BMP Signaling in the Cartilage Growth Plate

Current Topics in Developmental Biology

Volumn 76, Issue , 2006, Pages 1-48

  Pogue, Robert ^a   Lyons, Karen ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BONE MORPHOGENETIC PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL; BIOLOGICAL MODEL; CARTILAGE CELL; CELL DIFFERENTIATION; CHONDROGENESIS; CYTOLOGY; GROWTH PLATE; GROWTH, DEVELOPMENT AND AGING; HUMAN; MOUSE; OSTEOARTHRITIS; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; BONE MORPHOGENETIC PROTEINS; CELL DIFFERENTIATION; CHONDROCYTES; CHONDROGENESIS; GROWTH PLATE; HUMANS; MICE; MODELS, BIOLOGICAL; OSTEOARTHRITIS; SIGNAL TRANSDUCTION; TRANSFORMING GROWTH FACTOR BETA;

EID: 33751069567     PISSN: 00702153     EISSN: None     Source Type: Book Series    
DOI: 10.1016/S0070-2153(06)76001-X     Document Type: Review

References (232)

1. Aikawa T., Segre G.V., and Lee K. Fibroblast growth factor inhibits chondrocytic growth through induction of p21 and subsequent inactivation of cyclin E-Cdk2. J. Biol. Chem. 276 (2001) 29347-29352
2. Akiyama H., Lyons J.P., Mori-Akiyama Y., Yang X., Zhang R., Zhang Z., Deng J.M., Taketo M.M., Nakamura T., Behringer R.R., McCrea P.D., and de Crombrugghe B. Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev. 18 (2004) 1072-1087
3. Akiyama H., Kamitani T., Yang X., Kandyil R., Bridgewater L.C., Fellous M., Mori-Akiyama Y., and de Crombrugghe B. The transcription factor Sox9 is degraded by the ubiquitin-proteasome system and stabilized by a mutation in a ubiquitin-target site. Matrix Biol. 23 (2005) 499-505
4. 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 (2004) 685-699
5. Alvarez J., Horton J., Sohn P., and Serra R. The perichondrium plays an important role in mediating the effects of TGF-beta1 on endochondral bone formation. Dev. Dyn. 221 (2001) 311-321
6. Alvarez J., Sohn P., Zeng X., Doetschman T., Robbins D.J., and Serra R. TGF-beta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Development 129 (2002) 1913-1924
7. Arteaga-Solis E., Gayraud B., Lee S.Y., Shum L., Sakai L., and Ramirez F. Regulation of limb patterning by extracellular microfibrils. J. Cell. Biol. 154 (2001) 275-281
8. Aubin J., Davy A., and Soriano P. In vivo convergence of BMP and MAPK signaling pathways: Impact of differential Smad1 phosphorylation on development and homeostasis. Genes Dev. 18 (2004) 1482-1494
9. Babitt J.L., Zhang Y., Samad T.A., Xia Y., Tang J., Campagna J.A., Schneyer A.L., Woolf C.J., and Lin H.Y. Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor. J. Biol. Chem. 280 (2005) 29820-29827
10. Bachiller D., Klingensmith J., Shneyder N., Tran U., Anderson R., Rossant J., and De Robertis E.M. The role of chordin/Bmp signals in mammalian pharyngeal development and DiGeorge syndrome. Development 130 (2003) 3567-3578
11. 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 (2004) 124-142
12. Balemans W., and Van Hul W. Extracellular regulation of BMP signaling in vertebrates: A cocktail of modulators. Dev. Biol. 250 (2002) 231-250
13. Ballock R.T., and O'Keefe R.J. Physiology and pathophysiology of the growth plate. Birth Defects Res. C Embryo. Today 69 (2003) 123-143
14. Ballock R.T., Heydemann A., Wakefield L.M., Flanders K.C., Roberts A.B., and Sporn M.B. TGF-beta 1 prevents hypertrophy of epiphyseal chondrocytes: Regulation of gene expression for cartilage matrix proteins and metalloproteases. Dev. Biol. 158 (1993) 414-429
15. Baur S.T., Mai J.J., and Dymecki S.M. Combinatorial signaling through BMP receptor IB and GDF5: Shaping of the distal mouse limb and the genetics of distal limb diversity. Development 127 (2000) 605-619
16. Bi W., Deng J.M., Zhang Z., Behringer R.R., and de Crombrugghe B. Sox9 is required for cartilage formation. Nat. Genet. 22 (1999) 85-89
17. Bianco P., Cancedda F.D., Riminucci M., and Cancedda R. Bone formation via cartilage models: The "borderline" chondrocyte. Matrix Biol. 17 (1998) 185-192
18. Bicknell L.S., Morgan T., Bonafe L., Wessels M.W., Bialer M.G., Willems P.J., Cohn D.H., Krakow D., and Robertson S.P. Mutations in FLNB cause boomerang dysplasia. J. Med. Genet. 42 (2005) e43
19. Brunet L.J., McMahon J.A., McMahon A.P., and Harland R.M. Noggin, cartilage morphogenesis, and joint formation in the mammalian skeleton. Science 280 (1998) 1455-1457
20. Canalis E., Economides A.N., and Gazzerro E. Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr. Rev. 24 (2003) 218-235
21. Capdevila J., and Johnson R.L. Endogenous and ectopic expression of noggin suggests a conserved mechanism for regulation of BMP function during limb and somite patterning. Dev. Biol. 197 (1998) 205-217
22. Chang H., Huylebroeck D., Verschueren K., Guo Q., Matzuk M.M., and Zwijsen A. Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Development 126 (1999) 1631-1642
23. Chang S.C., Hoang B., Thomas J.T., Vukicevic S., Luyten F.P., Ryba N.J., Kozak C.A., Reddi A.H., and Moos Jr. M. Cartilage-derived morphogenetic proteins. New members of the transforming growth factor-beta superfamily predominantly expressed in long bones during human embryonic development. J. Biol. Chem. 269 (1994) 28227-28234
24. Cheng H., Jiang W., Phillips F.M., Haydon R.C., Peng Y., Zhou L., Luu H.H., An N., Breyer B., Vanichakarn P., Szatkowski J.P., Park J.Y., et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J. Bone Joint Surg. Am. 85A (2003) 1544-1552
25. Chimal-Monroy J., Rodriguez-Leon J., Montero J.A., Ganan Y., Macias D., Merino R., and Hurle J.M. Analysis of the molecular cascade responsible for mesodermal limb chondrogenesis: Sox genes and BMP signaling. Dev. Biol. 257 (2003) 292-301
