Regulation of bone and cartilage development by network between BMP signalling and transcription factors

Journal of Biochemistry

Volumn 151, Issue 3, 2012, Pages 247-254

  Nishimura, Riko ^a   Hata, Kenji ^a   Matsubara, Takuma ^a   Wakabayashi, Makoto ^a   Yoneda, Toshiyuki ^a  

^a OSAKA UNIVERSITY   (Japan)

Author keywords

BMP; bone; cartilage; transcription factors

Indexed keywords

BONE MORPHOGENETIC PROTEIN; SMAD PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR DLX5; TRANSCRIPTION FACTOR MSX2; TRANSCRIPTION FACTOR OSTERIX; TRANSCRIPTION FACTOR RUNX2; TRANSCRIPTION FACTOR SOX9;

BONE DEVELOPMENT; CARTILAGE CELL; CELL DIFFERENTIATION; CHONDROGENESIS; ENDOPLASMIC RETICULUM STRESS; FEEDBACK SYSTEM; HUMAN; NONHUMAN; OSSIFICATION; OSTEOCYTE; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; BONE AND BONES; BONE MORPHOGENETIC PROTEINS; CARTILAGE; HUMANS; SIGNAL TRANSDUCTION; TRANSCRIPTION FACTORS;

EID: 84858200481     PISSN: 0021924X     EISSN: 17562651     Source Type: Journal    
DOI: 10.1093/jb/mvs004     Document Type: Review

References (78)

