Smad signaling in skeletal development and regeneration

Cytokine and Growth Factor Reviews

Volumn 20, Issue 5-6, 2009, Pages 379-388

  Song, Buer ^a   Estrada, Kristine D ^a   Lyons, Karen M ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

BMP; in vivo; non canonical signaling; regeneration; Skeletal development; Smad; TGFbeta

Indexed keywords

BONE MORPHOGENETIC PROTEIN; CELL SURFACE RECEPTOR; CYTOPLASM PROTEIN; FIBROBLAST GROWTH FACTOR; GROWTH FACTOR; MITOGEN ACTIVATED PROTEIN KINASE; PARATHYROID HORMONE RELATED PROTEIN; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SMAD PROTEIN; SMAD1 PROTEIN; SMAD2 PROTEIN; SMAD3 PROTEIN; SMAD4 PROTEIN; SMAD5 PROTEIN; SMAD6 PROTEIN; SMAD7 PROTEIN; SMAD8 PROTEIN; SONIC HEDGEHOG PROTEIN; TRANSCRIPTION FACTOR RUNX2; TRANSFORMING GROWTH FACTOR BETA; WNT PROTEIN;

ARTICLE; BONE DEVELOPMENT; BONE REGENERATION; CELL NUCLEUS; CHONDROGENESIS; CYTOPLASM; GENE ACTIVATION; GENE REPRESSION; GENETIC TRANSCRIPTION; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN INTERACTION; PROTEIN LOCALIZATION; PROTEIN TRANSPORT; RECEPTOR BINDING; SEQUENCE HOMOLOGY; SIGNAL TRANSDUCTION;

ANIMALS; BONE DEVELOPMENT; BONE REGENERATION; CHONDROGENESIS; HUMANS; MODELS, BIOLOGICAL; OSTEOGENESIS; SIGNAL TRANSDUCTION; SMAD PROTEINS; TGF-BETA SUPERFAMILY PROTEINS;

EID: 70649113726     PISSN: 13596101     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2009.10.010     Document Type: Article

References (126)

1. Urist M.R., Dowell T.A., Hay P.H., and Strates B.S. Inductive substrates for bone formation. Clin Orthop Relat Res 59 (1968) 59-96
2. Anzano M.A., Roberts A.B., Smith J.M., Sporn M.B., and De Larco J.E. Sarcoma growth factor from conditioned medium of virally transformed cells is composed of both type alpha and type beta transforming growth factors. Proc Natl Acad Sci USA 80 20 (1983) 6264-6268
3. Roberts A.B., Frolik C.A., Anzano M.A., and Sporn M.B. Transforming growth factors from neoplastic and nonneoplastic tissues. Fed Proc 42 9 (1983) 2621-2626
4. Burt D.W., and Law A.S. Evolution of the transforming growth factor-beta superfamily. Prog Growth Factor Res 5 1 (1994) 99-118
5. Ripamonti U., Crooks J., Matsaba T., and Tasker J. Induction of endochondral bone formation by recombinant human transforming growth factor-beta2 in the baboon (Papio ursinus). Growth Factors 17 4 (2000) 269-285
6. Ripamonti U., Ramoshebi L.N., Teare J., Renton L., and Ferretti C. The induction of endochondral bone formation by transforming growth factor-beta(3): experimental studies in the non-human primate Papio ursinus. J Cell Mol Med 12 3 (2008) 1029-1048
7. Sekelsky J.J., Newfeld S.J., Raftery L.A., Chartoff E.H., and Gelbart W.M. Genetic characterization and cloning of mothers against dpp, a gene required for decapentaplegic function in Drosophila melanogaster. Genetics 139 3 (1995) 1347-1358
8. Savage C., Das P., Finelli A.L., Townsend S.R., Sun C.Y., Baird S.E., et al. Caenorhabditis elegans genes sma-2, sma-3, and sma-4 define a conserved family of transforming growth factor beta pathway components. Proc Natl Acad Sci USA 93 2 (1996) 790-794
9. Massague J., Seoane J., and Wotton D. Smad transcription factors. Genes Dev 19 23 (2005) 2783-2810
10. Wu M.Y., and Hill C.S. TGF-beta superfamily signaling in embryonic development and homeostasis. Dev Cell 16 3 (2009) 329-343
11. Zhang J., Tan X., Li W., Wang Y., Wang J., Cheng X., et al. Smad4 is required for the normal organization of the cartilage growth plate. Dev Biol 284 2 (2005) 311-322
12. Retting K.N., Song B., Yoon B.S., and Lyons K.M. BMP canonical Smad signaling through Smad1 and Smad5 is required for endochondral bone formation. Development 136 7 (2009) 1093-1104
13. Provot S., and Schipani E. Molecular mechanisms of endochondral bone development. Biochem Biophys Res Commun 328 3 (2005) 658-665
14. Kitisin K., Saha T., Blake T., Golestaneh N., Deng M., Kim C., et al. TGF-beta signaling in development. Sci STKE 2007 399 (2007) pcm1
15. Cao X., and Chen D. The BMP signaling and in vivo bone formation. Gene 357 1 (2005) 1-8
16. Zhao G.Q. Consequences of knocking out BMP signaling in the mouse. Genesis 35 1 (2003) 43-56
17. Moustakas A., and Heldin C.H. Non-Smad TGF-beta signals. J Cell Sci 118 Pt 16 (2005) 3573-3584
18. Rahimi R.A., and Leof E.B. TGF-beta signaling: a tale of two responses. J Cell Biochem 102 3 (2007) 593-608
19. Tremblay K.D., Dunn N.R., and Robertson E.J. Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation. Development 128 18 (2001) 3609-3621
20. Nomura M., and Li E. Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature 393 6687 (1998) 786-790
21. Waldrip W.R., Bikoff E.K., Hoodless P.A., Wrana J.L., and Robertson E.J. Smad2 signaling in extraembryonic tissues determines anterior-posterior polarity of the early mouse embryo. Cell 92 6 (1998) 797-808
22. Weinstein M., Yang X., Li C., Xu X., Gotay J., and Deng C.X. Failure of egg cylinder elongation and mesoderm induction in mouse embryos lacking the tumor suppressor smad2. Proc Natl Acad Sci USA 95 16 (1998) 9378-9383
23. Heyer J., Escalante-Alcalde D., Lia M., Boettinger E., Edelmann W., Stewart C.L., et al. Postgastrulation Smad2-deficient embryos show defects in embryo turning and anterior morphogenesis. Proc Natl Acad Sci USA 96 22 (1999) 12595-12600
24. Tremblay K.D., Hoodless P.A., Bikoff E.K., and Robertson E.J. Formation of the definitive endoderm in mouse is a Smad2-dependent process. Development 127 14 (2000) 3079-3090
25. Zhu Y., Richardson J.A., Parada L.F., and Graff J.M. Smad3 mutant mice develop metastatic colorectal cancer. Cell 94 6 (1998) 703-714
26. Datto M.B., Frederick J.P., Pan L., Borton A.J., Zhuang Y., and Wang X.F. Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction. Mol Cell Biol 19 4 (1999) 2495-2504
27. Yang X., Letterio J.J., Lechleider R.J., Chen L., Hayman R., Gu H., et al. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-beta. EMBO J 18 5 (1999) 1280-1291
28. Yang X., Chen L., Xu X., Li C., Huang C., and Deng C.X. TGF-beta/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage. J Cell Biol 153 1 (2001) 35-46
29. Li T.F., Darowish M., Zuscik M.J., Chen D., Schwarz E.M., Rosier R.N., et al. Smad3-deficient chondrocytes have enhanced BMP signaling and accelerated differentiation. J Bone Miner Res 21 1 (2006) 4-16
30. Sirard C., de la Pompa J.L., Elia A., Itie A., Mirtsos C., Cheung A., et al. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev 12 1 (1998) 107-119
31. Yang X., Li C., Xu X., and Deng C. The tumor suppressor SMAD4/DPC4 is essential for epiblast proliferation and mesoderm induction in mice. Proc Natl Acad Sci USA 95 7 (1998) 3667-3672
32. Tan X., Weng T., Zhang J., Wang J., Li W., Wan H., et al. Smad4 is required for maintaining normal murine postnatal bone homeostasis. J Cell Sci 120 Pt 13 (2007) 2162-2170
33. Yang X., Castilla L.H., Xu X., Li C., Gotay J., Weinstein M., et al. Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development 126 8 (1999) 1571-1580
