Inducible expression of Runx2 results in multiorgan abnormalities in mice

Journal of Cellular Biochemistry

Volumn 112, Issue 2, 2011, Pages 653-665

  He, Nan ^a   Xiao, Zhousheng ^b   Yin, Tong ^c   Stubbs, Jason ^a   Li, Linheng ^c   Quarles, L Darryl ^b  

^a UNIVERSITY OF KANSAS MEDICAL CENTER   (United States)

^b UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER   (United States)

^c STOWERS INSTITUTE FOR MEDICAL RESEARCH   (United States)

Author keywords

ectopic calcification; inducible expression; myeloproliferative disorder; osteopenia; Runx2

Indexed keywords

CRE RECOMBINASE; DOXYCYCLINE; TRANSCRIPTION FACTOR RUNX2;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE; BONE DEVELOPMENT; CALCIFICATION; CONTROLLED STUDY; GENE OVEREXPRESSION; HISTOPATHOLOGY; KIDNEY; LUNG; LYMPHOCYTE; MULTIPLE ORGAN FAILURE; MUSCLE; MYELOPROLIFERATIVE DISORDER; NONHUMAN; OSTEOBLAST; OSTEOPENIA; OVARY; PHENOTYPE; PRIORITY JOURNAL; TRANSGENIC ANIMAL;

ANIMALS; BONE MARROW; CELLS, CULTURED; CORE BINDING FACTOR ALPHA 1 SUBUNIT; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; LIVER; MICE; MICE, TRANSGENIC; MUSCULOSKELETAL ABNORMALITIES; PHENOTYPE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SPLEEN; THYMUS GLAND;

MUS; MUS MUSCULUS;

EID: 79251631940     PISSN: 07302312     EISSN: 10974644     Source Type: Journal    
DOI: 10.1002/jcb.22968     Document Type: Article

References (63)