26. Chu G.C., Dunn N.R., Anderson D.C., Oxburgh L., and Robertson E.J. Differential requirements for Smad4 in TGF-beta-dependent patterning of the early mouse embryo. Development 131 (2004) 3501-3512
27. Colvin J.S., Bohne B.A., Harding G.W., McEwen D.G., and Ornitz D.M. Skeletal overgrowth and deafness in mice lacking fibroblast growth factor receptor 3. Nat. Genet. 12 (1996) 390-397
28. Dailey L., Laplantine E., Priore R., and Basilico C. A network of transcriptional and signaling events is activated by FGF to induce chondrocyte growth arrest and differentiation. J. Cell. Biol. 161 (2003) 1053-1066
29. Datto M., and Wang X.F. Ubiquitin-mediated degradation a mechanism for fine-tuning TGF-beta signaling. Cell 121 (2005) 2-4
30. De Luca F., Barnes K.M., Uyeda J.A., De-Levi S., Abad V., Palese T., Mericq V., and Baron J. Regulation of growth plate chondrogenesis by bone morphogenetic protein-2. Endocrinology 142 (2001) 430-436
31. De Robertis E.M., and Kuroda H. Dorsal-ventral patterning and neural induction in Xenopus embryos. Annu. Rev. Cell Dev. Biol. 20 (2004) 285-308
32. Delaune E., Lemaire P., and Kodjabachian L. Neural induction in Xenopus requires early FGF signalling in addition to BMP inhibition. Development 132 (2005) 299-310
33. Demirhan O., Turkmen S., Schwabe G.C., Soyupak S., Akgul E., Tastemir D., Karahan D., Mundlos S., and Lehmann K. A homozygous BMPR1B mutation causes a new subtype of acromesomelic chondrodysplasia with genital anomalies. J. Med. Genet. 42 (2005) 314-317
34. Deng C., Wynshaw-Boris A., Zhou F., Kuo A., and Leder P. Fibroblast growth factor receptor 3 is a negative regulator of bone growth. Cell 84 (1996) 911-921
35. Denker A.E., Haas A.R., Nicoll S.B., and Tuan R.S. Chondrogenic differentiation of murine C3H10T1/2 multipotential mesenchymal cells: I. Stimulation by bone morphogenetic protein-2 in high-density micromass cultures. Differentiation 64 (1999) 67-76
36. Derynck R., and Zhang Y.E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 425 (2003) 577-584
37. Desgrosellier J.S., Mundell N.A., McDonnell M.A., Moses H.L., and Barnett J.V. Activin receptor-like kinase 2 and Smad6 regulate epithelial-mesenchymal transformation during cardiac valve formation. Dev. Biol. 280 (2005) 201-210
38. Dickson M.C., Martin J.S., Cousins F.M., Kulkarni A.B., Karlsson S., and Akhurst R.J. Defective haematopoiesis and vasculogenesis in transforming growth factor-beta 1 knock out mice. Development 121 (1995) 1845-1854
39. Dietz H.C., and Pyeritz R.E. Mutations in the human gene for fibrillin-1 (FBN) in the Marfan syndrome and related disorders. Hum. Molec. Genet. 4 (1995) 1799-1809
40. DiLeone R.J., Marcus G.A., Johnson M.D., and Kingsley D.M. Efficient studies of long-distance Bmp5 gene regulation using bacterial artificial chromosomes. Proc. Natl. Acad. Sci. USA 97 (2000) 1612-1617
41. Drissi H., Zuscik M., Rosier R., and O'Keefe R. Transcriptional regulation of chondrocyte maturation: Potential involvement of transcription factors in OA pathogenesis. Mol. Aspects Med. 26 (2005) 169-179
42. Drissi M.H., Li X., Sheu T.J., Zuscik M.J., Schwarz E.M., Puzas J.E., Rosier R.N., and O'Keefe R.J. 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 (2003) 1287-1298
43. Dudley A.T., and Robertson E.J. Overlapping expression domains of bone morphogenetic protein family members potentially account for limited tissue defects in BMP7 deficient embryos. Dev. Dyn. 208 (1997) 349-362
44. Dupont S., Zacchigna L., Cordenonsi M., Soligo S., Adorno M., Rugge M., and Piccolo S. Germ-layer specification and control of cell growth by ectodermin, a Smad4 ubiquitin ligase. Cell 121 (2005) 87-99
45. Ebara S., and Nakayama K. Mechanism for the action of bone morphogenetic proteins and regulation of their activity. Spine 27 (2002) S10-S15
46. Ellingsworth L.R., Brennan J.E., Fok K., Rosen D.M., Bentz H., Piez K.A., and Seyedin S.M. Antibodies to the N-terminal portion of cartilage-inducing factor A and transforming growth factor beta. Immunohistochemical localization and association with differentiating cells. J. Biol. Chem. 261 (1986) 12362-12367
47. Enomoto-Iwamoto M., Iwamoto M., Mukudai Y., Kawakami Y., Nohno T., Higuchi Y., Takemoto S., Ohuchi H., Noji S., and Kurisu K. Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes. J. Cell. Biol. 140 (1998) 409-418
48. Enomoto-Iwamoto M., Kitagaki J., Koyama E., Tamamura Y., Wu C., Kanatani N., Koike T., Okada H., Komori T., Yoneda T., Church V., Francis-West P.H., et al. The Wnt antagonist Frzb-1 regulates chondrocyte maturation and long bone development during limb skeletogenesis. Dev. Biol. 251 (2002) 142-156
49. Erlacher L., McCartney J., Piek E., ten Dijke P., Yanagishita M., Oppermann H., and Luyten F. Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis. J. Bone Miner. Res. 13 (1998) 383-392
50. Faiyaz-Ul-Haque M., Ahmad W., Zaidi S.H., Haque S., Teebi A.S., Ahmad M., Cohn D.H., and Tsui L.C. Mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene in a kindred affected with fibular hypoplasia and complex brachydactyly (DuPan syndrome). Clin. Genet. 61 (2002) 454-458
51. Fang J., and Hall B.K. Chondrogenic cell differentiation from membrane bone periostea. Anat. Embryol. (Berl.) 196 (1997) 349-362
52. Feng X.H., and Derynck R. Specificity and versatility in tgf-beta signaling through Smads. Annu. Rev. Cell Dev. Biol. 21 (2005) 659-693
53. Ferguson C.M., Schwarz E.M., Reynolds P.R., Puzas J.E., Rosier R.N., and O'Keefe R.J. Smad2 and 3 mediate transforming growth factor-beta1-induced inhibition of chondrocyte maturation. Endocrinology 141 (2000) 4728-4735