34. Galvin K.M., Donovan M.J., Lynch C.A., Meyer R.I., Paul R.J., Lorenz J.N., et al. A role for smad6 in development and homeostasis of the cardiovascular system. Nat Genet 24 2 (2000) 171-174
35. Horiki M., Imamura T., Okamoto M., Hayashi M., Murai J., Myoui A., et al. Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia. J Cell Biol 165 3 (2004) 433-445
36. Chen Q., Chen H., Zheng D., Kuang C., Fang H., Zou B., et al. Smad7 is required for the development and function of the heart. J Biol Chem 284 1 (2009) 292-300
37. Li R., Rosendahl A., Brodin G., Cheng A.M., Ahgren A., Sundquist C., et al. Deletion of exon I of SMAD7 in mice results in altered B cell responses. J Immunol 176 11 (2006) 6777-6784
38. Hamzavi J., Ehnert S., Godoy P., Ciuclan L., Weng H., Mertens P.R., et al. Disruption of the Smad7 gene enhances CCI4-dependent liver damage and fibrogenesis in mice. J Cell Mol Med 12 5B (2008) 2130-2144
39. Chung A.C., Huang X.R., Zhou L., Heuchel R., Lai K.N., and Lan H.Y. Disruption of the Smad7 gene promotes renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) in mice. Nephrol Dial Transplant 24 5 (2009) 1443-1454
40. Iwai T., Murai J., Yoshikawa H., and Tsumaki N. Smad7 Inhibits chondrocyte differentiation at multiple steps during endochondral bone formation and down-regulates p38 MAPK pathways. J Biol Chem 283 40 (2008) 27154-27164
41. Sakou T., Onishi T., Yamamoto T., Nagamine T., Sampath T., and Ten Dijke P. Localization of Smads, the TGF-beta family intracellular signaling components during endochondral ossification. J Bone Miner Res 14 7 (1999) 1145-1152
42. Orvis G.D., Jamin S.P., Kwan K.M., Mishina Y., Kaartinen V.M., Huang S., et al. Functional redundancy of TGF-beta family type I receptors and receptor-Smads in mediating anti-Mullerian hormone-induced Mullerian duct regression in the mouse. Biol Reprod 78 6 (2008) 994-1001
43. Pangas S.A., Li X., Umans L., Zwijsen A., Huylebroeck D., Gutierrez C., et al. Conditional deletion of Smad1 and Smad5 in somatic cells of male and female gonads leads to metastatic tumor development in mice. Mol Cell Biol 28 1 (2008) 248-257
44. Yoon B.S., Ovchinnikov D.A., Yoshii I., Mishina Y., Behringer R.R., and Lyons K.M. Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo. Proc Natl Acad Sci USA 102 14 (2005) 5062-5067
45. Yoon B.S., and Lyons K.M. Multiple functions of BMPs in chondrogenesis. J Cell Biochem 93 1 (2004) 93-103
46. Pan Q., Yu Y., Chen Q., Li C., Wu H., Wan Y., et al. Sox9, a key transcription factor of bone morphogenetic protein-2-induced chondrogenesis, is activated through BMP pathway and a CCAAT box in the proximal promoter. J Cell Physiol 217 1 (2008) 228-241
47. Pan Q., Wu Y., Lin T., Yao H., Yang Z., Gao G., et al. Bone morphogenetic protein-2 induces chromatin remodeling and modification at the proximal promoter of Sox9 gene. Biochem Biophys Res Commun 379 2 (2009) 356-361
48. Seki K., and Hata A. Indian hedgehog gene is a target of the bone morphogenetic protein signaling pathway. J Biol Chem 279 18 (2004) 18544-18549
49. Hatakeyama Y., Nguyen J., Wang X., Nuckolls G.H., and Shum L. Smad signaling in mesenchymal and chondroprogenitor cells. J Bone Joint Surg Am 85-A Suppl. 3 (2003) 13-18
50. Drissi M.H., Li X., Sheu T.J., Zuscik M.J., Schwarz E.M., Puzas J.E., et al. Runx2/Cbfa1 stimulation by retinoic acid is potentiated by BMP2 signaling through interaction with Smad1 on the collagen X promoter in chondrocytes. J Cell Biochem 90 6 (2003) 1287-1298
51. Lee K.S., Kim H.J., Li Q.L., Chi X.Z., Ueta C., Komori T., et al. 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 23 (2000) 8783-8792
52. Kim D.W., and Lassar A.B. Smad-dependent recruitment of a histone deacetylase/Sin3A complex modulates the bone morphogenetic protein-dependent transcriptional repressor activity of Nkx3.2. Mol Cell Biol 23 23 (2003) 8704-8717
53. Haag J., and Aigner T. Identification of calponin 3 as a novel Smad-binding modulator of BMP signaling expressed in cartilage. Exp Cell Res 313 16 (2007) 3386-3394
54. Bech-Otschir D., Seeger M., and Dubiel W. The COP9 signalosome: at the interface between signal transduction and ubiquitin-dependent proteolysis. J Cell Sci 115 Pt 3 (2002) 467-473
55. Haag J., and Aigner T. Jun activation domain-binding protein 1 binds Smad5 and inhibits bone morphogenetic protein signaling. Arthritis Rheum 54 12 (2006) 3878-3884
56. Serra R., Johnson M., Filvaroff E.H., LaBorde J., Sheehan D.M., Derynck R., et al. Expression of a truncated, kinase-defective TGF-beta type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis. J Cell Biol 139 2 (1997) 541-552
57. Baffi M.O., Slattery E., Sohn P., Moses H.L., Chytil A., and Serra R. Conditional deletion of the TGF-beta type II receptor in Col2a expressing cells results in defects in the axial skeleton without alterations in chondrocyte differentiation or embryonic development of long bones. Dev Biol 276 1 (2004) 124-142
58. Seo H.S., and Serra R. Deletion of Tgfbr2 in Prx1-cre expressing mesenchyme results in defects in development of the long bones and joints. Dev Biol 310 2 (2007) 304-316
59. Furumatsu T., Tsuda M., Taniguchi N., Tajima Y., and Asahara H. Smad3 induces chondrogenesis through the activation of SOX9 via CREB-binding protein/p300 recruitment. J Biol Chem 280 9 (2005) 8343-8350
60. Furumatsu T., Ozaki T., and Asahara H. Smad3 activates the Sox9-dependent transcription on chromatin. Int J Biochem Cell Biol 41 5 (2009) 1198-1204
61. Alvarez J., and Serra R. Unique and redundant roles of Smad3 in TGF-beta-mediated regulation of long bone development in organ culture. Dev Dyn 230 4 (2004) 685-699
62. Brown K.A., Pietenpol J.A., and Moses H.L. A tale of two proteins: differential roles and regulation of Smad2 and Smad3 in TGF-beta signaling. J Cell Biochem 101 1 (2007) 9-33
63. Davis B.N., Hilyard A.C., Lagna G., and Hata A. SMAD proteins control DROSHA-mediated microRNA maturation. Nature 454 7200 (2008) 56-61
64. Itoh T., Nozawa Y., and Akao Y. MicroRNA-141 and -200a are involved in bone morphogenetic protein-2-induced mouse Pre-osteoblast differentiation by targeting distal-less homeobox 5. J Biol Chem (2009)
65. Lin E.A., Kong L., Bai X.H., Luan Y., and Liu C.J. miR-199a, a bone morphogenic protein 2-responsive MicroRNA, regulates chondrogenesis via direct targeting to Smad1. J Biol Chem 284 17 (2009) 11326-11335
66. Otto F., Thornell A.P., Crompton T., Denzel A., Gilmour K.C., Rosewell I.R., et al. Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell 89 5 (1997) 765-771
67. Komori T., Yagi H., Nomura S., Yamaguchi A., Sasaki K., Deguchi K., et al. Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89 5 (1997) 755-764
68. Zhang Y.W., Yasui N., Ito K., Huang G., Fujii M., Hanai J., et al. A RUNX2/PEBP2alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia. Proc Natl Acad Sci USA 97 19 (2000) 10549-10554