1. Ahn MY, Bae SC, Maruyama M, Ito Y,. 1996. Comparison of the human genomic structure of the Runt domain-encoding PEBP2/CBFalpha gene family. Gene 168: 279-280.
2. Banerjee C, Javed A, Choi JY, Green J, Rosen V, van Wijnen AJ, Stein JL, Lian JB, Stein GS,. 2001. 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 142: 4026-4039.
3. Belteki G, Haigh J, Kabacs N, Haigh K, Sison K, Costantini F, Whitsett J, Quaggin SE, Nagy A,. 2005. Conditional and inducible transgene expression in mice through the combinatorial use of Cre-mediated recombination and tetracycline induction. Nucleic Acids Res 33: e51.
4. Bendayan D, Barziv Y, Kramer MR,. 2000. Pulmonary calcifications: A review. Respir Med 94: 190-193.
5. Blyth K, Terry A, Mackay N, Vaillant F, Bell M, Cameron ER, Neil JC, Stewart M,. 2001. Runx2: A novel oncogenic effector revealed by in vivo complementation and retroviral tagging. Oncogene 20: 295-302.
6. Blyth K, Cameron ER, Neil JC,. 2005. The RUNX genes: Gain or loss of function in cancer. Nat Rev Cancer 5: 376-387.
7. Blyth K, Vaillant F, Hanlon L, Mackay N, Bell M, Jenkins A, Neil JC, Cameron ER,. 2006. Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. Cancer Res 66: 2195-2201.
8. Bucay N, Sarosi I, Dunstan CR, Morony S, Tarpley J, Capparelli C, Scully S, Tan HL, Xu W, Lacey DL, Boyle WJ, Simonet WS,. 1998. Osteoprotegerin- deficient mice develop early onset osteoporosis and arterial calcification. Genes Dev 12: 1260-1268.
9. Byon CH, Javed A, Dai Q, Kappes JC, Clemens TL, Darley-Usmar VM, McDonald JM, Chen Y,. 2008. Oxidative stress induces vascular calcification through modulation of the osteogenic transcription factor Runx2 by AKT signaling. J Biol Chem 283: 15319-15327.
10. Chillon JM, Mozar A, Six I, Maizel J, Bugnicourt JM, Kamel S, Slama M, Brazier M, Massy ZA,. 2009. Pathophysiological mechanisms and consequences of cardiovascular calcifications: Role of uremic toxicity. Ann Pharm Fr 67: 234-240.
11. Choi JY, Pratap J, Javed A, Zaidi SK, Xing L, Balint E, Dalamangas S, Boyce B, van Wijnen AJ, Lian JB, Stein JL, Jones SN, Stein GS,. 2001. Subnuclear targeting of Runx/Cbfa/AML factors is essential for tissue-specific differentiation during embryonic development. Proc Natl Acad Sci USA 98: 8650-8655.
12. Colla S, Morandi F, Lazzaretti M, Rizzato R, Lunghi P, Bonomini S, Mancini C, Pedrazzoni M, Crugnola M, Rizzoli V, Giuliani N,. 2005. Human myeloma cells express the bone regulating gene Runx2/Cbfa1 and produce osteopontin that is involved in angiogenesis in multiple myeloma patients. Leukemia 19: 2166-2176.
13. Doecke JD, Day CJ, Stephens AS, Carter SL, van Daal A, Kotowicz MA, Nicholson GC, Morrison NA,. 2006. Association of functionally different RUNX2 P2 promoter alleles with BMD. J Bone Miner Res 21: 265-273.
14. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G,. 1997. Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation. Cell 89: 747-754.
15. Ducy P, Starbuck M, Priemel M, Shen J, Pinero G, Geoffroy V, Amling M, Karsenty G,. 1999. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev 13: 1025-1036.
16. Enomoto H, Enomoto-Iwamoto M, Iwamoto M, Nomura S, Himeno M, Kitamura Y, Kishimoto T, Komori T,. 2000. Cbfa1 is a positive regulatory factor in chondrocyte maturation. J Biol Chem 275: 8695-8702.
17. Geoffroy V, Kneissel M, Fournier B, Boyde A, Matthias P,. 2002. High bone resorption in adult aging transgenic mice overexpressing cbfa1/runx2 in cells of the osteoblastic lineage. Mol Cell Biol 22: 6222-6233.
18. Gersbach CA, Le Doux JM, Guldberg RE, Garcia AJ,. 2006. Inducible regulation of Runx2-stimulated osteogenesis. Gene Ther 13: 873-882.
19. Glass DA II, Bialek P, Ahn JD, Starbuck M, Patel MS, Clevers H, Taketo MM, Long F, McMahon AP, Lang RA, Karsenty G,. 2005. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8: 751-764.
20. Hassan MQ, Tare RS, Lee SH, Mandeville M, Morasso MI, Javed A, van Wijnen AJ, Stein JL, Stein GS, Lian JB,. 2006. BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network. J Biol Chem 281: 40515-40526.
21. Ichikawa M, Asai T, Chiba S, Kurokawa M, Ogawa S,. 2004a. Runx1/AML-1 ranks as a master regulator of adult hematopoiesis. Cell Cycle 3: 722-724.
22. Ichikawa M, Asai T, Saito T, Seo S, Yamazaki I, Yamagata T, Mitani K, Chiba S, Ogawa S, Kurokawa M, Hirai H,. 2004b. AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nat Med 10: 299-304.