54. Fernandez-Lloris R., Vinals F., Lopez-Rovira T., Harley V., Bartrons R., Rosa J.L., and Ventura F. Induction of the Sry-related factor SOX6 contributes to bone morphogenetic protein-2-induced chondroblastic differentiation of C3H10T1/2 cells. Mol. Endocrinol. 17 (2003) 1332-1343
55. Fisher M.C., Li Y., Seghatoleslami M.R., Dealy C.N., and Kosher R.A. Heparan sulfate proteoglycans including syndecan-3 modulate BMP activity during limb cartilage differentiation. Matrix Biol. 25 (2006) 27-39
56. Fujii M., Takeda K., Imamura T., Aoki H., Sampath T.K., Enomoto S., Kawabata M., Kato M., Ichijo H., and Miyazono K. Roles of bone morphogenetic protein type I receptors and Smad proteins in osteoblast and chondroblast differentiation. Mol. Biol. Cell 10 (1999) 3801-3813
57. 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 (2005) 8343-8350
58. Furumatsu T., Tsuda M., Yoshida K., Taniguchi N., Ito T., Hashimoto M., and Asahara H. Sox9 and p300 cooperatively regulate chromatin-mediated transcription. J. Biol. Chem. 280 (2005) 35203-35208
59. Gatherer D., Ten Dijke P., Baird D.T., and Akhurst R.J. Expression of TGF-beta isoforms during first trimester human embryogenesis. Development 110 (1990) 445-460
60. Goldring M.B., Tsuchimochi K., and Ijiri K. The control of chondrogenesis. J. Cell. Biochem. 97 (2006) 33-44
61. Gong Y., Krakow D., Marcelino J., Wilkin D., Chitayat D., Babul-Hirji R., Hudgins L., Cremers C.W., Cremers F.P., Brunner H.G., Reinker K., Rimoin D.L., et al. Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. Nat. Genet. 21 (1999) 302-304
62. Goumans M.J., Valdimarsdottir G., Itoh S., Lebrin F., Larsson J., Mummery C., Karlsson S., and ten Dijke P. Activin receptor-like kinase (ALK)1 is an antagonistic mediator of lateral TGF-beta/ALK5 signaling. Mol. Cell 12 (2003) 817-828
63. Gregory K.E., Ono R.N., Charbonneau N.L., Kuo C.L., Keene D.R., Bachinger H.P., and Sakai L.Y. The prodomain of BMP7 targets the BMP7 complex to the extracellular matrix. J. Biol. Chem. 280 (2005) 27970-27980
64. Grimsrud C.D., Romano P.R., D'Souza M., Puzas J.E., Reynolds P.R., Rosier R.N., and O'Keefe R.J. BMP6 is an autocrine stimulator of chondrocyte differentiation. J. Bone Miner. Res. 14 (1999) 475-482
65. Guo X., Day T.F., Jiang X., Garrett-Beal L., Topol L., and Yang Y. Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation. Genes Dev. 18 (2004) 2404-2417
66. Haas A.R., and Tuan R.S. Chondrogenic differentiation of murine C3H10T1/2 multipotential mesenchymal cells: II. Stimulation by bone morphogenetic protein-2 requires modulation of N-cadherin expression and function. Differentiation 64 (1999) 77-89
67. Hartmann C., and Tabin C.J. Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development 127 (2000) 3141-3159
68. 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 (1998) 186-197
69. Hatakeyama Y., Nguyen J., Wang X., Nuckolls G.H., and Shum L. Smad signaling in mesenchymal and chondroprogenitor cells. J. Bone Joint Surg. Am. 85A Suppl. 3 (2003) 13-18
70. Hayashi K., Kobayashi T., Umino T., Goitsuka R., Matsui Y., and Kitamura D. SMAD1 signaling is critical for initial commitment of germ cell lineage from mouse epiblast. Mech. Dev. 118 (2002) 99-109
71. Hill T.P., Spater D., Taketo M.M., Birchmeier W., and Hartmann C. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev. Cell 8 (2005) 727-738
72. Hilton M.J., Tu X., Cook J., Hu H., and Long F. Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development. Development 132 (2005) 4339-4351
73. Holland T.A., and Mikos A.G. Advances in drug delivery for articular cartilage. J. Control Release 86 (2003) 1-14
74. Ijiri K., Zerbini L.F., Peng H., Correa R.G., Lu B., Walsh N., Zhao Y., Taniguchi N., Huang X.L., Otu H., Wang H., Wang J.F., et al. A novel role for GADD45beta as a mediator of MMP-13 gene expression during chondrocyte terminal differentiation. J. Biol. Chem. 280 (2005) 38544-38555
75. Irie A., Habuchi H., Kimata K., and Sanai Y. Heparan sulfate is required for bone morphogenetic protein-7 signaling. Biochem. Biophys. Res. Commun. 308 (2003) 858-865
76. Ishida W., Hamamoto T., Kusanagi K., Yagi K., Kawabata M., Takehara K., Sampath T.K., Kato M., and Miyazono K. Smad6 is a Smad1/5-induced Smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter. J. Biol. Chem. 275 (2000) 6075-6079
77. Ito H., Akiyama H., Shigeno C., and Nakamura T. Noggin and bone morphogenetic protein-4 coordinately regulate the progression of chondrogenic differentiation in mouse clonal EC cells, ATDC5. Biochem. Biophys. Res. Commun. 260 (1999) 240-244
78. Ito Y., Bringas Jr. P., Mogharei A., Zhao J., Deng C., and Chai Y. Receptor-regulated and inhibitory Smads are critical in regulating transforming growth factor beta-mediated Meckel's cartilage development. Dev. Dyn. 224 (2002) 69-78
79. Ivkovic S., Yoon B.S., Popoff S.N., Safadi F.F., Libuda D.E., Stephenson R.C., Daluiski A., and Lyons K.M. Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development 130 (2003) 2779-2791
80. Jones C.M., Lyons K.M., and Hogan B.L. Involvement of bone morphogenetic protein-4 (BMP-4) and Vgr-1 in morphogenesis and neurogenesis in the mouse. Development 111 (1991) 531-542
81. Ju W., Hoffmann A., Verschueren K., Tylzanowski P., Kaps C., Gross G., and Huylebroeck D. The bone morphogenetic protein 2 signaling mediator Smad1 participates predominantly in osteogenic and not in chondrogenic differentiation in mesenchymal progenitors C3H10T1/2. J. Bone Miner. Res. 15 (2000) 1889-1899
82. Kaartinen V., Voncken J.W., Shuler C., Warburton D., Bu D., Heisterkamp N., and Groffen J. Abnormal lung development and cleft palate in mice lacking TGF-beta 3 indicates defects of epithelial-mesenchymal interaction. Nat. Genet. 11 (1995) 415-421