69. Afzal F., Pratap J., Ito K., Ito Y., Stein J.L., van Wijnen A.J., et al. Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription. J Cell Physiol 204 1 (2005) 63-72
70. Javed A., Afzal F., Bae J.S., Gutierrez S., Zaidi K., Pratap J., et al. Specific residues of RUNX2 are obligatory for formation of BMP2-induced RUNX2-SMAD complex to promote osteoblast differentiation. Cells Tissues Organs 189 1-4 (2009) 133-137
71. Wan M., Shi X., Feng X., and Cao X. Transcriptional mechanisms of bone morphogenetic protein-induced osteoprotegrin gene expression. J Biol Chem 276 13 (2001) 10119-10125
72. Nakashima K., Zhou X., Kunkel G., Zhang Z., Deng J.M., Behringer R.R., et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108 1 (2002) 17-29
73. Matsubara T., Kida K., Yamaguchi A., Hata K., Ichida F., Meguro H., et al. BMP2 regulates Osterix through Msx2 and Runx2 during osteoblast differentiation. J Biol Chem 283 43 (2008) 29119-29125
74. Brugger S.M., Merrill A.E., Torres-Vazquez J., Wu N., Ting M.C., Cho J.Y., et al. A phylogenetically conserved cis-regulatory module in the Msx2 promoter is sufficient for BMP-dependent transcription in murine and Drosophila embryos. Development 131 20 (2004) 5153-5165
75. Ryoo H.M., Lee M.H., and Kim Y.J. Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene 366 1 (2006) 51-57
76. Shi X., Bai S., Li L., and Cao X. Hoxa-9 represses transforming growth factor-beta-induced osteopontin gene transcription. J Biol Chem 276 1 (2001) 850-855
77. Kang J.S., Alliston T., Delston R., and Derynck R. Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3. EMBO J 24 14 (2005) 2543-2555
78. Wu X., Shi W., and Cao X. Multiplicity of BMP signaling in skeletal development. Ann NY Acad Sci 1116 (2007) 29-49
79. Ai-Aql Z.S., Alagl A.S., Graves D.T., Gerstenfeld L.C., and Einhorn T.A. Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis. J Dent Res 87 2 (2008) 107-118
80. Ripamonti U., Herbst N.N., and Ramoshebi L.N. Bone morphogenetic proteins in craniofacial and periodontal tissue engineering: experimental studies in the non-human primate Papio ursinus. Cytokine Growth Factor Rev 16 3 (2005) 357-368
81. Dimitriou R., Tsiridis E., and Giannoudis P.V. Current concepts of molecular aspects of bone healing. Injury 36 12 (2005) 1392-1404
82. Tsuji K., Bandyopadhyay A., Harfe B.D., Cox K., Kakar S., Gerstenfeld L., et al. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet 38 12 (2006) 1424-1429
83. Yu Y., Yang J.L., Chapman-Sheath P.J., and Walsh W.R. TGF-beta, BMPS, and their signal transducing mediators, Smads, in rat fracture healing. J Biomed Mater Res 60 3 (2002) 392-397
84. Verrecchia F., Chu M.L., and Mauviel A. Identification of novel TGF-beta/Smad gene targets in dermal fibroblasts using a combined cDNA microarray/promoter transactivation approach. J Biol Chem 276 20 (2001) 17058-17062
85. Schiller M., Javelaud D., and Mauviel A. TGF-beta-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing. J Dermatol Sci 35 2 (2004) 83-92
86. Blom A.B., van der Kraan P.M., and van den Berg W.B. Cytokine targeting in osteoarthritis. Curr Drug Targets 8 2 (2007) 283-292
87. Hayashi H., Abdollah S., Qiu Y., Cai J., Xu Y.Y., Grinnell B.W., et al. The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell 89 7 (1997) 1165-1173
88. Imamura T., Takase M., Nishihara A., Oeda E., Hanai J., Kawabata M., et al. Smad6 inhibits signalling by the TGF-beta superfamily. Nature 389 6651 (1997) 622-626