1. Kronenberg, H.M. (2003) Developmental regulation of the growth plate. Nature 423, 332-336 (Pubitemid 40852707)
2. Karsenty, G. (2003) The complexities of skeletal biology. Nature 423, 316-318 (Pubitemid 40852704)
3. Komori, T. (2011) Signaling networks in RUNX2-dependent bone development. J. Cell. Biochem. 112, 750-755
4. Nishimura, R., Hata, K., Ikeda, F., Ichida, F., Shimoyama, A., Matsubara, T., Wada, M., Amano, K., and Yoneda, T. (2008) Signal transduction and transcriptional regulation during mesenchymal cell differentiation. J. Bone Miner. Metab. 26, 203-212 (Pubitemid 351677844)
5. de Crombrugghe, B., Lefebvre, V., Behringer, R.R., Bi, W., Murakami, S., and Huang, W. (2000) Transcriptional mechanisms of chondrocyte differentiation. Matrix Biol. 19, 389-394
6. Heldin, C.H., Miyazono, K., and ten Dijke, P. (1997) TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 390, 465-471 (Pubitemid 28013118)
7. Miyazono, K., Maeda, S., and Imamura, T. (2005) BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 16, 251-263 (Pubitemid 40910315)
8. Massagué, J., Seoane, J., and Wotton, D. (2005) Smad transcription factors. Genes Dev. 19, 2783-2810 (Pubitemid 41739965)
9. Miyazono, K., Kamiya, Y., and Morikawa, M. (2010) Bone morphogenetic protein receptors and signal transduction. J. Biochem. 147, 35-51
10. Zhao, M., Harris, S.E., Horn, D., Geng, Z., Nishimura, R., Mundy, G.R., and Chen, D. (2002) Bone morphogenetic protein receptor signaling is necessary for normal murine postnatal bone formation. J. Cell Biol. 157, 1049-1060 (Pubitemid 34839779)
11. Nishimura, R., Kato, Y., Chen, D., Harris, S.E., Mundy, G.R., and Yoneda, T. (1998) Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12. J. Biol. Chem. 273, 1872-1879 (Pubitemid 28069228)
12. Kawai, S., Faucheu, C., Gallea, S., Spinella-Jaegle, S., Atfi, A., Baron, R., and Roman, S.R. (2000) Mouse smad8 phosphorylation downstream of BMP receptors ALK-2, ALK-3, and ALK-6 induces its association with Smad4 and transcriptional activity. Biochem. Biophys. Res. Commun. 271, 682-687 (Pubitemid 30444688)
13. Fujii, M., Takeda, K., Imamura, T., Aoki, H., Sampath, T.K., Enomoto, S., Kawabata, M., Kato, M., Ichijo, H., and Miyazono, K. (1999) Roles of bone morphogenetic protein type I receptors and Smad proteins in osteoblast and chondroblast differentiation. Mol. Biol. Cell 10, 3801-3813 (Pubitemid 29534026)
14. Mundlos, S., Otto, F., Mundlos, C., Mulliken, J.B., Aylsworth, A.S., Albright, S., Lindhout, D., Cole, W.G., Henn, W., Knoll, J.H., Owen, M.J., Mertelsmann, R., Zabel, B.U., and Olsen, B.R. (1997) Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell 89, 773-779 (Pubitemid 27516180)
15. Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., Shimizu, Y., Bronson, R.T., Gao, Y.H., Inada, M., Sato, M., Okamoto, R., Kitamura, Y., Yoshiki, S., and 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 (Pubitemid 27516178)
16. Otto, F., Thornell, A.P., Crompton, T., Denzel, A., Gilmour, K.C., Rosewell, I.R., Stamp, G.W., Beddington, R.S., Mundlos, S., Olsen, B.R., elby, P.B., and Owen, M.J. (1997) Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89, 765-771 (Pubitemid 27516179)
17. Ducy, P., Zhang, R., Geoffroy, V., Ridall, A.L., and Karsenty, G. (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89, 747-754 (Pubitemid 27516177)
18. Nishimura, R., Hata, K., Harris, S.E., Ikeda, F., and Yoneda, T. (2002) Core-binding factor alpha 1 (Cbfa1) induces osteoblastic differentiation of C2C12 cells without interactions with Smad1 and Smad5. Bone 31, 303-312 (Pubitemid 34814965)
19. Lee, K.S., Kim, H.J., Li, Q.L., Chi, X.Z., Ueta, C., Komori, T., Wozney, J.M., Kim, E.G., Choi, J.Y., Ryoo, H.M., and Bae, S.C. (2000) Runx2 is a common target of transforming growth factor beta1 and bone morphogenetic protein 2, and cooperation between Runx2 and Smad5 induces osteoblast-specific gene expression in the pluripotent mesenchymal precursor cell line C2C12. Mol. Cell. Biol. 20, 8783-8792 (Pubitemid 32245911)
20. Hanai, J., Chen, L.F., Kanno, T., Ohtani-Fujita, N., Kim, W.Y., Guo, W.H., Imamura, T., Ishidou, Y., Fukuchi, M., Shi, M.J., Stavnezer, J., Kawabata, M., Miyazono, K., and Ito, Y. (1999) Interaction and functional cooperation of PEBP2/CBF with Smads. Synergistic induction of the immunoglobulin germline Calpha promoter. J. Biol. Chem. 274, 31577-31582
21. Zhang, Y.W., Yasui, N., Ito, K., Huang, G., Fujii, M., Hanai, J., Nogami, H., Ochi, T., Miyazono, K., and Ito, Y. (2000) A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia. Proc. Natl Acad. Sci. USA 97, 10549-10554
22. Hata, K., Nishimura, R., Ueda, M., Ikeda, F., Matsubara, T., Ichida, F., Hisada, K., Nokubi, T., Yamaguchi, A., and Yoneda, T. (2005) A CCAAT/enhancer binding protein beta isoform, liver-enriched inhibitory protein, regulates commitment of osteoblasts and adipocytes. Mol. Cell. Biol. 25, 1971-1979 (Pubitemid 40280159)
23. Shirakawa, K., Maeda, S., Gotoh, T., Hayashi, M., Shinomiya, K., Ehata, S., Nishimura, R., Mori, M., Onozaki, K., Hayashi, H., Uematsu, S., Akira, S., Ogata, E., Miyazono, K., and Imamura, T. (2006) CC AAT/enhancer-binding protein homologous protein (CHOP) regulates osteoblast differentiation. Mol. Cell. Biol. 26, 6105-6116 (Pubitemid 44204529)
24. Nakashima, K., Zhou, X., Kunkel, G., Zhang, Z., Deng, J.M., Behringer, R.R., and de Crombrugghe, B. (2002) The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108, 17-29 (Pubitemid 34137009)
25. Matsubara, T., Kida, K., Yamaguchi, A., Hata, K., Ichida, F., Meguro, H., Aburatani, H., Nishimura, R., and Yoneda, T. (2008) BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation. J. Biol. Chem. 283, 29119-29125
26. Towler, D.A., Rutledge, S.J., and Rodan, G.A. (1994) Msx-2/Hox 8.1: a transcriptional regulator of the rat osteocalcin promoter. Mol. Endocrinol. 8, 1484-1493 (Pubitemid 24370197)
27. Ryoo, H.M., Hoffmann, H.M., Beumer, T., Frenkel, B., Towler, D.A., Stein, G.S., Stein, J.L., van Wijnen, A.J., and Lian, J.B. (1997) Stage-specific expression of Dlx-5 during osteoblast differentiation: involvement in regulation of osteocalcin gene expression. Mol. Endocrinol. 11, 1681-1694 (Pubitemid 27435416)
28. Satokata, I., Ma, L., Ohshima, H., Bei, M., Woo, I., Nishizawa, K., Maeda, T., Takano, Y., Uchiyama, M., Heaney, S., Peters, H., Tang, Z., Maxson, R., and Maas, R. (2000) Msx2 deficiency in mice causes pleiotropic defects in bone growth and ectodermal organ formation. Nat. Genet. 24, 391-395 (Pubitemid 30187439)
29. Wilkie, A.O., Tang, Z., Elanko, N., Walsh, S., Twigg, S.R., Hurst, J.A., Wall, S.A., Chrzanowska, K.H., and Maxson, R.E. Jr (2000) Functional haploinsufficiency of the human homeobox gene MSX2 causes defects in skull ossification. Nat. Genet. 24, 387-390 (Pubitemid 30187438)
30. Wuyts, W., Reardon, W., Preis, S., Homfray, T., Rasore-Quartino, A., Christians, H., Willems, P.J., and Van Hul, W. (2000) Identification of mutations in the MSX2 homeobox gene in families affected with foramina parietalia permagna. Hum. Mol. Genet. 9, 1251-1255 (Pubitemid 30248612)
31. Cheng, S.L., Shao, J.S., Charlton-Kachigian, N., Loewy, A.P., and Towler, D.A. (2003) MSX2 promotes osteogenesis and suppresses adipogenic differentiation of multipotent mesenchymal progenitors. J. Biol. Chem. 278, 45969-45977 (Pubitemid 37432744)
32. Ichida, F., Nishimura, R., Hata, K., Matsubara, T., Ikeda, F., Hisada, K., Yatani, H., Cao, X., Komori, T., Yamaguchi, A., and Yoneda, T. (2004) Reciprocal roles of MSX2 in regulation of osteoblast and adipocyte differentiation. J. Biol. Chem. 279, 34015-34022 (Pubitemid 39063053)
