Browse > Article

Bone Morphogenetic Protein 2-induced MAPKs Activation Is Independent of the Smad1/5 Activation  

Jun, Ji-Hae (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University)
Ryoo, Hyun-Mo (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University)
Woo, Kyung-Mi (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University)
Kim, Gwan-Shik (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University)
Baek, Jeong-Hwa (Department of Cell & Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University)
Publication Information
International Journal of Oral Biology / v.34, no.2, 2009 , pp. 115-121 More about this Journal
Abstract
Bone morphogenetic protein (BMP) 2 is a potent osteogenic factor. Although both Smad1/5 and mitogenactivated protein kinases (MAPKs) are activated by BMP2, the hierarchical relationship between them is unclear. In this study, we examined if BMP2-stimulated MAPK activation is regulated by Smad1/5 or vice versa. When C2C12 cells were treated with BMP2, the activation of extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun-N-terminal kinase was evident within 5 min. The knockdown of both Smad1 and Smad5 by small interfering RNA did not affect the activation of these MAPKs. In addition, neither the overexpression of Smad1 nor Smad5 induced ERK activation. When ERK activation was induced by constitutively active MEK1 expression, the protein level and activation of Smad1 increased. Furthermore, the inhibition of constitutively active BMP receptor type IB-induced ERK activation significantly suppressed Smad1 activation. These results indicate that Smad1/5 activation is not necessary for BMP2-induced MAPK activation and also that ERK positively regulates Smad1 activation.
Keywords
Bone morphogenetic protein 2; Smad1; Smad5; Mitogen-activated protein kinase (MAPK);
Citations & Related Records
연도 인용수 순위
  • Reference
1 Higuchi C, Myoui A, Hashimoto N, Kuriyama K, Yoshioka K, Yoshikawa H, Itoh K. Continuous inhibition of MAPK signaling promotes the early osteoblastic differentiation and mineralization of the extracellular matrix. J Bone Miner Res. 2002;17:1785-94   DOI   ScienceOn
2 Ryoo HM, Lee MH, Kim YJ. Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene. 2006;366:51-7   DOI   ScienceOn
3 Ungefroren H, Lenschow W, Chen WB, Faendrich F, Kalthoff H. Regulation of biglycan gene expression by transforming growth factor-beta requires MKK6-p38 mitogen-activated protein Kinase signaling downstream of Smad signaling. J Biol Chem. 2003;278:11041-9   DOI   ScienceOn
4 Yamaguchi K, Nagai S, Ninomiya-Tsuji J, Nishita M, Tamai K, Irie K, Ueno N, Nishida E, Shibuya H, Matsumoto K. XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway. EMBO J. 1999;18:179-87   DOI   ScienceOn
5 Sapkota G, Alarc$\acute{o}$n C, Spagnoli FM, Brivanlou AH, Massagu$\acute{e}$ J. Balancing BMP signaling through integrated inputs into the Smad1 linker. Mol Cell. 2007;25:441-54   DOI   ScienceOn
6 Miyazono K, Maeda S, Imamura T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 2005;16:251-63   DOI   ScienceOn
7 Kozawa O, Hatakeyama D, Uematsu T. Divergent regulation by p44/p42 MAP kinase and p38 MAP kinase of bone morphogenetic protein-4-stimulated osteocalcin synthesis in osteoblasts. J Cell Biochem. 2002;84:583-9   DOI   ScienceOn
8 Takekawa M, Tatebayashi K, Itoh F, Adachi M, Imai K, Saito H. Smad-dependent GADD45beta expression mediates delayed activation of p38 MAP kinase by TGF-beta. EMBO J. 2002;21:6473-82   DOI
9 Moustakas A, Heldin CH. Non-Smad TGF-beta signals. J Cell Sci. 2005;118:3573-84   DOI   ScienceOn
10 Fujii M, Takeda K, Imamura T, Aoki H, Sampath TK, Enomoto S, Kawabata M, Kato M, Ichijo H, Miyazono K. Roles of bone morphogenetic protein type I receptors and Smad proteins in osteoblast and chondroblast differentiation. Mol Biol Cell. 1999;10:3801-13   DOI   PUBMED   ScienceOn
11 Noth U, Tuli R, Seghatoleslami R, Howard M, Shah A, Hall DJ, Hickok NJ, Tuan RS. Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts. Exp Cell Res. 2003;291:201-11   DOI   ScienceOn
12 Suzawa M, Tamura Y, Fukumoto S, Miyazono K, Fujita T, Kato S, Takeuchi Y. Stimulation of Smad1 transcriptional activity by Ras-extracellular signal-regulated kinase pathway: a possible mechanism for collagen-dependent osteoblastic differentiation. J Bone Miner Res. 2002;17:240-8   DOI   ScienceOn
13 Hassel S, Schmitt S, Hartung A, Roth M, Nohe A, Petersen N, Ehrlich M, Henis YI, Sebald W, Knaus P. Initiation of Smaddependent and Smad-independent signaling via distinct BMP-receptor complexes. J Bone Joint Surg Am. 2003;85-A Suppl 3:44-51
14 Lee KS, Kim HJ, Li QL, Chi XZ, Ueta C, Komori T, Wozney JM, Kim EG, Choi JY, Ryoo HM, Bae SC. Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol Cell Biol. 2000;20:8783-92   DOI   ScienceOn
15 Guicheux J, Lemonnier J, Ghayor C, Suzuki A, Palmer G, Caverzasio J. Activation of p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation. J Bone Miner Res. 2003;18:2060-8   DOI   ScienceOn
16 Jordan BW, Dinev D, LeMellay V, Troppmair J, Gotz R, Wixler L, Sendtner M, Ludwig S, Rapp UR. Neurotrophin receptor-interacting mage homologue is an inducible inhibitor of apoptosis protein-interacting protein that augments cell death. J Biol Chem. 2001;276:39985-9   DOI   ScienceOn
17 Nohe A, Hassel S, Ehrlich M, Neubauer F, Sebald W, Henis YI, Knaus P. The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways. J Biol Chem. 2002;277:5330-8   DOI   ScienceOn
18 Shirakabe K, Yamaguchi K, Shibuya H, Irie K, Matsuda S, Moriguchi T, Gotoh Y, Matsumoto K, Nishida E. TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase. J Biol Chem. 1997;272:8141-4   DOI   ScienceOn
19 Gallea S, Lallemand F, Atfi A, Rawadi G, Ramez V, Spinella-Jaegle S, Kawai S, Faucheu C, Huet L, Baron R, Roman-Roman S. Activation of mitogen-activated protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2C12 cells. Bone. 2001;28:491-8   DOI   ScienceOn
20 Osyczka AM, Leboy PS. Bone morphogenetic protein regulation of early osteoblast genes in human marrow stromal cells is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. Endocrinology. 2005;146:3428-37   DOI   ScienceOn
21 Yamamoto N, Akiyama S, Katagiri T, Namiki M, Kurokawa T, Suda T. Smad1 and smad5 act downstream of intracellular signalings of BMP-2 that inhibits myogenic differentiation and induces osteoblast differentiation in C2C12 myoblasts. Biochem Biophys Res Commun. 1997;238:574-80   DOI   ScienceOn
22 Kretzschmar M, Doody J, MassaguJ. Opposing BMP and EGF signalling pathways converge on the TGF-beta family mediator Smad1. Nature. 1997;389:618-22   DOI   PUBMED   ScienceOn