89. Nakao A., Afrakhte M., Moren A., Nakayama T., Christian J.L., Heuchel R., et al. Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 389 6651 (1997) 631-635
90. Hata A., Lagna G., Massague J., and Hemmati-Brivanlou A. Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. Genes Dev 12 2 (1998) 186-197
91. Kavsak P., Rasmussen R.K., Causing C.G., Bonni S., Zhu H., Thomsen G.H., et al. Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol Cell 6 6 (2000) 1365-1375
92. Murakami G., Watabe T., Takaoka K., Miyazono K., and Imamura T. Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads. Mol Biol Cell 14 7 (2003) 2809-2817
93. Suzuki C., Murakami G., Fukuchi M., Shimanuki T., Shikauchi Y., Imamura T., et al. Smurf1 regulates the inhibitory activity of Smad7 by targeting Smad7 to the plasma membrane. J Biol Chem 277 42 (2002) 39919-39925
94. Moren A., Imamura T., Miyazono K., Heldin C.H., and Moustakas A. Degradation of the tumor suppressor Smad4 by WW and HECT domain ubiquitin ligases. J Biol Chem 280 23 (2005) 22115-22123
95. Koinuma D., Shinozaki M., Komuro A., Goto K., Saitoh M., Hanyu A., et al. Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J 22 24 (2003) 6458-6470
96. Li X., Ionescu A.M., Schwarz E.M., Zhang X., Drissi H., Puzas J.E., et al. Smad6 is induced by BMP-2 and modulates chondrocyte differentiation. J Orthop Res 21 5 (2003) 908-913
97. Valcourt U., Gouttenoire J., Moustakas A., Herbage D., and Mallein-Gerin F. Functions of transforming growth factor-beta family type I receptors and Smad proteins in the hypertrophic maturation and osteoblastic differentiation of chondrocytes. J Biol Chem 277 37 (2002) 33545-33558
98. Kronenberg H.M. Developmental regulation of the growth plate. Nature 423 6937 (2003) 332-336
99. Liu F., Massague J., and Ruiz i Altaba A. Carboxy-terminally truncated Gli3 proteins associate with Smads. Nat Genet 20 4 (1998) 325-326
100. Alvarez J., Sohn P., Zeng X., Doetschman T., Robbins D.J., and Serra R. TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Development 129 8 (2002) 1913-1924
101. Dennler S., Andre J., Alexaki I., Li A., Magnaldo T., ten Dijke P., et al. Induction of sonic hedgehog mediators by transforming growth factor-beta: Smad3-dependent activation of Gli2 and Gli1 expression in vitro and in vivo. Cancer Res 67 14 (2007) 6981-6986
102. Ornitz D.M. FGF signaling in the developing endochondral skeleton. Cytokine Growth Factor Rev 16 2 (2005) 205-213
103. Yoon B.S., Pogue R., Ovchinnikov D.A., Yoshii I., Mishina Y., Behringer R.R., et al. BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways. Development 133 23 (2006) 4667-4678
104. Kretzschmar M., Doody J., Timokhina I., and Massague J. A mechanism of repression of TGFbeta/Smad signaling by oncogenic Ras. Genes Dev 13 7 (1999) 804-816
105. Pera E.M., Ikeda A., Eivers E., and De Robertis E.M. Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. Genes Dev 17 24 (2003) 3023-3028
106. Rodriguez-Esteban C., Capdevila J., Kawakami Y., and Izpisua Belmonte J.C. Wnt signaling and PKA control Nodal expression and left-right determination in the chick embryo. Development 128 16 (2001) 3189-3195
107. Jin E.J., Lee S.Y., Choi Y.A., Jung J.C., Bang O.S., and Kang S.S. BMP-2-enhanced chondrogenesis involves p38 MAPK-mediated down-regulation of Wnt-7a pathway. Mol Cells 22 3 (2006) 353-359
108. Luo Q., Kang Q., Si W., Jiang W., Park J.K., Peng Y., et al. Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells. J Biol Chem 279 53 (2004) 55958-55968