33. Cheng, S.L., Shao, J.S., Cai, J., Sierra, O.L., and Towler, D.A. (2008) Msx2 exerts bone anabolism via canonical Wnt signaling. J. Biol. Chem. 283, 20505-20522
34. Acampora, D., Merlo, G.R., Paleari, L., Zerega, B., Postiglione, M.P., Mantero, S., Bober, E., Barbieri, O., Simeone, A., and Levi, G. (1999) Craniofacial, vestibular and bone defects in mice lacking the Distal-less-related gene Dlx5. Development 126, 3795-3809 (Pubitemid 29440478)
35. Robledo, R.F. and Lufkin, T. (2006) Dlx5 and Dlx6 homeobox genes are required for specification of the mammalian vestibular apparatus. Genesis 44, 425-437 (Pubitemid 44454048)
36. Jeong, J., Li, X., McEvilly, R.J., Rosenfeld, M.G., Lufkin, T., and Rubenstein, J.L. (2008) Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs. Development 135, 2905-2916
37. Takase, M., Imamura, T., Sampath, T.K., Takeda, K., Ichijo, H., Miyazono, K., and Kawabata, M. (1998) Induction of Smad6 mRNA by bone morphogenetic proteins. Biochem. Biophys. Res. Commun. 244, 26-29 (Pubitemid 28419894)
38. Murakami, G., Watabe, T., Takaoka, K., Miyazono, K., and Imamura, T. (2003) Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads. Mol. Biol. Cell 14, 2809-2817 (Pubitemid 36871523)
39. Shen, R., Chen, M., Wang, Y.J., Kaneki, H., Xing, L., O'keefe, R.J., and Chen, D. (2006) Smad6 interacts with Runx2 and mediates Smad ubiquitin regulatory factor 1-induced Runx2 degradation. J. Biol. Chem. 281, 3569-3576 (Pubitemid 43845974)
40. Yamashita, M., Ying, S.X., Zhang, G.M., Li, C., Cheng, S.Y., Deng, C.X., and Zhang, Y.E. (2005) Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell 121, 101-113
41. Horiki, M., Imamura, T., Okamoto, M., Hayashi, M., Murai, J., Myoui, A., Ochi, T., Miyazono, K., Yoshikawa, H., and Tsumaki, N. (2004) Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia. J. Cell Biol 165, 433-445 (Pubitemid 38649917)
42. Yoshida, Y., Tanaka, S., Umemori, H., Minowa, O., Usui, M., Ikematsu, N., Hosoda, E., Imamura, T., Kuno, J., Yamashita, T., Miyazono, K., Noda, M., Noda, T., and Yamamoto, T. (2000) Negative regulation of BMP/Smad signaling by Tob in osteoblasts. Cell 103, 1085-1097 (Pubitemid 32037395)
43. Zamurovic, N., Cappellen, D., Rohner, D., and Susa, M. (2004) Coordinated activation of notch, Wnt, and transforming growth factor-beta signaling pathways in bone morphogenic protein 2-induced osteogenesis. Notch target gene Hey1 inhibits mineralization and Runx2 transcriptional activity. J. Biol. Chem. 279, 37704-37715 (Pubitemid 39195484)
44. Liu, T., Gao, Y., Sakamoto, K., Minamizato, T., Furukawa, K., Tsukazaki, T., Shibata, Y., Bessho, K., Komori, T., and Yamaguchi, A. (2007) BMP-2 promotes differentiation of osteoblasts and chondroblasts in Runx2-deficient cell lines. J. Cell. Physiol. 211, 728-735 (Pubitemid 46683041)
45. Minamizato, T., Sakamoto, K., Liu, T., Kokubo, H., Katsube, K., Perbal, B., Nakamura, S., and Yamaguchi, A. (2007) CCN3/NOV inhibits BMP-2-induced osteoblast differentiation by interacting with BMP and Notch signaling pathways. Biochem. Biophys. Res. Commun. 354, 567-573 (Pubitemid 46161361)
46. Leong, G.M., Subramaniam, N., Figueroa, J., Flanagan, J.L., Hayman, M.J., Eisman, J.A., and Kouzmenko, A.P. (2001) Ski-interacting protein interacts with Smad proteins to augment transforming growth factor-beta-dependent transcription. J. Biol. Chem. 276, 18243-18248
47. Leong, G.M., Subramaniam, N., Issa, L.L., Barry, J.B., Kino, T., Driggers, P.H., Hayman, M.J., Eisman, J.A., and Gardiner, E.M. (2004) Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300. Biochem. Biophys. Res. Commun. 315, 1070-1076 (Pubitemid 38249412)
48. Kokura, K., Kim, H., Shinagawa, T., Khan, M.M., Nomura, T., and Ishii, S. (2003) The Ski-binding protein C184M negatively regulates tumor growth factor-beta signaling by sequestering the Smad proteins in the cytoplasm. J. Biol. Chem. 278, 20133-20139 (Pubitemid 36799208)