83. Kameda T., Koike C., Saitoh K., Kuroiwa A., and Iba H. Developmental patterning in chondrocytic cultures by morphogenic gradients: BMP induces expression of Indian hedgehog and noggin. Genes Cells 4 (1999) 175-184
84. Kato H.D., Terao Y., Ogawa M., Matsuda T., Arima T., Kato K., Yong Z., and Wake N. Growth-associated gene expression profiles by microarray analysis of trophoblast of molar pregnancies and normal villi. Int. J. Gynecol. Pathol. 21 (2002) 255-260
85. Kawai S., and Sugiura T. Characterization of human bone morphogenetic protein (BMP)-4 and -7 gene promoters: Activation of BMP promoters by Gli, a sonic hedgehog mediator. Bone 29 (2001) 54-61
86. Kawakami Y., Ishikawa T., Shimabara M., Tanda N., Enomoto-Iwamoto M., Iwamoto M., Kuwana T., Ueki A., Noji S., and Nohno T. BMP signaling during bone pattern determination in the developing limb. Development 122 (1996) 3557-3566
87. Kim I.S., Otto F., Zabel B., and Mundlos S. Regulation of chondrocyte differentiation by Cbfa1. Mech. Dev. 80 (1999) 159-170
88. Kingsley D.M. What do BMPs do in mammals? Clues from the mouse short-ear mutation. Trends Genet. 10 (1994) 16-21
89. Kluppel M., Wight T.N., Chan C., Hinek A., and Wrana J.L. Maintenance of chondroitin sulfation balance by chondroitin-4-sulfotransferase 1 is required for chondrocyte development and growth factor signaling during cartilage morphogenesis. Development 132 (2005) 3989-4003
90. Kobayashi T., and Kronenberg H. Minireview: Transcriptional regulation in development of bone. Endocrinology 146 (2005) 1012-1017
91. Kobayashi T., Lyons K.M., McMahon A.P., and Kronenberg H.M. BMP signaling stimulates cellular differentiation at multiple steps during cartilage development. Proc. Natl. Acad. Sci. USA 102 (2005) 18023-18027
92. Koziel L., Wuelling M., Schneider S., and Vortkamp A. Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation. Development 132 (2005) 5249-5260
93. Krakow D., Robertson S.P., King L.M., Morgan T., Sebald E.T., Bertolotto C., Wachsmann-Hogiu S., Acuna D., Shapiro S.S., Takafuta T., Aftimos S., Kim C.A., et al. Mutations in the gene encoding filamin B disrupt vertebral segmentation, joint formation and skeletogenesis. Nat. Genet. 36 (2004) 405-410
94. Kramer J., Hegert C., Guan K., Wobus A.M., Muller P.K., and Rohwedel J. Embryonic stem cell-derived chondrogenic differentiation in-vitro: Activation by BMP2 and BMP-4. Mech. Dev. 92 (2000) 193-205
95. Krejci P., Masri B., Fontaine V., Mekikian P.B., Weis M., Prats H., and Wilcox W.R. Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis. J. Cell Sci. 118 (2005) 5089-5100
96. Kretzschmar M., Doody J., and Massagué J. Opposing BMP and EGF signalling pathway converge on the TGF-ß family mediator Smad1. Nature 389 (1997) 618-622
97. Kronenberg H.M. Developmental regulation of the growth plate. Nature 423 (2003) 332-336
98. Kugimiya F., Kawaguchi H., Kamekura S., Chikuda H., Ohba S., Yano F., Ogata N., Katagiri T., Harada Y., Azuma Y., Nakamura K., and Chung U.I. Involvement of endogenous bone morphogenetic protein (BMP) 2 and BMP6 in bone formation. J. Biol. Chem. 280 (2005) 35704-35712
99. Kulyk W.M., Rodgers B.J., Greer K., and Kosher R.A. Promotion of embryonic chick limb cartilage differentiation by transforming growth factor-beta. Dev. Biol. 135 (1989) 424-430
100. Kuroda H., Fuentealba L., Ikeda A., Reversade B., and De Robertis E.M. Default neural induction: Neuralization of dissociated Xenopus cells is mediated by Ras/MAPK activation. Genes Dev. 19 (2005) 1022-1027
101. Lai C.F., Feng X., Nishimura R., Teitelbaum S.L., Avioli L.V., Ross F.P., and Cheng S.L. Transforming growth factor-beta up-regulates the beta 5 integrin subunit expression via Sp1 and Smad signaling. J. Biol. Chem. 275 (2000) 36400-36406
102. Laplantine E., Rossi F., Sahni M., Basilico C., and Cobrinik D. FGF signaling targets the pRb-related p107 and p130 proteins to induce chondrocyte growth arrest. J. Cell Biol. 158 (2002) 741-750
103. Larsson J., Goumans M.J., Sjostrand L.J., van Rooijen M.A., Ward D., Leveen P., Xu X., ten Dijke P., Mummery C.L., and Karlsson S. Abnormal angiogenesis but intact hematopoietic potential in TGF-beta type I receptor-deficient mice. EMBO J. 20 (2001) 1663-1673
104. Lechleider R.J., Ryan J.L., Garrett L., Eng C., Deng C., Wynshaw-Boris A., and Roberts A.B. Targeted mutagenesis of Smad1 reveals an essential role in chorioallantoic fusion. Dev. Biol. 240 (2001) 157-167
105. Lehmann K., Seemann P., Stricker S., Sammar M., Meyer B., Suring K., Majewski F., Tinschert S., Grzeschik K.H., Muller D., Knaus P., Nurnberg P., et al. Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2. Proc. Natl. Acad. Sci. USA 100 (2003) 12277-12282
106. Levy L., and Hill C.S. Smad4 dependency defines two classes of transforming growth factor {beta} (TGF-{beta}) target genes and distinguishes TGF-{beta}-induced epithelial-mesenchymal transition from its antiproliferative and migratory responses. Mol. Cell. Biol. 25 (2005) 8108-8125
107. Li T.F., O'Keefe R.J., and Chen D. TGF-beta signaling in chondrocytes. Front. Biosci. 10 (2005) 681-688
108. Li T.F., Darowish M., Zuscik M.J., Chen D., Schwarz E.M., Rosier R.N., Drissi H., and O'Keefe R.J. Smad3-deficient chondrocytes have enhanced BMP signaling and accelerated differentiation. J. Bone Miner. Res. 21 (2006) 4-16
109. Lin J., Patel S.R., Cheng X., Cho E.A., Levitan I., Ullenbruch M., Phan S.H., Park J.M., and Dressler G.R. Kielin/chordin-like protein, a novel enhancer of BMP signaling, attenuates renal fibrotic disease. Nat. Med. 11 (2005) 387-393
110. Liu F., Massague J., and Ruiz i Altaba A. Carboxy-terminally truncated Gli3 proteins associate with Smads. Nat. Genet. 20 (1998) 325-326
