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Milona, Maria-athina; Gough, Julie; Edgar, Alasdair (2003)
Publisher: BioMed Central
Journal: BMC Genomics
Languages: English
Types: Article
Subjects: Q2, Biotechnology, QH426-470, Research Article, Genetics, TP248.13-248.65



Osteogenic and chondrocytic differentiation involves a cascade of coordinated transcription factor gene expression that regulates proliferation and matrix protein formation in a defined temporo-spatial manner. Bone morphogenetic protein-2 induces expression of the murine Osterix/Specificity protein-7 (Sp7) transcription factor that is required for osteoblast differentiation and bone formation. Regulation of its expression may prove useful for mediating skeletal repair.


Sp7, the human homologue of the mouse Osterix gene, maps to 12q13.13, close to Sp1 and homeobox gene cluster-C. The first two exons of the 3-exon gene are alternatively spliced, encoding a 431-residue long protein isoform and an amino-terminus truncated 413-residue short protein isoform. The human Sp7 protein is a member of the Sp family having 78% identity with Sp1 in the three, Cys2-His2 type, DNA-binding zinc-fingers, but there is little homology elsewhere. The Sp7 mRNA was expressed in human foetal osteoblasts and craniofacial osteoblasts, chondrocytes and the osteosarcoma cell lines HOS and MG63, but was not detected in adult femoral osteoblasts. Generally, the expression of the short (or beta) protein isoform of Sp7 was much higher than the long (or alpha) protein isoform. No expression of either isoform was found in a panel of other cell types. However, in tissues, low levels of Sp7 were detected in testis, heart, brain, placenta, lung, pancreas, ovary and spleen.


Sp7 expression in humans is largely confined to osteoblasts and chondrocytes, both of which differentiate from the mesenchymal lineage. Of the two protein isoforms, the short isoform is most abundant.

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    • 1. Katagiri T and Takahashi N: Regulatory mechanisms of osteoblast and osteoclast differentiation. Oral Dis 2002, 8:147-159.
    • 2. Xynos ID, Edgar AJ, Buttery LD, Hench LL and Polak JM: Ionic products of bioactive glass dissolution increase proliferation of human osteoblasts and induce insulin-like growth factor II mRNA expression and protein synthesis. Biochem Biophys Res Commun 2000, 276:461-465.
    • 3. Buttery LD, Bourne S, Xynos JD, Wood H, Hughes FJ, Hughes SP, Episkopou V and Polak JM: Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. Tissue Eng 2001, 7:89-99.
    • 4. Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN and O'Keefe RJ: Cyclooxygenase-2 regulates mesenchymal cell differentiation into the osteoblast lineage and is critically involved in bone repair. J Clin Invest 2002, 109:1405-1415.
    • 5. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR and de Crombrugghe B: The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002, 108:17-29.
    • 6. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A and Karsenty G: Increased bone formation in osteocalcin-deficient mice. Nature 1996, 382:448-452.
    • 7. Karsenty G: Bone formation and factors affecting this process. Matrix Biol 2000, 19:85-89.
    • 8. Torrungruang K, Shah R, Alvarez M, Bowen DK, Gerard R, Pavalko FM, Elmendorf JS, Charoonpatrapong K, Hock J, Rhodes SJ and Bidwell JP: Osteoblast intracellular localization of Nmp4 proteins. Bone 2002, 30:931-936.
    • 9. Jheon A, Chen J, Teo W, Ganss B, Sodek J and Cheifetz S: Temporal and spatial expression of a novel zinc finger transcription factor, AJ18, in developing murine skeletal tissues. J Histochem Cytochem 2002, 50:973-982.
    • 10. Jheon AH, Ganss B, Cheifetz S and Sodek J: Characterization of a novel KRAB/C2H2 zinc finger transcription factor involved in bone development. J Biol Chem 2001, 276:18282-18289.
    • 11. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S and Kishimoto T: Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 1997, 89:755-764.
    • 12. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB and Owen MJ: Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 1997, 89:765-771.
    • 13. Harada H, Tagashira S, Fujiwara M, Ogawa S, Katsumata T, Yamaguchi A, Komori T and Nakatsuka M: Cbfa1 isoforms exert functional differences in osteoblast differentiation. J Biol Chem 1999, 274:6972-6978.
    • 14. Yagi K, Tsuji K, Nifuji A, Shinomiya K, Nakashima K, DeCrombrugghe B and Noda M: Bone morphogenetic protein-2 enhances osterix gene expression in chondrocytes. J Cell Biochem 2003, 88:1077-1083.
    • 15. Philipsen S and Suske G: A tale of three fingers: the family of mammalian Sp/XKLF transcription factors. Nucleic Acids Res 1999, 27:2991-3000.
    • 16. Black AR, Black JD and Azizkhan-Clifford J: Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer. J Cell Physiol 2001, 188:143-160.
    • 17. Gollner H, Dani C, Phillips B, Philipsen S and Suske G: Impaired ossification in mice lacking the transcription factor Sp3. Mech Dev 2001, 106:77-83.
