Potential Mechanisms Underlying the Runx2 Induced Osteogenesis of Bone Marrow Mesenchymal Stem Cells

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2016 Feb 18

PMID 26885254

Citations 95

Authors

Jiahai Xu

Zhanghua Li

Yudong Hou

Weijun Fang

Affiliations

Soon will be listed here.

Abstract

Bone marrow derived mesenchymal stem cells (BM-MSCs) belong a type of pluripotent stem cells and can be induced to differentiate into osteoblasts (OB). Runt-related transcription factor 2 (Runx2) is an osteogenesis specific transcription factor and plays an important role in osteogenesis of BM-MSCs. It can promote the expression of osteogenesis related genes, regulate cell cycle progression, improve bone microenvironment and affect functions of chondrocytes and osteoclasts, which have involvement of a large amount of signal molecules including TGF-β, BMP, Notch, Wnt, Hedgehog, FGF and microRNA. In this paper, we summarize the mechanisms underlying the Runx2 induced osteogenesis of BM-MSCs.

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References

Lee K, Hong S, Bae S . Both the Smad and p38 MAPK pathways play a crucial role in Runx2 expression following induction by transforming growth factor-beta and bone morphogenetic protein. Oncogene. 2002; 21(47):7156-63. DOI: 10.1038/sj.onc.1205937. View

Hill C, Yuasa M, Schoenecker J, Goudy S . Jagged1 is essential for osteoblast development during maxillary ossification. Bone. 2014; 62:10-21. PMC: 4306467. DOI: 10.1016/j.bone.2014.01.019. View

Chen G, Deng C, Li Y . TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci. 2012; 8(2):272-88. PMC: 3269610. DOI: 10.7150/ijbs.2929. View

Kook S, Heo J, Lee J . Crucial roles of canonical Runx2-dependent pathway on Wnt1-induced osteoblastic differentiation of human periodontal ligament fibroblasts. Mol Cell Biochem. 2015; 402(1-2):213-23. DOI: 10.1007/s11010-015-2329-y. View

Zheng H, Guo Z, Ma Q, Jia H, Dang G . Cbfa1/osf2 transduced bone marrow stromal cells facilitate bone formation in vitro and in vivo. Calcif Tissue Int. 2003; 74(2):194-203. DOI: 10.1007/s00223-003-0004-x. View

Zelzer E, Glotzer D, Hartmann C, Thomas D, Fukai N, Soker S . Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2. Mech Dev. 2001; 106(1-2):97-106. DOI: 10.1016/s0925-4773(01)00428-2. View

Huang J, Zhao L, Xing L, Chen D . MicroRNA-204 regulates Runx2 protein expression and mesenchymal progenitor cell differentiation. Stem Cells. 2009; 28(2):357-64. PMC: 2837600. DOI: 10.1002/stem.288. View

Liu W, Toyosawa S, Furuichi T, Kanatani N, Yoshida C, Liu Y . Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J Cell Biol. 2001; 155(1):157-66. PMC: 2150799. DOI: 10.1083/jcb.200105052. View

Hassan M, Gordon J, Beloti M, Croce C, van Wijnen A, Stein J . A network connecting Runx2, SATB2, and the miR-23a~27a~24-2 cluster regulates the osteoblast differentiation program. Proc Natl Acad Sci U S A. 2010; 107(46):19879-84. PMC: 2993380. DOI: 10.1073/pnas.1007698107. View

10.

Kang H, Hata A . The role of microRNAs in cell fate determination of mesenchymal stem cells: balancing adipogenesis and osteogenesis. BMB Rep. 2014; 48(6):319-23. PMC: 4578617. DOI: 10.5483/bmbrep.2015.48.6.206. View

11.

Hilton M, Tu X, Wu X, Bai S, Zhao H, Kobayashi T . Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med. 2008; 14(3):306-14. PMC: 2740725. DOI: 10.1038/nm1716. View

12.

Caplan A . Why are MSCs therapeutic? New data: new insight. J Pathol. 2008; 217(2):318-24. PMC: 8793150. DOI: 10.1002/path.2469. View

13.

Yu S, Geng Q, Ma J, Sun F, Yu Y, Pan Q . Heparin-binding EGF-like growth factor and miR-1192 exert opposite effect on Runx2-induced osteogenic differentiation. Cell Death Dis. 2013; 4:e868. PMC: 3824672. DOI: 10.1038/cddis.2013.363. View

14.

Zhang Y, Xie R, Gordon J, LeBlanc K, Stein J, Lian J . Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2. J Biol Chem. 2012; 287(26):21926-35. PMC: 3381153. DOI: 10.1074/jbc.M112.340398. View

15.

Lee M, Javed A, Kim H, Shin H, Gutierrez S, Choi J . Transient upregulation of CBFA1 in response to bone morphogenetic protein-2 and transforming growth factor beta1 in C2C12 myogenic cells coincides with suppression of the myogenic phenotype but is not sufficient for osteoblast differentiation. J Cell Biochem. 1999; 73(1):114-25. View

16.

Larabee J, Shakir S, Barua S, Ballard J . Increased cAMP in monocytes augments Notch signaling mechanisms by elevating RBP-J and transducin-like enhancer of Split (TLE). J Biol Chem. 2013; 288(30):21526-36. PMC: 3724613. DOI: 10.1074/jbc.M113.465120. View

17.

Hu N, Feng C, Jiang Y, Miao Q, Liu H . Regulative Effect of Mir-205 on Osteogenic Differentiation of Bone Mesenchymal Stem Cells (BMSCs): Possible Role of SATB2/Runx2 and ERK/MAPK Pathway. Int J Mol Sci. 2015; 16(5):10491-506. PMC: 4463658. DOI: 10.3390/ijms160510491. View

18.

Sakamoto K, Tamamura Y, Katsube K, Yamaguchi A . Zfp64 participates in Notch signaling and regulates differentiation in mesenchymal cells. J Cell Sci. 2008; 121(Pt 10):1613-23. DOI: 10.1242/jcs.023119. View

19.

Watanabe K, Ikeda K . [Osteoblast differentiation and bone formation]. Nihon Rinsho. 2009; 67(5):879-86. View

20.

Mendoza-Villanueva D, Zeef L, Shore P . Metastatic breast cancer cells inhibit osteoblast differentiation through the Runx2/CBFβ-dependent expression of the Wnt antagonist, sclerostin. Breast Cancer Res. 2011; 13(5):R106. PMC: 3262219. DOI: 10.1186/bcr3048. View