111. Logan C.Y., and Nusse R. The Wnt signaling pathway in development and disease. Annu. Rev. Cell. Dev. Biol. 20 (2004) 781-810
112. Long F., Chung U.I., Ohba S., McMahon J., Kronenberg H.M., and McMahon A.P. Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton. Development 131 (2004) 1309-1318
113. Luyten F.P. Mesenchymal stem cells in osteoarthritis. Curr. Opin. Rheumatol. 16 (2004) 599-603
114. Lyons K.M., Pelton R.W., and Hogan B.L. Organogenesis and pattern formation in the mouse: RNA distribution patterns suggest a role for bone morphogenetic protein-2A (BMP2A). Development 109 (1990) 833-844
115. Lyons K.M., Hogan B.L., and Robertson E.J. Colocalization of BMP7 and BMP2 RNAs suggests that these factors cooperatively mediate tissue interactions during murine development. Mech. Dev. 50 (1995) 71-83
116. Macias D., Ganan Y., Sampath T.K., Piedra M.E., Ros M.A., and Hurle J.M. Role of BMP2 and OP-1 (BMP7) in programmed cell death and skeletogenesis during chick limb development. Development 124 (1997) 1109-1117
117. Macias-Silva M., Hoodless P.A., Tang S.J., Buchwald M., and Wrana J.L. Specific activation of Smad1 signaling pathways by the BMP7 type I receptor, ALK2. J. Biol. Chem. 273 (1998) 25628-25636
118. Majumdar M.K., Wang E., and Morris E.A. BMP2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1. J. Cell. Physiol. 189 (2001) 275-284
119. Massague J. TGF-beta signal transduction. Annu. Rev. Biochem. 67 (1998) 753-791
120. Massague J., Seoane J., and Wotton D. Smad transcription factors. Genes Dev. 19 (2005) 2783-2810
121. McMahon J.A., Takada S., Zimmerman L.B., Fan C.M., Harland R.M., and McMahon A.P. Noggin-mediated antagonism of BMP signaling is required for growth and patterning of the neural tube and somite. Genes Dev. 12 (1998) 1438-1452
122. Meech R., Edelman D.B., Jones F.S., and Makarenkova H.P. The homeobox transcription factor Barx2 regulates chondrogenesis during limb development. Development 132 (2005) 2135-2146
123. Meraz M.A., White J.M., Sheehan K.C., Bach E.A., Rodig S.J., Dighe A.S., Kaplan D.H., Riley J.K., Greenlund A.C., Campbell D., Carver-Moore K., DuBois R.N., et al. Targeted disruption of the Stat1 gene in mice reveals unexpected physiologic specificity in the JAK-STAT signaling pathway. Cell 84 (1996) 431-442
124. Millan F.A., Denhez F., Kondaiah P., and Akhurst R.J. Embryonic gene expression patterns of TGF-beta 1, beta 2 and beta 3 suggest different developmental functions in-vivo. Development 111 (1991) 131-143
125. Minina E., Wenzel H.M., Kreschel C., Karp S., Gaffield W., McMahon A.P., and Vortkamp A. BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation. Development 128 (2001) 4523-4534
126. Minina E., Kreschel C., Naski M.C., Ornitz D.M., and Vortkamp A. Interaction of FGF, Ihh/Pthlh, and BMP signaling integrates chondrocyte proliferation and hypertrophic differentiation. Dev. Cell 3 (2002) 439-449
127. Minina E., Schneider S., Rosowski M., Lauster R., and Vortkamp A. Expression of Fgf and TGF-beta signaling related genes during embryonic endochondral ossification. Gene Expr. Patterns 6 (2005) 102-109
128. Miyazono K., Kusanagi K., and Inoue H. Divergence and convergence of TGF-beta/BMP signaling. J. Cell. Physiol. 187 (2001) 265-276
129. Morales T.I., Joyce M.E., Sobel M.E., Danielpour D., and Roberts A.B. Transforming growth factor-beta in calf articular cartilage organ cultures: Synthesis and distribution. Arch. Biochem. Biophys. 288 (1991) 397-405
130. Mortlock D.P., Guenther C., and Kingsley D.M. A general approach for identifying distant regulatory elements applied to the Gdf6 gene. Genome Res. 13 (2003) 2069-2081
131. Moses H.L., and Serra R. Regulation of differentiation by TGF-beta. Curr. Opin. Genet. Dev. 6 (1996) 581-586
132. Moustakas A., and Heldin C.H. Non-Smad TGF-beta signals. J. Cell Sci. 118 (2005) 3573-3584
133. 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 (2003) 2809-2817
134. Murakami S., Balmes G., McKinney S., Zhang Z., Givol D., and de Crombrugghe B. Constitutive activation of MEK1 in chondrocytes causes Stat1-independent achondroplasia-like dwarfism and rescues the Fgfr3-deficient mouse phenotype. Genes. Dev. 18 (2004) 290-305
135. Nakamura K., Shirai T., Morishita S., Uchida S., Saeki-Miura K., and Makishima F. p38 mitogen-activated protein kinase functionally contributes to chondrogenesis induced by growth/differentiation factor-5 in ATDC5 cells. Exp. Cell. Res. 250 (1999) 351-363
136. Nakashima K., and de Crombrugghe B. Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet. 19 (2003) 458-466
137. Nakashima K., Zhou X., Kunkel G., Zhang Z., Deng J.M., Behringer R.R., and de Crombrugghe B. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell 108 (2002) 17-29
138. Naski M.C., Colvin J.S., Coffin J.D., and Ornitz D.M. Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3. Development 125 (1998) 4977-4988
139. Nelson W.J., and Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways. Science 303 (2004) 1483-1487
140. Neptune E.R., Frischmeyer P.A., Arking D.E., Myers L., Bunton T.E., Gayraud B., Ramirez F., Sakai L.Y., and Dietz H.C. Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome. Nat. Genet. 33 (2003) 407-411
141. Nifuji A., and Noda M. Coordinated expression of noggin and bone morphogenetic proteins (BMPs) during early skeletogenesis and induction of noggin expression by BMP7. J. Bone Miner. Res. 14 (1999) 2057-2066
142. Nifuji A., Kellermann O., and Noda M. Noggin inhibits chondrogenic but not osteogenic differentiation in mesodermal stem cell line C1 and skeletal cells. Endocrinology 145 (2004) 3434-3442