    • 18. Kolell KJ and Crawford DL: Evolution of Sp transcription factors. Mol Biol Evol 2002, 19:216-222.
    • 19. Dynan WS and Tjian R: Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II. Cell 1983, 32:669-680.
    • 20. Suske G: The Sp-family of transcription factors. Gene 1999, 238:291-300.
    • 21. Yoo J, Jeong MJ, Kwon BM, Hur MW, Park YM and Han MY: Activation of dynamin I gene expression by Sp1 and Sp3 is required for neuronal differentiation of N1E-115 cells. J Biol Chem 2002, 277:11904-11909.
    • 22. Ghayor C, Chadjichristos C, Herrouin JF, Ala-Kokko L, Suske G, Pujol JP and Galera P: Sp3 represses the Sp1-mediated transactivation of the human COL2A1 gene in primary and de-differentiated chondrocytes. J Biol Chem 2001, 276:36881-36895.
    • 23. Chadjichristos C, Ghayor C, Herrouin JF, Ala-Kokko L, Suske G, Pujol JP and Galera P: Down-regulation of human type II collagen gene expression by transforming growth factor-beta 1 (TGFbeta 1) in articular chondrocytes involves SP3/SP1 ratio. J Biol Chem 2002, 277:43903-43917.
    • 24. Harrison SM, Houzelstein D, Dunwoodie SL and Beddington RS: Sp5, a new member of the Sp1 family, is dynamically expressed during development and genetically interacts with Brachyury. Dev Biol 2000, 227:358-372.
    • 25. Kozak M: An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs. Nucleic Acids Res 1987, 15:8125-8148.
    • 26. Hooft van Huijsduijnen R, Li XY, Black D, Matthes H, Benoist C and Mathis D: Co-evolution from yeast to mouse: cDNA cloning of the two NF-Y (CP-1/CBF) subunits. Embo J 1990, 9:3119-3127.
    • 27. Kawai J, Shinagawa A, Shibata K, Yoshino M, Itoh M, Ishii Y, Arakawa T, Hara A, Fukunishi Y, Konno H, Adachi J, Fukuda S, Aizawa K, Izawa M, Nishi K, Kiyosawa H, Kondo S, Yamanaka I, Saito T, Okazaki Y, Gojobori T, Bono H, Kasukawa T, Saito R, Kadota K, Matsuda H, Ashburner M, Batalov S, Casavant T, Fleischmann W, Gaasterland T, Gissi C, King B, Kochiwa H, Kuehl P, Lewis S, Matsuo Y, Nikaido I, Pesole G, Quackenbush J, Schriml LM, Staubli F, Suzuki R, Tomita M, Wagner L, Washio T, Sakai K, Okido T, Furuno M, Aono H, Baldarelli R, Barsh G, Blake J, Boffelli D, Bojunga N, Carninci P, de Bonaldo MF, Brownstein MJ, Bult C, Fletcher C, Fujita M, Gariboldi M, Gustincich S, Hill D, Hofmann M, Hume DA, Kamiya M, Lee NH, Lyons P, Marchionni L, Mashima J, Mazzarelli J, Mombaerts P, Nordone P, Ring B, Ringwald M, Rodriguez I, Sakamoto N, Sasaki H, Sato K, Schonbach C, Seya T, Shibata Y, Storch KF, Suzuki H, Toyo-oka K, Wang KH, Weitz C, Whittaker C, Wilming L, Wynshaw-Boris A, Yoshida K, Hasegawa Y, Kawaji H, Kohtsuki S and Hayashizaki Y: Functional annotation of a full-length mouse cDNA collection. Nature 2001, 409:685-690.
    • 28. Narayan VA, Kriwacki RW and Caradonna JP: Structures of zinc finger domains from transcription factor Sp1. Insights into sequence-specific protein-DNA recognition. J Biol Chem 1997, 272:7801-7809.
    • 29. Gashler AL, Swaminathan S and Sukhatme VP: A novel repression module, an extensive activation domain, and a bipartite nuclear localization signal defined in the immediate-early transcription factor Egr-1. Mol Cell Biol 1993, 13:4556-4571.
    • 30. Tachibana M, Narumi O, Muguruma K, Yamamoto I, Shinkai Y and Yokota Y: Genomic organization and chromosomal mapping of the basic helix-loop-helix factor OUT (Tcf23/TCF23). Cytogenet Cell Genet 2001, 94:23-25.
    • 31. Yang X and Karsenty G: Transcription factors in bone: developmental and pathological aspects. Trends Mol Med 2002, 8:340-345.
    • 32. Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM and Ralston SH: A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest 2001, 107:899-907.
    • 33. Kalff-Suske M, Kunz J, Grzeschik KH and Suske G: Human Sp3 transcriptional regulator gene (SP3) maps to chromosome 2q31. Genomics 1996, 37:410-412.