49. Takeda, M., Mizuide, M., Oka, M., Watabe, T., Inoue, H., Suzuki, H., Fujita, T., Imamura, T., Miyazono, K., and Miyazawa, K. (2004) Interaction with Smad4 is indispensable for suppression of BMP signaling by c-Ski. Mol. Biol. Cell 15, 963-972 (Pubitemid 38316207)
50. Miyazono, K., Maeda, S., and Imamura, T. (2004) Coordinate regulation of cell growth and differentiation by TGF-beta superfamily and Runx proteins. Oncogene 23, 4232-4237 (Pubitemid 38758589)
51. ten Dijke, P., Miyazono, K., and Heldin, C.H. (2000) Signaling inputs converge on nuclear effectors in TGF-beta signaling. Trends Biochem. Sci. 25, 64-70 (Pubitemid 30100368)
52. Centrella, M., Horowitz, M.C., Wozney, J.M., and McCarthy, T.L. (1994) Transforming growth factor-beta gene family members and bone. Endocr. Rev. 15, 27-39
53. Sowa, H., Kaji, H., Yamaguchi, T., Sugimoto, T., and Chihara, K. (2002) Smad3 promotes alkaline phosphatase activity and mineralization of osteoblastic MC3T3-E1 cells. J. Bone Miner. Res. 17, 1190-1199 (Pubitemid 34680495)
54. Maeda, S., Hayashi, M., Komiya, S., Imamura, T., and Miyazono, K. (2004) Endogenous TGF-beta signaling suppresses maturation of osteoblastic mesenchymal cells. EMBO J. 23, 552-563 (Pubitemid 38282387)
55. de Gorter, D.J., van Dinther, M., Korchynskyi, O., and ten Dijke, P. (2011) Biphasic effects of transforming growth factor I-2 on bone morphogenetic protein-induced osteoblast differentiation. J. Bone Miner. Res. 26, 1178-1187
56. Kang, J.S., Alliston, T., Delston, R., and Derynck, R. (2005) Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3. EMBO J. 24, 2543-2555 (Pubitemid 41076311)
57. Tang, Y., Wu, X., Lei, W., Pang, L., Wan, C., Shi, Z., Zhao, L., Nagy, T.R., Peng, X., Hu, J., Feng, X., Van Hul, W., Wan, M., and Cao, X. (2009) TGFbeta1-induced migration of bone mesenchymal stem cells couples bone resorption with formation. Nat. Med. 15, 757-765
58. Qiu, T., Wu, X., Zhang, F., Clemens, T.L., Wan, M., and Cao, X. (2010) TGF-beta type II receptor phosphorylates PTH receptor to integrate bone remodelling signalling. Nat. Cell Biol. 12, 224-234
59. Foster, J.W., Dominguez-Steglich, M.A., Guioli, S., Kwok, C., Weller, P.A., Stevanovic, M., Weissenbach, J., Mansour, S., Young, I.D., and Goodfellow, P.N. (1994) Campomelic dysplasia and autosomal sex reversal caused by mutations in an SRY-related gene. Nature 372, 525-530 (Pubitemid 24368528)
60. Wagner, T., Wirth, J., Meyer, J., Zabel, B., Held, M., Zimmer, J., Pasantes, J., Bricarelli, F.D., Keutel, J., Hustert, E., Wolf, U., Tommerup, N., Schempp, W., and Scherer, G. (1994) Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell 79, 1111-1120
61. Akiyama, H., Chaboissier, M.C., Martin, J.F., Schedl, A., and de Crombrugghe, B. (2002) The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev. 16, 2813-2828 (Pubitemid 35253149)
62. Takigawa, Y., Hata, K., Muramatsu, S., Amano, K., Ono, K., Wakabayashi, M., Matsuda, A., Takada, K., Nishimura, R., and Yoneda, T. (2010) The transcription factor Znf219 regulates chondrocyte differentiation by assembling a transcription factory with Sox9. J. Cell Sci. 123, 3780-3788
63. Smits, P., Dy, P., Mitra, S., and Lefebvre, V. (2004) Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate. J. Cell Biol 164, 747-758 (Pubitemid 38282958)
64. Saito, T., Ikeda, T., Nakamura, K., Chung, U.I., and Kawaguchi, H. (2007) S100A1 and S100B, transcriptional targets of SOX trio, inhibit terminal differentiation of chondrocytes. EMBO Rep. 8, 504-509 (Pubitemid 46696522)
65. Muramatsu, S., Wakabayashi, M., Ohno, T., Amano, K., Ooishi, R., Sugahara, T., Shiojiri, S., Tashiro, K., Suzuki, Y., Nishimura, R., Kuhara, S., Sugano, S., Yoneda, T., and Matsuda, A. (2007) Functional gene screening system identified TRPV4 as a regulator of chondrogenic differentiation. J. Biol. Chem. 282, 32158-32167 (Pubitemid 350106454)