143. Nishitoh H., Ichijo H., Kimura M., Matsumoto T., Makishima F., Yamaguchi A., Yamashita H., Enomoto S., and Miyazono K. Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5. J. Biol. Chem. 271 (1996) 21345-21352
144. Nomura M., and Li E. Smad2 role in mesoderm formation, left-right patterning and craniofacial development. Nature 393 (1998) 786-790
145. Ohbayashi N., Shibayama M., Kurotaki Y., Imanishi M., Fujimori T., Itoh N., and Takada S. FGF18 is required for normal cell proliferation and differentiation during osteogenesis and chondrogenesis. Genes Dev. 16 (2002) 870-879
146. Okada A., Shiomi T., Aoki Y., and Fujiwara M. Phenytoin stimulates chondrogenic differentiation in mouse clonal chondrogenic EC cells, ATDC5. J. Toxicol. Sci. 30 (2005) 145-156
147. Olney R.C., Wang J., Sylvester J.E., and Mougey E.B. Growth factor regulation of human growth plate chondrocyte proliferation in-vitro. Biochem. Biophys. Res. Commun. 317 (2004) 1171-1182
148. Ornitz D.M., and Marie P.J. FGF signaling pathways in endochondral and intramembranous bone development and human genetic disease. Genes Dev. 16 (2002) 1446-1465
149. Oshima M., Oshima H., and Taketo M.M. TGF-beta receptor type II deficiency results in defects of yolk sac hematopoiesis and vasculogenesis. Dev. Biol. 179 (1996) 297-302
150. Parr B.A., Shea M.J., Vassileva G., and McMahon A.P. Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds. Development 119 (1993) 247-261
151. Pathi S., Rutenberg J.B., Johnson R.L., and Vortkamp A. Interaction of Ihh and BMP/noggin signaling during cartilage differentiation. Dev. Biol. 209 (1999) 239-253
152. Pelton R.W., Hogan B.L., Miller D.A., and Moses H.L. Differential expression of genes encoding TGFs beta 1, beta 2, and beta 3 during murine palate formation. Dev. Biol. 141 (1990) 456-460
153. 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 (2003) 3023-3028
154. Peters K., Ornitz D., Werner S., and Williams L. Unique expression pattern of the FGF receptor 3 gene during mouse organogenesis. Dev Biol. 155 (1993) 423-430
155. Peterson R.S., Andhare R.A., Rousche K.T., Knudson W., Wang W., Grossfield J.B., Thomas R.O., Hollingsworth R.E., and Knudson C.B. CD44 modulates Smad1 activation in the BMP7 signaling pathway. J. Cell. Biol. 166 (2004) 1081-1091
156. Pittenger M.F., Mackay A.M., Beck S.C., Jaiswal R.K., Douglas R., Mosca J.D., Moorman M.A., Simonetti D.W., Craig S., and Marshak D.R. Multilineage potential of adult human mesenchymal stem cells. Science 284 (1999) 143-147
157. Pizette S., and Niswander L. BMPs are required at two steps of limb chondrogenesis: Formation of prechondrogenic condensations and their differentiation into chondrocytes. Dev. Biol. 219 (2000) 237-249
158. Polinkovsky A., Robin N.H., Thomas J.T., Irons M., Lynn A., Goodman F.R., Reardon W., Kant S.G., Brunner H.G., van der Burgt I., Chitayat D., McGaughran J., et al. Mutations in CDMP1 cause autosomal dominant brachydactyly type C. Nat. Genet. 17 (1997) 18-19
159. Proetzel G., Pawlowski S.A., Wiles M.V., Yin M., Boivin G.P., Howles P.N., Ding J., Ferguson M.W., and Doetschman T. Transforming growth factor-beta 3 is required for secondary palate fusion. Nat. Genet. 11 (1995) 409-414
160. Provot S., and Schipani E. Molecular mechanisms of endochondral bone development. Biochem. Biophys. Res. Commun. 328 (2005) 658-665
161. Qiao B., Padilla S.R., and Benya P.D. Transforming growth factor (TGF)-beta-activated kinase 1 mimics and mediates TGF-beta-induced stimulation of type II collagen synthesis in chondrocytes independent of Col2a1 transcription and Smad3 signaling. J. Biol. Chem. 280 (2005) 17562-17571
162. Raucci A., Laplantine E., Mansukhani A., and Basilico C. Activation of the ERK1/2 and p38 mitogen-activated protein kinase pathways mediates fibroblast growth factor-induced growth arrest of chondrocytes. J. Biol. Chem. 279 (2004) 1747-1756
163. Reilly G.C., Golden E.B., Grasso-Knight G., and Leboy P.S. Differential effects of ERK and p38 signaling in BMP2 stimulated hypertrophy of cultured chick sternal chondrocytes. Cell Commun. Signal. 3 (2005) 3
164. Roach H.I., Erenpreisa J., and Aigner T. Osteogenic differentiation of hypertrophic chondrocytes involves asymmetric cell divisions and apoptosis. J. Cell Biol. 131 (1995) 483-494
165. Ryu J.H., Kim S.J., Kim S.H., Oh C.D., Hwang S.G., Chun C.H., Oh S.H., Seong J.K., Huh T.L., and Chun J.S. Regulation of the chondrocyte phenotype by beta-catenin. Development 129 (2002) 5541-5550
166. Sahni M., Ambrosetti D.C., Mansukhani A., Gertner R., Levy D., and Basilico C. FGF signaling inhibits chondrocyte proliferation and regulates bone development through the STAT-1 pathway. Genes Dev. 13 (1999) 1361-1366
167. Sahni M., Raz R., Coffin J.D., Levy D., and Basilico C. STAT1 mediates the increased apoptosis and reduced chondrocyte proliferation in mice overexpressing FGF2. Development 128 (2001) 2119-2129
168. Sakai L.Y., Keene D.R., and Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J. Cell Biol. 103 (1986) 2499-2509
169. 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 (1999) 1145-1152
170. Samad T.A., Rebbapragada A., Bell E., Zhang Y., Sidis Y., Jeong S.J., Campagna J.A., Perusini S., Fabrizio D.A., Schneyer A.L., Lin H.Y., Brivanlou A.H., et al. DRAGON, a bone morphogenetic protein co-receptor. J. Biol. Chem. 280 (2005) 14122-14129
171. Sammar M., Stricker S., Schwabe G.C., Sieber C., Hartung A., Hanke M., Oishi I., Pohl J., Minami Y., Sebald W., Mundlos S., and Knaus P. Modulation of GDF5/BRI-b signalling through interaction with the tyrosine kinase receptor Ror2. Genes Cells 9 (2004) 1227-1238
172. Sandberg M., Vuorio T., Hirvonen H., Alitalo K., and Vuorio E. Enhanced expression of TGF-beta and c-fos mRNAs in the growth plates of developing human long bones. Development 102 (1988) 461-470
