Bone Morphogenetic Protein (BMP) signaling in development and human diseases

Genes and Diseases

Volumn 1, Issue 1, 2014, Pages 87-105

  Wang, Richard N ^a,b   Green, Jordan ^a,b   Wang, Zhongliang ^b,c   Deng, Youlin ^b,c   Qiao, Min ^b,c   Peabody, Michael ^b   Zhang, Qian ^b,c   Ye, Jixing ^b,d   Yan, Zhengjian ^b,c   Denduluri, Sahitya ^a,b   Idowu, Olumuyiwa ^a,b   Li, Melissa ^b   Shen, Christine ^b   Hu, Alan ^b   Haydon, Rex C ^b   Kang, Richard ^b   Mok, James ^b   Lee, Michael J ^b   Luu, Hue L ^b   Shi, Lewis L ^b  

^a UNIVERSITY OF CHICAGO   (United States)

^b UNIVERSITY OF CHICAGO MEDICAL CENTER   (United States)

^c CHONGQING MEDICAL UNIVERSITY   (China)

^d CHONGQING UNIVERSITY   (China)

Author keywords

BMP signaling; Development; Genetics; Mouse knockout; Pathogenesis; Signal transduction

Indexed keywords

BONE MORPHOGENETIC PROTEIN; TRANSFORMING GROWTH FACTOR;

ADIPOGENESIS; BARRETT ESOPHAGUS; COLORECTAL CANCER; EMBRYO DEVELOPMENT; GASTROINTESTINAL TRACT; HOMEOSTASIS; HUMAN; NONHUMAN; OSSIFICATION; OSTEOARTHRITIS; OSTEOGENESIS IMPERFECTA; POLYPOSIS; PROTEIN FAMILY; PROTEIN FUNCTION; RENDU OSLER WEBER DISEASE; REVIEW; SIGNAL TRANSDUCTION; SKELETON; URINARY TRACT;

EID: 84931827012     PISSN: None     EISSN: 23523042     Source Type: Journal    
DOI: 10.1016/j.gendis.2014.07.005     Document Type: Review

References (275)

