The Most Important Transcriptional Factors of Osteoblastogenesis

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One of the key issues of organogenesis is the understanding of mechanisms underlying the differentiation of progenitor cells into more specialized cells of individual tissues. Recent transcriptomic and proteomic approaches of molecular biology have led to the identification of several factors and mechanisms regulating morphogenesis at the genetic level which affect the function of already differentiated cells. In the last few years, several reports about osteoblastogenesis have been published. This review presents recent findings on the role of the most important transcription factors supporting bone formation.

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  • [1] AMORIM BR OKAMURA H YOSHIDA K QIU L MORIMOTO H HANEJI T. The transcriptional factor Osterix directly interacts with RNA helicase A. Biochem Biophys Res Commun 2007; 355: 347-351.

  • [2] BAE S.C. LEE YH. Phosphorylation acetylation and ubiquitination: the molecular basis of RUNX regulation. Gene 2006; 366: 58-66

  • [3] BAEK WY LEE MA JUNG JW KIM SY AKIYAMA H DE CROMBRUGGHE B KIM JE. Positive Regulation of Adult Bone Formation by Osteoblast-Specific Transcription Factor Osterix. J Bone Miner Res 2009; 24: 1055-1065

  • [4] BESSA PC CASAL M REIS RL. Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic part II (BMP delivery). J Tissue Eng Regen Med 2008; 2: 81-96.

  • [5] BESSA PC CASAL M REIS RL. Bone morphogenetic proteins in tissue engineering: the road from the laboratory to the clinic part I (basic concepts). J Tissue Eng Regen Med 2008; 2: 1-13.

  • [6] BOBIS S JAROCHA D MAJKA M. Mesenchymal stem cells: characteristics and clinical applications. Folia Histochem Cytobiol 2006; 44: 215-230.

  • [7] CADIGAN KM LIU YI. Wnt signaling: complexity at the surface J Cell Science 2006; 119: 395-402

  • [8] CHOI SJ SONG IS RYU OH CHOI SW HART PS WU WW SHEN RF HART TC. A 4 bp deletion mutation in DLX3 enhances osteoblastic differentiation and bone formation in vitro. Bone 2008; 42: 162-171.

  • [9] CHU S FERRO TJ. Sp1: regulation of gene expression by phosphorylation. Gene 2005; 348: 1-11.

  • [10] COOPER JA JR. BAILEY LO CARTER JN CASTIGLIONI CE KOFRON MD KO FK LAURENCIN CT. Evaluation of the anterior cruciate ligament medial collateral ligament achilles tendon and patellar tendon as cell sources for tissue-engineered ligament. Biomaterials 2006; 27: 2747-2754.

  • [11] DE FRUTOS CA DACQUIN R VEGA S JURDIC P MACHUCA-GAYET I NIETO MA. Snail1 controls bone mass by regulating Runx2 and VDR expression during osteoblast differentiation. EMBO J 2009; 28: 686-996.

  • [12] FLORES MV TSANG VW HU W KALEV-ZYLINSKA M POSTLETHWAIT J CROSIER P CROSIER K FISHER S. Duplicate zebrafish runx2 orthologues are expressed in developing skeletal elements. Gene Expr Patterns 2004; 4: 573-581.

  • [13] GIULIANI N COLLA S MORANDI F LAZZARETTI M SALA R BONOMINI S GRANO M COLUCCI S SVALDI M RIZZOLI V. Myeloma cells block RUNX2/CBFA1 activity in human bone marrow osteoblast progenitors and inhibit osteoblast formation and differentiation. Blood 2005; 106: 2472-2483.

  • [14] HANDSCHIN AE EGERMANN M WEDLER V TRENTZ O HEMMI S TRENTZ OA. A comparative analysis of phenotype expression in human osteoblasts from heterotopic ossification and normal bone. Langenbecks Arch Surg 2006; 391: 376-382

  • [15] HASSAN MQ JAVED A MORASSOM MI KARLIN J MONTECINO M van WIJNEN AJ STEIN GS STEIN JL LIAN JB. Dlx3 transcriptional regulation of osteoblast differentiation: temporal recruitment of Msx2 Dlx3 and Dlx5 homeodomain proteins to chromatin of the osteocalcin gene. Mol Cell Biol 2004; 24 :9248-9261

  • [16] HASSAN MQ TARE RS LEE SH MANDEVILLE M MORASSO MI JAVED A VAN WIJNEN AJ STEIN JL STEIN GS LIAN JB. BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network. J Biol Chem 2006; 281: 40515-40526.

  • [17] HASSAN MQ TARE R LEE SH MANDEVILLE M WEINER B MONTECINO M VAN WIJNEN AJ STEIN JL STEIN GS LIAN JB. HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes. Mol Cell Biol 2007; 27: 3337-3352.

  • [18] HASSAN MQ SAINI S GORDON JA VAN WIJNEN AJ MONTECINO M STEIN JL STEIN GS LIAN JB. Molecular switches involving homeodomain proteins HOXA10 and RUNX2 regulate osteoblastogenesis. Cells Tissues Organs 2009; 189: 122-125.

  • [19] HATTA M YOSHIMURA Y DEYAMA Y FUKAMIZU A SUZUKI K. Molecular characterization of the zinc finger transcription factor Osterix. Int J Mol Med 2006; 17: 425-430.

  • [20] ISA ZM SCHNEIDER GB ZAHARIAS R SEABOLD D STANFORD CM. Effects of fluoridemodified titanium surfaces on osteoblast proliferation and gene expression. Int J Oral Maxillofac Implants 2006; 21: 203-211.

  • [21] JEONG JH JIN JS KIM HN KANG SM LIU JC LENGNER CJ OTTO F MUNDLOS S STEIN JL VAN WIJNEN AJ LIAN JB STEIN GS CHOI JY. Expression of Runx2 transcription factor in non-skeletal tissues sperm and brain. J Cell Physiol 2008; 217: 511-517.

  • [22] KASSEM M ABDALLAH BM SAEED H. Osteoblastic cells: Differentiation and transdifferentiation. Arch Biochem Biophys 2008; 473: 183-187

  • [23] KOGA T MATSUI Y ASAGIRI M KODAMA T DE CROMBRUGGHE B NAKASHIMA K TAKAYANAGI H. NFAT and Osterix cooperatively regulate bone formation. Nat Med 2005; 11: 880-885.

  • [24] KOMORI T. Mechanism of transcriptional regulation by Runx2 in osteoblasts. Clin Calcium 2006; 16: 801-807.

  • [25] LEONG WF ZHOU T LIM GL LI B. Protein palmitoylation regulates osteoblast differentiation through BMP-induced osterix expression. PLoS ONE 2009; 4: e4135.

  • [26] LI Y XIAO Z. Advances in Runx2 regulation and its isoforms. Med Hypotheses 2007 68: 169-175

  • [27] LIEDERT A KASPAR D CLAES L IGNATIUS A. Signal transduction pathways involved in mechanical regulation of HB-GAM expression in osteoblastic cells. Biochem Biophys Res Commun 2006; 342: 1070-1076.

  • [28] LIU W TOYOSAWA S FURUICHI T KANATANI N YOSHIDA C LIU Y HIMENO M NARAI S YAMAGUCHI A KOMORI T. Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J Cell Bio. 2001 ;155: 157-166.

  • [29] MAKITA N SUZUKI M ASAMI S TAKAHATA R KOHZAKI D KOBAYASHI S HAKAMAZUKA T HOZUMI N. Two of four alternatively spliced isoforms of RUNX2 control osteocalcin gene expression in human osteoblast cells. Gene 2008; 413: 8-17.

  • [30] MARIE PJ. Transcription factors controlling osteoblastogenesis. Arch Biochem Biophys 2008; 473: 98-105.

  • [31] MASAKI C SCHNEIDER GB ZAHARIAS R SEABOLD D STANFORD C. Effects of implant surface microtopography on osteoblast gene expression. Clin Oral Implants Res 2005; 16: 650-656.

  • [32] MBALAVIELE G SHEIKH S STAIN JP SALAZAR VS CHENG SL CHEN D CIVITELLI R. Beta-catenin and BMP-2 synergize to promote osteoblast differentiation and new bone formation. J Cell Biochem 2005 ;94: 403-418.

  • [33] NAKASHIMA K ZHOU X KUNKEL G ZHANG Z DENG JM BEHRINGER RR DE CROMBRUGGHE B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 2002; 108: 17-29.

  • [34] NEMOTO Y HIGUCHI K BABA O KUDO A TAKANO Y. Multinucleate osteoclasts in medaka as evidence of active bone remodeling. Bone 2007; 40: 399-408.

  • [35] NOHE A KEATING E KNAUS P PETERSEN NO. Signal transduction of bone morphogenetic protein receptors. Cell Signal 2004; 16: 291-299.

  • [36] OKAMURA H AMORIM BR WANG J YOSHIDA K HANEJI T. Calcineurin regulates phosphorylation status of transcription factor osterix. Biochem Biophys Res Commun 2009; 379: 440-444.

  • [37] 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: 3428-3437.

  • [38] OTTO F THORNEL AP CROMPTON T DENZEL A GILMOUR KC ROSEWELL IR STAMP GWH BEDDINGTON RSP MUNDLOS S OLSEN BR SELBY PB OWEN MJ. CbfaI a candidate gene for cleidocranial dysplasia syndrome is essential for osteoblast differentiation and bone development. Cell 1997; 89: 765-771

  • [39] PAZ J WADE K KIYOSHIMA T SODEK J TANG J TU Q YAMAUCHI M CHEN J. Tissueand bone cell-specific expression of bone sialoprotein is directed by a 9.0 kb promoter in transgenic mice. Matrix Biol 2005; 24: 341-352.

  • [40] PHILIPSEN S SUSKE G. A tale of three fingers: the family of mammalian Sp/XKLF transcription factors. Nucleic Acids Res 1999; 27: 2991-3000.

  • [41] PHIMPHILAI M ZHAO Z BOULES H ROCA H FRANCESCHI RT. BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype. J Bone Miner Res 2006; 21: 637-646.

  • [42] RYO HM LEE MH KIM YJ. Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene 2006 366: 51-57

  • [43] SAMEE N GEOFFROY V MARTY C SCHILTZ C VIEUX-ROCHAS M LEVI G DE VERNEJOUL MC. Dlx5 a positive regulator of osteoblastogenesis is essential for osteoblastosteoclast coupling. Am J Pathol 2008; 173: 773-780.

  • [44] WESTENDORF JJ KAHLER RA SCHROEDER TM. Wnt signaling in osteoblasts and bone diseases. Gene 2004; 341: 19-39.

  • [45] WIREN KM TOOMBS AR ZHANG XW. Androgen inhibition of MAP kinase pathway and Elk-1 activation in proliferating osteoblasts. J Mol Endocrinol 2004; 32: 209-226.

  • [46] ZAKANY J DUBOULE D. The role of Hox genes during vertebrate limb development. Curr Opin Genet Dev 2007 ;17: 359-366.

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