Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling

Journal of Cell Biology

Volumn 166, Issue 1, 2004, Pages 85-95

  Fujita, Takashi ^a   Azuma, Yasutaka ^b   Fukuyama, Ryo ^c,d   Hattori, Yuji ^a   Yoshida, Carolina ^d,e   Koida, Masao ^a   Ogita, Kiyokazu ^a   Komori, Toshihisa ^d  

^a SETSUNAN UNIVERSITY   (Japan)

^b OSAKA DENTAL UNIVERSITY   (Japan)

^c HIROSHIMA INTERNATIONAL UNIVERSITY   (Japan)

^d NAGASAKI UNIVERSITY GRADUATE SCHOOL OF BIOMEDICAL SCIENCES   (Japan)

^e OSAKA UNIVERSITY   (Japan)

Author keywords

Cbfa1; Chemotaxis; IGF; MEK; myrAkt

Indexed keywords

2 MORPHOLINO 8 PHENYLCHROMONE; ADENOVIRUS VECTOR; ANTIBODY; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; PROTEIN P100; PROTEIN P110BETA; PROTEIN P85; SOMATOMEDIN C; TRANSCRIPTION FACTOR RUNX2; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CARTILAGE CELL; CELL DIFFERENTIATION; CELL LINE; CELL MIGRATION; ENZYME SUBUNIT; NONHUMAN; OSTEOBLAST; PRIORITY JOURNAL; PROTEIN DNA BINDING; PROTEIN EXPRESSION; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; UPREGULATION;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ADENOVIRIDAE; ANIMALS; BLOTTING, WESTERN; CELL DIFFERENTIATION; CELL LINE; CELL MOVEMENT; CELL NUCLEUS; CHONDROCYTES; CHROMATIN; CHROMONES; CORE BINDING FACTOR ALPHA 1 SUBUNIT; DNA; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; GENES, DOMINANT; GENES, REPORTER; GENETIC VECTORS; IMMUNOHISTOCHEMISTRY; IN SITU HYBRIDIZATION; MICE; MICE, INBRED C3H; MICE, MUTANT STRAINS; MORPHOLINES; MUTATION; NEOPLASM PROTEINS; OSTEOBLASTS; PRECIPITIN TESTS; PROTEIN BINDING; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS; TRANSFECTION; UP-REGULATION;

ADENOVIRIDAE; ANIMALIA;

EID: 3142707223     PISSN: 00219525     EISSN: None     Source Type: Journal    
DOI: 10.1083/jcb.200401138     Document Type: Article

References (37)

1. Akiyama, H., T. Kanno, H. Ito, A. Terry, J. Neil, Y. Ito, and T. Nakamura. 1999. Positive and negative regulation of chondrogenesis by splice variants of PEBP2αA/CBFa1 in clonal mouse EC cells, ATDC5. J. Cell. Physiol. 181:169-178.
2. Akune, T., N. Ogata, K. Hoshi, N. Kubota, Y. Terauchi, K. Tobe, H. Takagi, Y. Azuma, T. Kadowaki, K. Nakamura, et al. 2002. Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts. J. Cell Biol. 159:147-156.
3. Banerjee, C., L.R. McCabe, J. Choi, S.W. Hiebert, J.L. Stein, G.S. Stein, and J.B. Lian. 1997. Runt homology domain proteins in osteoblast differentiation: AML3/CBFA1 is a major component of a bone-specific complex. J. Cell. Biochem. 66:1-8.
4. Bi, W., J.M. Deng, Z. Zhang, R.R. Behringer, and B. de Crombrugghe. 1999. Sox9 is required for cartilage formation. Nat. Genet. 22:85-89.
5. Ducy, P., R. Zhang, V. Geoffrey, A.L. Ridall, and G. Karsenty. 1997. Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell. 89:747-754.
6. Enomoto, H., M. Enomoro-Iwamoto, M. Iwamoto, S. Nomura, M. Himeno, Y. Kitamura, T. Kishimoto, and T. Komori. 2000. Cbfa1 is a positive regulatory factor in chondrocyte maturation. J. Biol. Chem. 275:8695-8702.
7. Fujio, Y., K. Guo, T. Mano, Y. Mitsuuchi, J.R. Testa, and K. Walsh. 1999. Cell cycle withdrawal promotes myogenic induction of Akt, a positive modulator of myocyte survival. Mol. Cell. Biol. 19:5073-5082.
8. Fukuyama, R., T. Fujita, Y. Azuma, T. Hirano, H. Nakamura, M. Koida, and T. Komori. 2004. Statins inhibit osteoblast migration by inhibiting Rac-Akt signaling. Biochem. Biophys. Res. Commun. 315:636-642.
9. Ghosh-Choudhury, N., S.L. Abboud, R. Nishimura, A. Celeste, L. Mahimainathan, and G.G. Choudhury. 2002. Requirement of BMP-2-induced phosphatidylinositol 3-kinase and Akt serine/threonine kinase in osteoblast differentiation and Smad-dependent BMP-2 gene transcription. J. Biol. Chem. 277:33361-33368.
10. Harada, H., S. Tagashira, M. Fujiwara, S. Ogawa, T. Katsumata, A. Yamaguchi, T. Komori, and M. Nakatsuka. 1999. Cbfa1 isoforms exert functional differences in osteoblast differentiation. J. Biol. Chem. 274:6972-6978.
11. Hidaka, K., T. Kanematsu, H. Takeuchi, M. Nakata, U. Kikkawa, and M. Hirata. 2001. Involvement of the phosphoinositide 3-kinase/protein kinase B signaling pathway in insulin/IGF-I-induced chondrogenesis of the mouse embryonal carcinoma-derived cell line ATDC5. Int. J. Biochem. Cell Biol. 33:1094-1103.
12. Huang, B.K., L.A. Golden, G. Tarjan, L.D. Madison, and P.H. Stern. 2000. Insulin-like growth factor I production is essential for anabolic effects of thyroid hormone in osteoblasts. J. Bone Miner. Res. 15:188-197.
13. Inada, M., T. Yasui, S. Nomura, S. Miyake, K. Deguchi, M. Himeno, M. Sato, H. Yamagiwa, T. Kimura, N. Yasui, et al. 1999. Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev. Dyn. 214:279-290.
14. Kaliman, P., F. Vinals, X. Testar, M. Palacin, and A. Zorzano. 1996. Phosphatidylinositol 3-kinase inhibitors block differentiation of skeletal muscle cells. J. Biol. Chem. 271:19146-19151.
15. Karaplis, A.C. 2002. Embryonic development of bone and the molecular regulation of intramembranous and endochondral bone formation. In Principles of Bone Biology. J.P. Bilezikian, L.G. Raisz, and G.A. Rodan, editors. Academic Press, London. 33-58.
16. Kawahata, H., T. Kikkawa, Y. Higashibata, T. Sakuma, M. Huening, M. Sato, M. Sugimoto, K. Kuriyama, K. Terai, Y. Kitamura, et al. 2003. Enhanced expression of Runx2/PEBP2alphaA/CBFA1/AML3 during fracture healing. J. Orthop. Sci. 8:102-108.
17. Kim, I.S., F. Otto, B. Zabel, and S. Mundlos. 1999. Regulation of chondrocyte differentiation by cbfa1. Mech. Dev. 80:159-170.
18. Kobayashi, H., Y. Gao, C. Ueta, A. Yamaguchi, and T. Komori. 2000. Multilineage differentiation of Cbfa1-deficient calvarial cells in vitro. Biochem. Biophys. Res. Commun. 273:630-636.
19. Komori, T. 2002. Runx2, a multifunctional transcription factor in skeletal development. J. Cell. Biochem. 87:1-8.
20. Komori, T., H. Yagi, S. Nomura, A. Yamaguchi, K. Sasaki, K. Deguchi, Y. Shimizu, R.T. Bronson, Y.H. Gao, M. Inada, et al. 1997. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 89:755-764.
21. Liu, J.P., J. Baker, A.S. Perkins, E.J. Robertson, and A. Efstratiadis. 1993. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell. 75:59-72.
22. Liu, W., S. Toyosawa, T. Furuichi, N. Kanatani, C. Yoshida, Y. Liu, M. Himeno, S. Narai, A. Yamaguchi, and T. Komori. 2001. Overexpression of Cbfal in osteoblasts inhibits osteoblast maturation and causes osteopenia with multiple fractures. J. Cell Biol. 155:157-166.
23. Nakashima, K., X. Zhou, G. Kunkel, Z. Zhang, J.M. Deng, R.R. Behringer, and B. de Crombrugghe. 2002. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 108:17-29.
24. Ogata, N., D. Chikazu, N. Kubota, Y. Terauchi, K. Tobe, Y. Azuma, T. Ohta, T. Kadowaki, K. Nakamura, and H. Kawaguchi. 2000. Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover. J. Clin. Invest. 105:935-943.
25. Otto, F., A.P. Thornell, T. Crompton, A. Denzel, K.C. Gilmour, I.R. Rosewell, G.W. Stamp, R.S. Beddington, S. Mundlos, B.R. Olsen, et al. 1997. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell. 89:765-771.
26. Peng, X.D., P.Z. Xu, M.L. Chen, A. Hahn-Windgassen, J. Skeen, J. Jacobs, D. Sundararajan, W.S. Chen, S.E. Crawford, K.G. Coleman, et al. 2003. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev. 17:1352-1365.
27. Ridley, A.J., M.A. Schwartz, K. Burridge, R.A. Firtel, M.H. Ginsberg, G. Borisy, J.T. Parsons, and A.R. Horwitz. 2003. Cell migration: integrating signals from front to back. Science. 302:1704-1709.
28. Sakaue, H., W. Ogawa, M. Matsumoto, S. Kuroda, M. Takata, T. Sugimoto, B.M. Spiegelman, and M. Kasuga. 1998. Posttranscriptional control of adipocyte differentiation through activation of phosphoinositide 3-kinase. J. Biol. Chem. 273:28945-28952.
29. Scheid, M.P., and J.R. Woodgett. 2001. PKB/AKT: functional insights from genetic models. Nat. Rev. Mol. Cell Biol. 2:760-768.
30. Selvamurugan, N., M.R. Pulumati, D.R. Tyson, and N.C. Partridge. 2000. Parathyroid hormone regulation of the rat collagenase-3 promoter by protein kinase A-dependent transactivation of core binding factor alpha1. J. Biol. Chem. 275:5037-5042.
31. Shukunami, C., C. Shigeno, T. Atsumi, K. Ishizeki, F. Suzuki, and Y. Hiraki. 1996. Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: differentiation-dependent gene expression of parathyroid hormone (PTH)/PTH-related peptide receptor. J. Cell Biol. 133:457-468.
32. Smits, P., P. Li, J. Mandel, Z. Zhang, J.M. Deng, R.R. Behringer, B. de Croumbrugghe, and V. Lefebvre. 2001. The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev. Cell. 1:277-290.
33. Ueta, C., M. Iwamoto, N. Kanatani, C. Yoshida, Y. Liu, M. Enomoto-Iwamoto, T. Ohmori, H. Enomoto, K. Nakata, K. Takada, et al. 2001. Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes. J. Cell Biol. 153:87-99.
34. Wee, H.J., G. Huang, K. Shigesada, and Y. Ito. 2002. Serine phosphorylation of RUNX2 with novel potential functions as negative regulatory mechanisms. EMBO Rep. 3:967-974.
35. Xiao, G., D. Jiang, P. Thomas, M.D. Benson, K. Guan, G. Karsenty, and R.T. Franceschi. 2000. MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J. Biol. Chem. 275:4453-4459.
36. Yoshida, C.A., T. Furuichi, T. Fujita, R. Fukuyama, N. Kanatani, S. Kobayashi, M. Satake, K. Takada, and T. Komori. 2002. Core-binding factor beta interacts with Runx2 and is required for skeletal development. Nat. Genet. 32:633-638.
37. Yoshida, C.A., H. Yamamoto, T. Fujita, T. Furuichi, K. Ito, K. Inoue, K. Yamana, A. Zanma, K. Takada, Y. Ito, and T. Komori. 2004. Runx2 and Runx3 are essential for chondrocyte maturation and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev. 18:952-963.