109. Abreu J.G., Ketpura N.I., Reversade B., and De Robertis E.M. Connective-tissue growth factor (CTGF) modulates cell signalling by BMP and TGF-beta. Nat Cell Biol 4 8 (2002) 599-604
110. Guo X., and Wang X.F. Signaling cross-talk between TGF-beta/BMP and other pathways. Cell Res 19 1 (2009) 71-88
111. Labbe E., Letamendia A., and Attisano L. Association of Smads with lymphoid enhancer binding factor 1/T cell-specific factor mediates cooperative signaling by the transforming growth factor-beta and Wnt pathways. Proc Natl Acad Sci USA 97 15 (2000) 8358-8363
112. Nishita M., Hashimoto M.K., Ogata S., Laurent M.N., Ueno N., Shibuya H., et al. Interaction between Wnt and TGF-beta signalling pathways during formation of Spemann's organizer. Nature 403 6771 (2000) 781-785
113. Laurent M.N., and Cho K.W. Bone morphogenetic protein antagonism of Spemann's organizer is independent of Wnt signaling. Dev Biol 206 2 (1999) 157-162
114. Theil T., Aydin S., Koch S., Grotewold L., and Ruther U. Wnt and Bmp signalling cooperatively regulate graded Emx2 expression in the dorsal telencephalon. Development 129 13 (2002) 3045-3054
115. Hussein S.M., Duff E.K., and Sirard C. Smad4 and beta-catenin co-activators functionally interact with lymphoid-enhancing factor to regulate graded expression of Msx2. J Biol Chem 278 49 (2003) 48805-48814
116. Willert J., Epping M., Pollack J.R., Brown P.O., and Nusse R. A transcriptional response to Wnt protein in human embryonic carcinoma cells. BMC Dev Biol 2 (2002) p8
117. Fuentealba L.C., Eivers E., Ikeda A., Hurtado C., Kuroda H., Pera E.M., et al. Integrating patterning signals: Wnt/GSK3 regulates the duration of the BMP/Smad1 signal. Cell 131 5 (2007) 980-993
118. Sapkota G., Alarcon C., Spagnoli F.M., Brivanlou A.H., and Massague J. Balancing BMP signaling through integrated inputs into the Smad1 linker. Mol Cell 25 3 (2007) 441-454
119. Furuhashi M., Yagi K., Yamamoto H., Furukawa Y., Shimada S., Nakamura Y., et al. Axin facilitates Smad3 activation in the transforming growth factor beta signaling pathway. Mol Cell Biol 21 15 (2001) 5132-5141
120. Guo X., Ramirez A., Waddell D.S., Li Z., Liu X., and Wang X.F. Axin and GSK3-control Smad3 protein stability and modulate TGF-signaling. Genes Dev 22 1 (2008) 106-120
121. Jian H., Shen X., Liu I., Semenov M., He X., and Wang X.F. Smad3-dependent nuclear translocation of beta-catenin is required for TGF-beta1-induced proliferation of bone marrow-derived adult human mesenchymal stem cells. Genes Dev 20 6 (2006) 666-674
122. Liu Z., Tang Y., Qiu T., Cao X., and Clemens T.L. A dishevelled-1/Smad1 interaction couples WNT and bone morphogenetic protein signaling pathways in uncommitted bone marrow stromal cells. J Biol Chem 281 25 (2006) 17156-17163
123. Ramesh S., Wildey G.M., and Howe P.H. Transforming growth factor beta (TGFbeta)-induced apoptosis: the rise & fall of Bim. Cell Cycle 8 1 (2009) 11-17
124. Ghosh-Choudhury N., Abboud S.L., Nishimura R., Celeste A., Mahimainathan L., and Choudhury G.G. 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 36 (2002) 33361-33368
125. Kim S.I., Kwak J.H., Na H.J., Kim J.K., Ding Y., and Choi M.E. TGF-{beta}1 activates TAK1 via TAB1-mediated autophosphorylation, independent of TGF-{beta} receptor kinase activity in mesangial cells. J Biol Chem (2009)
126. Shim J.H., Greenblatt M.B., Xie M., Schneider M.D., Zou W., Zhai B., et al. TAK1 is an essential regulator of BMP signalling in cartilage. EMBO J 28 14 (2009) 2028-2041