173. Sanford L.P., Ormsby I., Gittenberger-de Groot A.C., Sariola H., Friedman R., Boivin G.P., Cardell E.L., and Doetschman T. TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. Development 124 (1997) 2659-2670
174. Sasaki A., Masuda Y., Ohta Y., Ikeda K., and Watanabe K. Filamin associates with Smads and regulates transforming growth factor-beta signaling. J. Biol. Chem. 276 (2001) 17871-17877
175. Satoh A., Suzuki M., Amano T., Tamura K., and Ide H. Joint development in Xenopus laevis and induction of segmentations in regenerating froglet limb (spike). Dev. Dyn. 233 (2005) 1444-1453
176. Schwabe G.C., Turkmen S., Leschik G., Palanduz S., Stover B., Goecke T.O., and Mundlos S. Brachydactyly type C caused by a homozygous missense mutation in the prodomain of CDMP1. Am. J. Med. Genet. A 124 (2004) 356-363
177. Scott I.C., Blitz I.L., Pappano W.N., Maas S.A., Cho K.W., and Greenspan D.S. Homologues of twisted gastrulation are extracellular cofactors in antagonism of BMP signalling. Nature 410 (2001) 475-478
178. Seeherman H., and Wozney J.M. Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. Cytokine Growth Factor Rev. 16 (2005) 329-345
179. Seemann P., Schwappacher R., Kjaer K.W., Krakow D., Lehmann K., Dawson K., Stricker S., Pohl J., Ploger F., Staub E., Nickel J., Sebald W., et al. Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or brachydactyly type A2. J. Clin. Invest. 115 (2005) 2373-2381
180. Seghatoleslami M.R., and Kosher R.A. Inhibition of in-vitro limb cartilage differentiation by syndecan-3 antibodies. Dev. Dyn. 207 (1996) 114-119
181. Seki K., and Hata A. Indian hedgehog gene is a target of the bone morphogenetic protein signaling pathway. J. Biol. Chem. 279 (2004) 18544-18549
182. Serra R., and Chang C. TGF-beta signaling in human skeletal and patterning disorders. Birth Defects Res. C Embryo Today 69 (2003) 333-351
183. Serra R., Karaplis A., and Sohn P. Parathyroid hormone-related peptide (PTHrP)-dependent and -independent effects of transforming growth factor beta (TGF-beta) on endochondral bone formation. J. Cell Biol. 145 (1999) 783-794
184. Seto H., Kamekura S., Miura T., Yamamoto A., Chikuda H., Ogata T., Hiraoka H., Oda H., Nakamura K., Kurosawa H., Chug U.I., Kawaguchi H., et al. Distinct roles of Smad pathways and p38 pathways in cartilage-specific gene expression in synovial fibroblasts. J. Clin. Invest. 113 (2004) 718-726
185. Settle Jr. S.H., Rountree R.B., Sinha A., Thacker A., Higgins K., and Kingsley D.M. Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. Dev. Biol. 254 (2003) 116-130
186. Shi Y., and Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113 (2003) 685-700
187. Shukunami C., Ohta Y., Sakuda M., and Hiraki Y. Sequential progression of the differentiation program by bone morphogenetic protein-2 in chondrogenic cell line ATDC5. Exp. Cell Res. 241 (1998) 1-11
188. Shukunami C., Akiyama H., Nakamura T., and Hiraki Y. Requirement of autocrine signaling by bone morphogenetic protein-4 for chondrogenic differentiation of ATDC5 cells. FEBS Lett. 469 (2000) 83-87
189. Shull M.M., Ormsby I., Kier A.B., Pawlowski S., Diebold R.J., Yin M., Allen R., Sidman C., Proetzel G., Calvin D., Annunziata N., and Doetschman T. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359 (1992) 693-699
190. Sirard C., de la Pompa J.L., Elia A., Itie A., Mirtsos C., Cheung A., Hahn S., Wakeham A., Schwartz L., Kern S.E., Rossant J., and Mak T.W. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev. 12 (1998) 107-119
191. Smits P., Li P., Mandel J., Zhang Z., Deng J.M., Behringer R.R., de Crombrugghe B., and Lefebvre V. The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev. Cell 1 (2001) 277-290
192. Smits P., Dy P., Mitra S., and Lefebvre V. Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate. J. Cell Biol. 164 (2004) 747-758
193. Storm E.E., and Kingsley D.M. GDF5 coordinates bone and joint formation during digit development. Dev. Biol. 209 (1999) 11-27
194. Storm E.E., Huynh T.V., Copeland N.G., Jenkins N.A., Kingsley D.M., and Lee S.J. Limb alterations in brachypodism mice due to mutations in a new member of the TGF-beta-superfamily. Nature 368 (1994) 639-643
195. Subramanian G., Schwarz R.E., Higgins L., McEnroe G., Chakravarty S., Dugar S., and Reiss M. Targeting endogenous transforming growth factor beta receptor signaling in SMAD4-deficient human pancreatic carcinoma cells inhibits their invasive phenotype1. Cancer Res. 64 (2004) 5200-5211
196. Takada T., Katagiri T., Ifuku M., Morimura N., Kobayashi M., Hasegawa K., Ogamo A., and Kamijo R. Sulfated polysaccharides enhance the biological activities of bone morphogenetic proteins. J. Biol. Chem. 278 (2003) 43229-43235
197. Takahara M., Harada M., Guan D., Otsuji M., Naruse T., Takagi M., and Ogino T. Developmental failure of phalanges in the absence of growth/differentiation factor 5. Bone 35 (2004) 1069-1076
198. Tang Y., Katuri V., Dillner A., Mishra B., Deng C.X., and Mishra L. Disruption of transforming growth factor-beta signaling in ELF beta-spectrin-deficient mice. Science 299 (2003) 574-577
199. ten Dijke P., Yamashita H., Sampath T.K., Reddi A.H., Estevez M., Riddle D.L., Ichijo H., Heldin C.H., and Miyazono K. Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. J. Biol. Chem. 269 (1994) 16985-16988
200. Thomas J.T., Lin K., Nandedkar M., Camargo M., Cervenka J., and Luyten F.P. A human chondrodysplasia due to a mutation in a TGF-beta superfamily member. Nat. Genet. 12 (1996) 315-317
201. 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 (2001) 3609-3621