1. Urist M.R. Bone: formation by autoinduction. Science 1965, 150(3698):893-899.
2. Wozney J.M., Rosen V., Celeste A.J., et al. Novel regulators of bone formation: molecular clones and activities. Science 1988, 242(4885):1528-1534.
3. Hemmati-Brivanlou A., Thomsen G.H. Ventral mesodermal patterning in Xenopus embryos: expression patterns and activities of BMP-2 and BMP-4. Dev Genet 1995, 17(1):78-89.
4. Zou H., Niswander L. Requirement for BMP signaling in interdigital apoptosis and scale formation. Science 1996, 272(5262):738-741.
5. Stewart A., Guan H., Yang K. BMP-3 promotes mesenchymal stem cell proliferation through the TGF-beta/activin signaling pathway. J Cell Physiol 2010, 223(3):658-666.
6. Kobayashi T., Lyons K.M., McMahon A.P., Kronenberg H.M. BMP signaling stimulates cellular differentiation at multiple steps during cartilage development. Proc Natl Acad Sci U S A 2005, 102(50):18023-18027.
7. Bobacz K., Gruber R., Soleiman A., Erlacher L., Smolen J.S., Graninger W.B. Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro. Arthritis Rheum 2003, 48(9):2501-2508.
8. Tsuji K., Bandyopadhyay A., Harfe B.D., et al. BMP2 activity, although dispensable for bone formation, is required for the initiation of fracture healing. Nat Genet 2006, 38(12):1424-1429.
9. Huang Z., Wang D., Ihida-Stansbury K., Jones P.L., Martin J.F. Defective pulmonary vascular remodeling in Smad8 mutant mice. Hum Mol Genet 2009, 18(15):2791-2801.
10. Wagner D.O., Sieber C., Bhushan R., Börgermann J.H., Graf D., Knaus P. BMPs: from bone to body morphogenetic proteins. Sci Signal 2010, 3(107). mr1.
11. Harrison C.A., Al-Musawi S.L., Walton K.L. Prodomains regulate the synthesis, extracellular localisation and activity of TGF-β superfamily ligands. Growth Factors Chur Switz 2011, 29(5):174-186.
12. Heldin C.H., Miyazono K., ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997, 390(6659):465-471.
13. Horbelt D., Denkis A., Knaus P. A portrait of transforming growth factor β superfamily signalling: background matters. Int J Biochem Cell Biol 2012, 44(3):469-474.
14. De Caestecker M. The transforming growth factor-beta superfamily of receptors. Cytokine Growth Factor Rev 2004, 15(1):1-11.
15. Nohe A., Hassel S., Ehrlich M., et al. The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways. J Biol Chem 2002, 277(7):5330-5338.
16. Heldin C.-H., Moustakas A. Role of Smads in TGFβ signaling. Cell Tissue Res 2012, 347(1):21-36.
17. Derynck R., Zhang Y.E. Smad-dependent and Smad-independent pathways in TGF-beta family signalling. Nature 2003, 425(6958):577-584.
18. Yamaguchi K., Shirakabe K., Shibuya H., et al. Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction. Science 1995, 270(5244):2008-2011.
19. Zhang Y.E. Non-Smad pathways in TGF-beta signaling. Cell Res 2009, 19(1):128-139.
20. Broege A., Pham L., Jensen E.D., et al. Bone morphogenetic proteins signal via SMAD and mitogen-activated protein (MAP) kinase pathways at distinct times during osteoclastogenesis. J Biol Chem 2013, 288(52):37230-37240.
21. Corradini E., Babitt J.L., Lin H.Y. The RGM/DRAGON family of BMP co-receptors. Cytokine Growth Factor Rev 2009, 20(5-6):389-398.
22. Walsh D.W., Godson C., Brazil D.P., Martin F. Extracellular BMP-antagonist regulation in development and disease: tied up in knots. Trends Cell Biol 2010, 20(5):244-256.
23. Yao D., Doré J.J., Leof E.B. FKBP12 is a negative regulator of transforming growth factor-beta receptor internalization. J Biol Chem 2000, 275(17):13149-13154.
24. Toporsian M., Jerkic M., Zhou Y.-Q., et al. Spontaneous adult-onset pulmonary arterial hypertension attributable to increased endothelial oxidative stress in a murine model of hereditary hemorrhagic telangiectasia. Arterioscler Thromb Vasc Biol 2010, 30(3):509-517.
25. Mueller T.D., Nickel J. Promiscuity and specificity in BMP receptor activation. FEBS Lett 2012, 586(14):1846-1859.
26. Kessler E., Takahara K., Biniaminov L., Brusel M., Greenspan D.S. Bone morphogenetic protein-1: the type I procollagen C-proteinase. Science 1996, 271(5247):360-362.
27. Shen B., Bhargav D., Wei A., et al. BMP-13 emerges as a potential inhibitor of bone formation. Int J Biol Sci 2009, 5(2):192-200.
28. Daluiski A., Engstrand T., Bahamonde M.E., et al. Bone morphogenetic protein-3 is a negative regulator of bone density. Nat Genet 2001, 27(1):84-88.
29. Luu H.H., Song W.-X., Luo X., et al. Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells. J Orthop Res Off Publ Orthop Res Soc 2007, 25(5):665-677.
30. Shu B., Zhang M., Xie R., et al. BMP2, but not BMP4, is crucial for chondrocyte proliferation and maturation during endochondral bone development. J Cell Sci 2011, 124(Pt 20):3428-3440.
31. Selever J., Liu W., Lu M.-F., Behringer R.R., Martin J.F. Bmp4 in limb bud mesoderm regulates digit pattern by controlling AER development. Dev Biol 2004, 276(2):268-279.
32. Asai-Coakwell M., French C.R., Berry K.M., et al. GDF6, a novel locus for a spectrum of ocular developmental anomalies. Am J Hum Genet 2007, 80(2):306-315.
33. Zhao G.Q., Liaw L., Hogan B.L. Bone morphogenetic protein 8A plays a role in the maintenance of spermatogenesis and the integrity of the epididymis. Dev Camb Engl 1998, 125(6):1103-1112.
34. Settle S., Marker P., Gurley K., et al. The BMP family member Gdf7 is required for seminal vesicle growth, branching morphogenesis, and cytodifferentiation. Dev Biol 2001, 234(1):138-150.
35. Otsuka F., Yao Z., Lee T., Yamamoto S., Erickson G.F., Shimasaki S. Bone morphogenetic protein-15. Identification of target cells and biological functions. J Biol Chem 2000, 275(50):39523-39528.