66. Rock, M.J., Prenen, J., Funari, V.A., Funari, T.L., Merriman, B., Nelson, S.F., Lachman, R.S., Wilcox, W.R., Reyno, S., Quadrelli, R., Vaglio, A., Owsianik, G., Janssens, A., Voets, T., Ikegawa, S., Nagai, T., Rimoin, D.L., Nilius, B., and Cohn, D.H. (2008) Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia. Nat. Genet. 40, 999-1003
67. Nishimura, G., Dai, J., Lausch, E., Unger, S., Megarbané, A., Kitoh, H., Kim, O.H., Cho, T.J., Bedeschi, F., Benedicenti, F., Mendoza-Londono, R., Silengo, M., Schmidt-Rimpler, M., Spranger, J., Zabel, B., Ikegawa, S., and Superti-Furga, A. (2010) Spondylo-epiphyseal dysplasia, Maroteaux type (pseudo-Morquio syndrome type 2), and parastremmatic dysplasia are caused by TRPV4 mutations. Am. J. Med. Genet. A 152A, 1443-1449
68. Hata, K., Nishimura, R., Muramatsu, S., Matsuda, A., Matsubara, T., Amano, K., Ikeda, F., Harley, V.R., and Yoneda, T. (2008) Paraspeckle protein p54nrb links Sox9-mediated transcription with RNA processing during chondrogenesis in mice. J. Clin. Invest. 118, 3098-3108
69. Amano, K., Hata, K., Muramatsu, S., Wakabayashi, M., Takigawa, Y., Ono, K., Nakanishi, M., Takashima, R., Kogo, M., Matsuda, A., Nishimura, R., and Yoneda, T. (2011) Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription. Mol. Biol. Cell 22, 1300-1311
70. Amano, K., Hata, K., Sugita, A., Takigawa, Y., Ono, K., Wakabayashi, M., Kogo, M., Nishimura, R., and Yoneda, T. (2009) Sox9 family members negatively regulate maturation and calcification of chondrocytes through up-regulation of parathyroid hormone-related protein. Mol. Biol. Cell 20, 4541-4551
71. Hattori, T., Müller, C., Gebhard, S., Bauer, E., Pausch, F., Schlund, B., Bösl, M.R., Hess, A., Surmann-Schmitt, C., von der Mark, H., de Crombrugghe, B., and von der Mark, K. (2010) SOX9 is a major negative regulator of cartilage vascularization, bone marrow formation and endochondral ossification. Development 137, 901-911
72. Yoshida, C.A., Yamamoto, H., Fujita, T., Furuichi, T., Ito, K., Inoue, K., Yamana, K., Zanma, A., Takada, K., Ito, Y., and Komori, T. (2004) Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev. 18, 952-963 (Pubitemid 38529663)
73. Shimoyama, A., Wada, M., Ikeda, F., Hata, K., Matsubara, T., Nifuji, A., Noda, M., Amano, K., Yamaguchi, A., Nishimura, R., and Yoneda, T. (2007) Ihh/Gli2 signaling promotes osteoblast differentiation by regulating Runx2 expression and function. Mol. Biol. Cell. 18, 2411-2418 (Pubitemid 47025707)
74. Amano, K., Ichida, F., Sugita, A., Hata, K., Wada, M., Takigawa, Y., Nakanishi, M., Kogo, M., Nishimura, R., and Yoneda, T. (2008) MSX2 stimulates chondrocyte maturation by controlling Ihh expression. J. Biol. Chem. 283, 29513-29521
75. Asada, R., Kanemoto, S., Kondo, S., Saito, A., and Imaizumi, K. (2011) The signalling from endoplasmic reticulum-resident bZIP transcription factors involved in diverse cellular physiology. J. Biochem. 149, 507-518
76. Murakami, T., Saito, A., Hino, S., Kondo, S., Kanemoto, S., Chihara, K., Sekiya, H., Tsumagari, K., Ochiai, K., Yoshinaga, K., Saitoh, M., Nishimura, R., Yoneda, T., Kou, I., Furuichi, T., Ikegawa, S., Ikawa, M., Okabe, M., Wanaka, A., and Imaizumi, K. (2009) Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation. Nat. Cell Biol. 11, 1205-1211
77. Saito, A., Hino, S., Murakami, T., Kanemoto, S., Kondo, S., Saitoh, M., Nishimura, R., Yoneda, T., Furuichi, T., Ikegawa, S., Ikawa, M., Okabe, M., and Imaizumi, K. (2009) Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. Nat. Cell Biol. 11, 1197-1204
78. Murakami, T., Hino, S., Nishimura, R., Yoneda, T., Wanaka, A., and Imaizumi, K. (2011) Distinct mechanisms are responsible for osteopenia and growth retardation in OASIS-deficient mice. Bone 48, 514-523