qiang Li, Rui Liu, Jianmin Zhao, and Quanli Lu
The Journal of Toxicological Sciences, 2016, Volume 41, Number 5, Page 701
[13]
Chuan Wang, Haiqing Liao, and Zhengguo Cao
Medical Science Monitor, 2016, Volume 22, Page 2934
[14]
Mengge Sun, Xiaoya Zhou, Lili Chen, Shishu Huang, Victor Leung, Nan Wu, Haobo Pan, Wanxin Zhen, William Lu, and Songlin Peng
BioMed Research International, 2016, Volume 2016, Page 1

Comments (0)

Please log in or register to comment.
Log in