202. Tsumaki N., Tanaka K., Arikawa-Hirasawa E., Nakase T., Kimura T., Thomas J.T., Ochi T., Luyten F.P., and Yamada Y. Role of CDMP-1 in skeletal morphogenesis: Promotion of mesenchymal cell recruitment and chondrocyte differentiation. J. Cell Biol. 144 (1999) 161-173
203. Tsumaki N., Nakase T., Miyaji T., Kakiuchi M., Kimura T., Ochi T., and Yoshikawa H. Bone morphogenetic protein signals are required for cartilage formation and differently regulate joint development during skeletogenesis. J. Bone Miner. Res. 17 (2002) 898-906
204. 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 (2002) 33545-33558
205. Verbruggen G. Chondroprotective drugs in degenerative joint diseases. Rheumatology 45 (2006) 129-138
206. Volk S.W., Luvalle P., Leask T., and Leboy P.S. A BMP responsive transcriptional region in the chicken type X collagen gene. J. Bone Miner. Res. 13 (1998) 1521-1529
207. Wilkie A.O., Patey S.J., Kan S.H., van den Ouweland A.M., and Hamel B.C. FGFs, their receptors, and human limb malformations: Clinical and molecular correlations. Am. J. Med. Genet. 112 (2002) 266-278
208. Wilsman N.J., Farnum C.E., Leiferman E.M., Fry M., and Barreto C. Differential growth by growth plates as a function of multiple parameters of chondrocytic kinetics. J. Orthop. Res. 14 (1996) 927-936
209. Winnier G., Blessing M., Labosky P.A., and Hogan B.L. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev. 9 (1995) 2105-2116
210. Wisotzkey R.G., Mehra A., Sutherland D.J., Dobens L.L., Liu X., Dohrmann C., Attisano L., and Raftery L.A. Medea is a Drosophila Smad4 homolog that is differentially required to potentiate DPP responses. Development 125 (1998) 1433-1445
211. Wolfman N.M., Hattersley G., Cox K., Celeste A.J., Nelson R., Yamaji N., Dube J.L., DiBlasio-Smith E., Nove J., Song J.J., Wozney J.M., and Rosen V. Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. J. Clin. Invest. 100 (1997) 321-330
212. Wozney J.M. Bone morphogenetic proteins. Prog. Growth Factor Res. 1 (1989) 267-280
213. Wozney J.M., Rosen V., Celeste A.J., Mitsock L.M., Whitters M.J., Kriz R.W., Hewick R.M., and Wang E.A. Novel regulators of bone formation: Molecular clones and activities. Science 242 (1988) 1528-1534
214. Wu X.B., Li Y., Schneider A., Yu W., Rajendren G., Iqbal J., Yamamoto M., Alam M., Brunet L.J., Blair H.C., Zaidi M., and Abe E. Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. J. Clin. Invest. 112 (2003) 924-934
215. Yamashita H., ten Dijke P., Huylebroeck D., Sampath T.K., Andries M., Smith J.C., Heldin C.H., and Miyazono K. Osteogenic protein-1 binds to activin type II receptors and induces certain activin-like effects. J. Cell Biol. 130 (1995) 217-226
216. Yamashita M., Ying S.X., Zhang G.M., Li C., Cheng S.Y., Deng C.X., and Zhang Y.E. Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell 121 (2005) 101-113
217. 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 (2001) 35-46
218. Yeh L.C., Zavala M.C., and Lee J.C. C-type natriuretic peptide enhances osteogenic protein-1-induced osteoblastic cell differentiation via Smad5 phosphorylation. J. Cell Biochem. 97 (2006) 494-500
219. Yi S.E., Daluiski A., Pederson R., Rosen V., and Lyons K.M. The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb. Development 127 (2000) 621-630
220. Yi S.E., LaPolt P.S., Yoon B.S., Chen J.Y., Lu J.K., and Lyons K.M. The type I BMP receptor BmprIB is essential for female reproductive function. Proc. Natl. Acad. Sci. USA 98 (2001) 7994-7999
221. Yoon B.S., and Lyons K.M. Multiple functions of BMPs in chondrogenesis. J. Cell. Biochem. 93 (2004) 93-103
222. 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 (2005) 5062-5067
223. Yoshida C.A., Yamamoto H., Fujita T., Furuichi T., Ito K., Inoue K., Yamana K., Zanma A., Takada K., Ito Y., and Komori T. Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog. Genes Dev. 18 (2004) 952-963
224. Zehentner B.K., Dony C., and Burtscher H. The transcription factor Sox9 is involved in BMP2 signaling. J. Bone Miner. Res. 14 (1999) 1734-1741
225. Zhang D., Ferguson C.M., O'Keefe R.J., Puzas J.E., Rosier R.N., and Reynolds P.R. A role for the BMP antagonist chordin in endochondral ossification. J. Bone Miner. Res. 17 (2002) 293-300
226. Zhang D., Schwarz E.M., Rosier R.N., Zuscik M.J., Puzas J.E., and O'Keefe R.J. ALK2 functions as a BMP type I receptor and induces Indian hedgehog in chondrocytes during skeletal development. J. Bone Miner. Res. 18 (2003) 1593-1604
227. Zhang J., Tan X., Li W., Wang Y., Wang J., Cheng X., and Yang X. Smad4 is required for the normal organization of the cartilage growth plate. Dev. Biol. 284 (2005) 311-322
228. Zhang R., Murakami S., Coustry F., Wang Y., and de Crombrugghe B. Constitutive activation of MKK6 in chondrocytes of transgenic mice inhibits proliferation and delays endochondral bone formation. Proc. Natl. Acad. Sci. USA 103 (2006) 365-370
229. Zheng Q., Zhou G., Morello R., Chen Y., Garcia-Rojas X., and Lee B. Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte-specific expression in-vivo. J. Cell Biol. 162 (2003) 833-842
230. Zou H., Wieser R., Massague J., and Niswander L. Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage. Genes Dev. 11 (1997) 2191-2203
231. Zuscik M.J., Baden J.F., Wu Q., Sheu T.J., Schwarz E.M., Drissi H., O'Keefe R.J., Puzas J.E., and Rosier R.N. 5-Azacytidine alters TGF-beta and BMP signaling and induces maturation in articular chondrocytes. J. Cell. Biochem. 92 (2004) 316-331
232. Zuzarte-Luis V., Montero J.A., Rodriguez-Leon J., Merino R., Rodriguez-Rey J.C., and Hurle J.M. A new role for BMP5 during limb development acting through the synergic activation of Smad and MAPK pathways. Dev. Biol. 272 (2004) 39-52