    • 34. Takahara T, Kanazu SI, Yanagisawa S and Akanuma H: Heterogeneous Sp1 mRNAs in human HepG2 cells include a product of homotypic trans-splicing. J Biol Chem 2000, 275:38067-38072.
    • 35. Subramaniam M, Harris SA, Oursler MJ, Rasmussen K, Riggs BL and Spelsberg TC: Identification of a novel TGF-beta-regulated gene encoding a putative zinc finger protein in human osteoblasts. Nucleic Acids Res 1995, 23:4907-4912.
    • 36. Blok LJ, Kumar MV and Tindall DJ: Isolation of cDNAs that are differentially expressed between androgen-dependent and androgen-independent prostate carcinoma cells using differential display PCR. Prostate 1995, 26:213-224.
    • 37. Tau KR, Hefferan TE, Waters KM, Robinson JA, Subramaniam M, Riggs BL and Spelsberg TC: Estrogen regulation of a transforming growth factor-beta inducible early gene that inhibits deoxyribonucleic acid synthesis in human osteoblasts. Endocrinology 1998, 139:1346-1353.
    • 38. Kennett SB, Udvadia AJ and Horowitz JM: Sp3 encodes multiple proteins that differ in their capacity to stimulate or repress transcription. Nucleic Acids Res 1997, 25:3110-3117.
    • 39. Ge Y, Matherly LH and Taub JW: Transcriptional regulation of cell-specific expression of the human cystathionine beta - synthase gene by differential binding of Sp1/Sp3 to the -1b promoter. J Biol Chem 2001, 276:43570-43579.
    • 40. de Jong R, van der Heijden J and Meijlink F: DNA-binding specificity of the S8 homeodomain. Nucleic Acids Res 1993, 21:4711-4720.
    • 41. Wang SW and Speck NA: Purification of core-binding factor, a protein that binds the conserved core site in murine leukemia virus enhancers. Mol Cell Biol 1992, 12:89-102.
    • 42. Ducy P and Karsenty G: Two distinct osteoblast-specific cis-acting elements control expression of a mouse osteocalcin gene. Mol Cell Biol 1995, 15:1858-1869.
    • 43. Ducy P, Zhang R, Geoffroy V, Ridall AL and Karsenty G: Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 1997, 89:747-754.
    • 44. Dhamija S and Krebsbach PH: Role of Cbfa1 in ameloblastin gene transcription. J Biol Chem 2001, 276:35159-35164.
    • 45. Banerjee C, Javed A, Choi JY, Green J, Rosen V, van Wijnen AJ, Stein JL, Lian JB and Stein GS: Differential regulation of the two principal Runx2/Cbfa1 n-terminal isoforms in response to bone morphogenetic protein-2 during development of the osteoblast phenotype. Endocrinology 2001, 142:4026-4039.
    • 46. Kim RH and Sodek J: Transcription of the bone sialoprotein gene is stimulated by v-Src acting through an inverted CCAAT box. Cancer Res 1999, 59:565-571.
    • 47. Szymanska J, Mandahl N, Mertens F, Tarkkanen M, Karaharju E and Knuutila S: Ring chromosomes in parosteal osteosarcoma contain sequences from 12q13-15: a combined cytogenetic and comparative genomic hybridization study. Genes Chromosomes Cancer 1996, 16:31-34.
    • 48. Lopes MA, Nikitakis NG, Ord RA and Sauk J., Jr.: Amplification and protein expression of chromosome 12q13-15 genes in osteosarcomas of the jaws. Oral Oncol 2001, 37:566-571.
    • 49. McAllister RM, Gardner MB, Greene AE, Bradt C, Nichols WW and Landing BH: Cultivation in vitro of cells derived from a human osteosarcoma. Cancer 1971, 27:397-402.
    • 50. Billiau A, Edy VG, Heremans H, Van Damme J, Desmyter J, Georgiades JA and De Somer P: Human interferon: mass production in a newly established cell line, MG-63. Antimicrob Agents Chemother 1977, 12:11-15.
    • 51. Xynos ID, Edgar AJ, Buttery LD, Hench LL and Polak JM: Geneexpression profiling of human osteoblasts following treatment with the ionic products of Bioglass 45S5 dissolution. J Biomed Mater Res 2001, 55:151-157.
    • 52. Gough JE, Christian P, Scotchford CA, Rudd CD and Jones IA: Synthesis, degradation, and in vitro cell responses of sodium phosphate glasses for craniofacial bone repair. J Biomed Mater Res 2002, 59:481-489.
    • 53. Harris SA, Enger RJ, Riggs BL and Spelsberg TC: Development and characterization of a conditionally immortalized human fetal osteoblastic cell line. J Bone Miner Res 1995, 10:178-186.
    • 54. Murphy CL and Sambanis A: Effect of oxygen tension and alginate encapsulation on restoration of the differentiated phenotype of passaged chondrocytes. Tissue Eng 2001, 7:791-803.
    • 55. Edgar AJ: The human L-threonine 3-dehydrogenase gene is an expressed pseudogene. BMC Genet 2002, 3:18.
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