23. Imai Y, Kurokawa M, Tanaka K, Friedman AD, Ogawa S, Mitani K, Yazaki Y, Hirai H,. 1998. TLE, the human homolog of groucho, interacts with AML1 and acts as a repressor of AML1-induced transactivation. Biochem Biophys Res Commun 252: 582-589.
24. Javed A, Guo B, Hiebert S, Choi JY, Green J, Zhao SC, Osborne MA, Stifani S, Stein JL, Lian JB, van Wijnen AJ, Stein GS,. 2000. Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/ PEBP2(alpha)) dependent activation of tissue-specific gene transcription. J Cell Sci 113 (Pt 12): 2221-2231.
25. Javed A, Barnes GL, Pratap J, Antkowiak T, Gerstenfeld LC, van Wijnen AJ, Stein JL, Lian JB, Stein GS,. 2005. Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo. Proc Natl Acad Sci USA 102: 1454-1459.
26. Jones DC, Wein MN, Oukka M, Hofstaetter JG, Glimcher MJ, Glimcher LH,. 2006. Regulation of adult bone mass by the zinc finger adapter protein Schnurri-3. Science 312: 1223-1227.
27. Kanatani N, Fujita T, Fukuyama R, Liu W, Yoshida CA, Moriishi T, Yamana K, Miyazaki T, Toyosawa S, Komori T,. 2006. Cbf beta regulates Runx2 function isoform-dependently in postnatal bone development. Dev Biol 296: 48-61.
28. 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, Kishimoto T,. 1997. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89: 755-764.
29. Kuo YH, Zaidi SK, Gornostaeva S, Komori T, Stein GS, Castilla LH,. 2009. Runx2 induces acute myeloid leukemia in cooperation with Cbfbeta-SMMHC in mice. Blood 113: 3323-3332.
30. Kurokawa M, Hirai H,. 2003. Role of AML1/Runx1 in the pathogenesis of hematological malignancies. Cancer Sci 94: 841-846.
31. Lindenmuth DM, van Wijnen AJ, Hiebert S, Stein JL, Lian JB, Stein GS,. 1997. Subcellular partitioning of transcription factors during osteoblast differentiation: Developmental association of the AML/CBF alpha/PEBP2 alpha-related transcription factor-NMP-2 with the nuclear matrix. J Cell Biochem 66: 123-132.
32. Liu W, Toyosawa S, Furuichi T, Kanatani N, Yoshida C, Liu Y, Himeno M, Narai S, Yamaguchi A, Komori T,. 2001. Overexpression of Cbfa1 in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J Cell Biol 155: 157-166.
33. Maruyama Z, Yoshida CA, Furuichi T, Amizuka N, Ito M, Fukuyama R, Miyazaki T, Kitaura H, Nakamura K, Fujita T, Kanatani N, Moriishi T, Yamana K, Liu W, Kawaguchi H, Nakamura K, Komori T,. 2007. Runx2 determines bone maturity and turnover rate in postnatal bone development and is involved in bone loss in estrogen deficiency. Dev Dyn 236: 1876-1890.
34. Mathew S, Tustison KS, Sugatani T, Chaudhary LR, Rifas L, Hruska KA,. 2008. The mechanism of phosphorus as a cardiovascular risk factor in CKD. J Am Soc Nephrol 19: 1092-1105.
35. Mercado-Pimentel ME, Hubbard AD, Runyan RB,. 2007. Endoglin and Alk5 regulate epithelial-mesenchymal transformation during cardiac valve formation. Dev Biol 304: 420-432.
36. Merciris D, Marty C, Collet C, de Vernejoul MC, Geoffroy V,. 2007. Overexpression of the transcriptional factor Runx2 in osteoblasts abolishes the anabolic effect of parathyroid hormone in vivo. Am J Pathol 170: 1676-1685.
37. Meyers S, Lenny N, Sun W, Hiebert SW,. 1996. AML-2 is a potential target for transcriptional regulation by the t(8;21) and t(12;21) fusion proteins in acute leukemia. Oncogene 13: 303-312.
38. Ogawa E, Maruyama M, Kagoshima H, Inuzuka M, Lu J, Satake M, Shigesada K, Ito Y,. 1993. PEBP2/PEA2 represents a family of transcription factors homologous to the products of the Drosophila runt gene and the human AML1 gene. Proc Natl Acad Sci USA 90: 6859-6863.
39. Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ,. 1997. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89: 765-771.
40. Qiao M, Shapiro P, Fosbrink M, Rus H, Kumar R, Passaniti A,. 2006. Cell cycle-dependent phosphorylation of the RUNX2 transcription factor by cdc2 regulates endothelial cell proliferation. J Biol Chem 281: 7118-7128.
41. Quack I, Vonderstrass B, Stock M, Aylsworth AS, Becker A, Brueton L, Lee PJ, Majewski F, Mulliken JB, Suri M, Zenker M, Mundlos S, Otto F,. 1999. Mutation analysis of core binding factor A1 in patients with cleidocranial dysplasia. Am J Hum Genet 65: 1268-1278.
42. Satake M, Nomura S, Yamaguchi-Iwai Y, Takahama Y, Hashimoto Y, Niki M, Kitamura Y, Ito Y,. 1995. Expression of the Runt domain-encoding PEBP2 alpha genes in T cells during thymic development. Mol Cell Biol 15: 1662-1670.
43. Selvamurugan N, Jefcoat SC, Kwok S, Kowalewski R, Tamasi JA, Partridge NC,. 2006. Overexpression of Runx2 directed by the matrix metalloproteinase-13 promoter containing the AP-1 and Runx/RD/Cbfa sites alters bone remodeling in vivo. J Cell Biochem 99: 545-557.
44. Shore EM, Kaplan FS,. 2008. Insights from a rare genetic disorder of extra-skeletal bone formation, fibrodysplasia ossificans progressiva (FOP). Bone 43: 427-433.
45. Speer MY, Yang HY, Brabb T, Leaf E, Look A, Lin WL, Frutkin A, Dichek D, Giachelli CM,. 2009. Smooth muscle cells give rise to osteochondrogenic precursors and chondrocytes in calcifying arteries. Circ Res 104: 733-741.
46. Speer MY, Li X, Hiremath PG, Giachelli CM,. 2010. Runx2/Cbfa1, but not loss of myocardin, is required for smooth muscle cell lineage reprogramming toward osteochondrogenesis. J Cell Biochem 110: 935-947.
47. Stewart M, Terry A, Hu M, O'Hara M, Blyth K, Baxter E, Cameron E, Onions DE, Neil JC,. 1997. Proviral insertions induce the expression of bone-specific isoforms of PEBP2alphaA (CBFA1): Evidence for a new myc collaborating oncogene. Proc Natl Acad Sci USA 94: 8646-8651.
48. Stubbs JR, Liu S, Tang W, Zhou J, Wang Y, Yao X, Quarles LD,. 2007. Role of hyperphosphatemia and 1,25-dihydroxyvitamin D in vascular calcification and mortality in fibroblastic growth factor 23 null mice. J Am Soc Nephrol 18: 2116-2124.
49. Sun L, Vitolo MI, Qiao M, Anglin IE, Passaniti A,. 2004. Regulation of TGFbeta1-mediated growth inhibition and apoptosis by RUNX2 isoforms in endothelial cells. Oncogene 23: 4722-4734.
50. Thirunavukkarasu K, Mahajan M, McLarren KW, Stifani S, Karsenty G,. 1998. Two domains unique to osteoblast-specific transcription factor Osf2/Cbfa1 contribute to its transactivation function and its inability to heterodimerize with Cbfbeta. Mol Cell Biol 18: 4197-4208.
51. Ueta C, Iwamoto M, Kanatani N, Yoshida C, Liu Y, Enomoto-Iwamoto M, Ohmori T, Enomoto H, Nakata K, Takada K, Kurisu K, Komori T,. 2001. Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes. J Cell Biol 153: 87-100.
52. Vaillant F, Blyth K, Terry A, Bell M, Cameron ER, Neil J, Stewart M,. 1999. A full-length Cbfa1 gene product perturbs T-cell development and promotes lymphomagenesis in synergy with myc. Oncogene 18: 7124-7134.
53. van der Deen M, Akech J, Wang T, FitzGerald TJ, Altieri DC, Languino LR, Lian JB, van Wijnen AJ, Stein JL, Stein GS,. 2010. The cancer-related Runx2 protein enhances cell growth and responses to androgen and TGFbeta in prostate cancer cells. J Cell Biochem 109: 828-837.
54. Wang Q, Stacy T, Binder M, Marin-Padilla M, Sharpe AH, Speck NA,. 1996. Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proc Natl Acad Sci USA 93: 3444-3449.
55. Wang Y, Belflower RM, Dong YF, Schwarz EM, O'Keefe RJ, Drissi H,. 2005. Runx1/AML1/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis. J Bone Miner Res 20: 1624-1636.
56. Xiao ZS, Hinson TK, Quarles LD,. 1999. Cbfa1 isoform overexpression upregulates osteocalcin gene expression in non-osteoblastic and pre-osteoblastic cells. J Cell Biochem 74: 596-605.
57. Xiao ZS, Hjelmeland AB, Quarles LD,. 2004. Selective deficiency of the "bone-related" Runx2-II unexpectedly preserves osteoblast-mediated skeletogenesis. J Biol Chem 279: 20307-20313.
58. Xiao Z, Awad HA, Liu S, Mahlios J, Zhang S, Guilak F, Mayo MS, Quarles LD,. 2005. Selective Runx2-II deficiency leads to low-turnover osteopenia in adult mice. Dev Biol 283: 345-356.
59. Xiao Z, Zhang S, Mahlios J, Zhou G, Magenheimer BS, Guo D, Dallas SL, Maser R, Calvet JP, Bonewald L, Quarles LD,. 2006. Cilia-like structures and polycystin-1 in osteoblasts/osteocytes and associated abnormalities in skeletogenesis and Runx2 expression. J Biol Chem 281: 30884-30895.
60. Yoshida CA, Komori T,. 2005. Role of Runx proteins in chondrogenesis. Crit Rev Eukaryot Gene Expr 15: 243-254.
61. Zaidi SK, Javed A, Choi JY, van Wijnen AJ, Stein JL, Lian JB, Stein GS,. 2001. A specific targeting signal directs Runx2/Cbfa1 to subnuclear domains and contributes to transactivation of the osteocalcin gene. J Cell Sci 114: 3093-3102.
62. Zhang J, Grindley JC, Yin T, Jayasinghe S, He XC, Ross JT, Haug JS, Rupp D, Porter-Westpfahl KS, Wiedemann LM, Wu H, Li L,. 2006. PTEN maintains haematopoietic stem cells and acts in lineage choice and leukaemia prevention. Nature 441: 518-522.
63. Zhang S, Xiao Z, Luo J, He N, Mahlios J, Quarles LD,. 2009. Dose-dependent effects of Runx2 on bone development. J Bone Miner Res 24: 1889-1904.