36. Suzuki N., Labosky P.A., Furuta Y., et al. Failure of ventral body wall closure in mouse embryos lacking a procollagen C-proteinase encoded by Bmp1, a mammalian gene related to Drosophila tolloid. Dev Camb Engl 1996, 122(11):3587-3595.
37. Zhang H., Bradley A. Mice deficient for BMP2 are nonviable and have defects in amnion/chorion and cardiac development. Dev Camb Engl 1996, 122(10):2977-2986.
38. Rivera-Feliciano J., Tabin C.J. Bmp2 instructs cardiac progenitors to form the heart-valve-inducing field. Dev Biol 2006, 295(2):580-588.
39. Ma L., Lu M.-F., Schwartz R.J., Martin J.F. Bmp2 is essential for cardiac cushion epithelial-mesenchymal transition and myocardial patterning. Dev Camb Engl 2005, 132(24):5601-5611.
40. Winnier G., Blessing M., Labosky P.A., Hogan B.L. Bone morphogenetic protein-4 is required for mesoderm formation and patterning in the mouse. Genes Dev 1995, 9(17):2105-2116.
41. Lawson K.A., Dunn N.R., Roelen B.A., et al. Bmp4 is required for the generation of primordial germ cells in the mouse embryo. Genes Dev 1999, 13(4):424-436.
42. De Sousa Lopes S.M.C., Roelen B.A.J., Monteiro R.M., et al. BMP signaling mediated by ALK2 in the visceral endoderm is necessary for the generation of primordial germ cells in the mouse embryo. Genes Dev 2004, 18(15):1838-1849.
43. Furuta Y., Hogan B.L. BMP4 is essential for lens induction in the mouse embryo. Genes Dev 1998, 12(23):3764-3775.
44. Dunn N.R., Winnier G.E., Hargett L.K., Schrick J.J., Fogo A.B., Hogan B.L. Haploinsufficient phenotypes in Bmp4 heterozygous null mice and modification by mutations in Gli3 and Alx4. Dev Biol 1997, 188(2):235-247.
45. Jiao K., Kulessa H., Tompkins K., et al. An essential role of Bmp4 in the atrioventricular septation of the mouse heart. Genes Dev 2003, 17(19):2362-2367.
46. Goldman D.C., Bailey A.S., Pfaffle D.L., Al Masri A., Christian J.L. Fleming WH. BMP4 regulates the hematopoietic stem cell niche. Blood 2009, 114(20):4393-4401.
47. Qian S.-W., Tang Y., Li X., et al. BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis. Proc Natl Acad Sci U S A 2013, 110(9):E798-E807.
48. Li Y., Gordon J., Manley N.R., Litingtung Y., Chiang C. Bmp4 is required for tracheal formation: a novel mouse model for tracheal agenesis. Dev Biol 2008, 322(1):145-155.
49. Liu W., Selever J., Wang D., et al. Bmp4 signaling is required for outflow-tract septation and branchial-arch artery remodeling. Proc Natl Acad Sci U S A 2004, 101(13):4489-4494.
50. Liu W., Selever J., Murali D., et al. Threshold-specific requirements for Bmp4 in mandibular development. Dev Biol 2005, 283(2):282-293.
51. Chang W., Lin Z., Kulessa H., Hebert J., Hogan B.L.M., Wu D.K. Bmp4 is essential for the formation of the vestibular apparatus that detects angular head movements. PLoS Genet 2008, 4(4):e1000050.
52. Kingsley D.M., Bland A.E., Grubber J.M., et al. The mouse short ear skeletal morphogenesis locus is associated with defects in a bone morphogenetic member of the TGF beta superfamily. Cell 1992, 71(3):399-410.
53. Mikić B., van der Meulen M.C., Kingsley D.M., Carter D.R. Long bone geometry and strength in adult BMP-5 deficient mice. Bone 1995, 16(4):445-454.
54. Solloway M.J., Dudley A.T., Bikoff E.K., Lyons K.M., Hogan B.L., Robertson E.J. Mice lacking Bmp6 function. Dev Genet 1998, 22(4):321-339.
55. Perry M.J., McDougall K.E., Hou S.-C., Tobias J.H. Impaired growth plate function in bmp-6 null mice. Bone 2008, 42(1):216-225.
56. Sugiura K., Su Y.-Q., Eppig J.J. Does bone morphogenetic protein 6 (BMP6) affect female fertility in the mouse?. Biol Reprod 2010, 83(6):997-1004.
57. Dudley A.T., Lyons K.M., Robertson E.J. A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev 1995, 9(22):2795-2807.
58. Luo G., Hofmann C., Bronckers A.L., Sohocki M., Bradley A., Karsenty G. BMP-7 is an inducer of nephrogenesis, and is also required for eye development and skeletal patterning. Genes Dev 1995, 9(22):2808-2820.
59. Segklia A., Seuntjens E., Elkouris M., et al. Bmp7 regulates the survival, proliferation, and neurogenic properties of neural progenitor cells during corticogenesis in the mouse. PloS One 2012, 7(3):e34088.
60. Tseng Y.-H., Kokkotou E., Schulz T.J., et al. New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 2008, 454(7207):1000-1004.
61. Yasmin N., Bauer T., Modak M., et al. Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation. J Exp Med 2013, 210(12):2597-2610.
62. Tomita M., Asada M., Asada N., et al. Bmp7 maintains undifferentiated kidney progenitor population and determines nephron numbers at birth. PloS One 2013, 8(8):e73554.
63. Tsuji K., Cox K., Gamer L., Graf D., Economides A., Rosen V. Conditional deletion of BMP7 from the limb skeleton does not affect bone formation or fracture repair. J Orthop Res Off Publ Orthop Res Soc 2010, 28(3):384-389.
64. Kazama I., Mahoney Z., Miner J.H., Graf D., Economides A.N., Kreidberg J.A. Podocyte-derived BMP7 is critical for nephron development. J Am Soc Nephrol JASN 2008, 19(11):2181-2191.
65. Ying Y., Liu X.M., Marble A., Lawson K.A., Zhao G.Q. Requirement of Bmp8b for the generation of primordial germ cells in the mouse. Mol Endocrinol Balt Md 2000, 14(7):1053-1063.
66. Zhao G.Q., Deng K., Labosky P.A., Liaw L., Hogan B.L. The gene encoding bone morphogenetic protein 8B is required for the initiation and maintenance of spermatogenesis in the mouse. Genes Dev 1996, 10(13):1657-1669.
67. Levet S., