This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Harada, S.-i. Articles by Rodan, G. A. Search for Related Content PubMed PubMed Citation Articles by Harada, S.-i. Articles by Rodan, G. A.

Osteogenic Protein-1 Up-Regulation of the Collagen X Promoter Activity Is Mediated by a MEF-2-Like Sequence and Requires an Adjacent AP-1 Sequence

Department of Bone Biology and Osteoporosis Research (S.H., G.A.R.) Merck Research Laboratories, West Point, Pennsylvania 19486
Creative Biomolecules, Inc. (T.K.S.) Hopkinton, Massachusetts 01748
Department of Anatomy and Cell Biology (J.E.A.) Faculty of Medicine University of Toronto Toronto, Ontario M5S 1A8, Canada

Bone morphogenetic proteins induce chondrogenesis and osteogenesis in vivo. To investigate molecular mechanisms involved in chondrocyte induction, we examined the effect of osteogenic protein (OP)-1/bone morphogenetic protein-7 on the collagen X promoter. In rat calvaria-derived chondrogenic C5.18 cells, OP-1 up-regulates collagen X mRNA levels and its promoter activity in a cell type- specific manner. Deletion analysis localizes the OP-1 response region to 33 bp (-310/-278), which confers OP-1 responsiveness to both the minimal homologous and heterologous Rous sarcoma virus promoter. Transforming growth factor-ß2 or activin, which up-regulates the expression of a transforming growth factor-ß-inducible p3TP-Lux construct, has little effect on collagen X mRNA and on this 33-bp region. Mutational analysis shows that both an AP-1 like sequence (-294/-285, TGAATCATCA) and an A/T-rich myocyte enhancer factor (MEF)-2 like sequence (-310/-298, TTAAAAATAAAAA) in the 33-bp region are necessary for the OP-1 effect. Gel shift assays show interaction of distinct nuclear proteins from C5.18 cells with the AP-1-like and the MEF-2- like sequences. OP-1 rapidly induces nuclear protein interaction with the MEF-2-like sequence but not with the AP-1 like sequence. MEF-2-like binding activity induced by OP-1 is distinct from the MEF-2 family proteins present in C2C12 myoblasts, in which OP-1 does not induce collagen X mRNA or up-regulate its promoter activity. In conclusion, we identified a specific response region for OP-1 in the mouse collagen X promoter. Mutational and gel shift analyses suggest that OP-1 induces nuclear protein interaction with an A/T-rich MEF-2 like sequence, distinct from the MEF-2 present in myoblasts, and up-regulates collagen X promoter activity, which also requires an AP-1 like sequence.

This article has been cited by other articles:

				E. Bonnelye, R. A. Zirngibl, P. Jurdic, and J. E. Aubin The Orphan Nuclear Estrogen Receptor-Related Receptor-{alpha} Regulates Cartilage Formation in Vitro: Implication of Sox9 Endocrinology, March 1, 2007; 148(3): 1195 - 1205. [Abstract] [Full Text] [PDF]

				C. Magee, M. Nurminskaya, L. Faverman, P. Galera, and T. F. Linsenmayer SP3/SP1 Transcription Activity Regulates Specific Expression of Collagen Type X in Hypertrophic Chondrocytes J. Biol. Chem., July 8, 2005; 280(27): 25331 - 25338. [Abstract] [Full Text] [PDF]

				F. Karreth, A. Hoebertz, H. Scheuch, R. Eferl, and E. F. Wagner The AP1 transcription factor Fra2 is required for efficient cartilage development Development, November 15, 2004; 131(22): 5717 - 5725. [Abstract] [Full Text] [PDF]

				S. Hannenhalli and S. Levy Predicting transcription factor synergism Nucleic Acids Res., October 1, 2002; 30(19): 4278 - 4284. [Abstract] [Full Text] [PDF]

				L.-C. C. Yeh and J. C. Lee Identification of an Osteogenic Protein-1 (Bone Morphogenetic Protein-7)-Responsive Element in the Promoter of the Rat Insulin-Like Growth Factor-Binding Protein-5 Gene Endocrinology, September 1, 2000; 141(9): 3278 - 3286. [Abstract] [Full Text] [PDF]

				D. G. Monroe, D. F. Jin, and M. M. Sanders Estrogen Opposes the Apoptotic Effects of Bone Morphogenetic Protein 7 on Tissue Remodeling Mol. Cell. Biol., July 1, 2000; 20(13): 4626 - 4634. [Abstract] [Full Text]

				W. Ishida, T. Hamamoto, K. Kusanagi, K. Yagi, M. Kawabata, K. Takehara, T. K. Sampath, M. Kato, and K. Miyazono Smad6 Is a Smad1/5-induced Smad Inhibitor. CHARACTERIZATION OF BONE MORPHOGENETIC PROTEIN-RESPONSIVE ELEMENT IN THE MOUSE Smad6 PROMOTER J. Biol. Chem., February 25, 2000; 275(9): 6075 - 6079. [Abstract] [Full Text] [PDF]

				K. Kusanagi, H. Inoue, Y. Ishidou, H. K. Mishima, M. Kawabata, and K. Miyazono Characterization of a Bone Morphogenetic Protein-responsive Smad-binding Element Mol. Biol. Cell, February 1, 2000; 11(2): 555 - 565. [Abstract] [Full Text]

				S.-Z. Lin, B. J. Hoffer, P. Kaplan, Y. Wang, and C. Y. Hsu Osteogenic Protein-1 Protects Against Cerebral Infarction Induced by MCA Ligation in Adult Rats • Editorial Comment Stroke, January 1, 1999; 30(1): 126 - 133. [Abstract] [Full Text] [PDF]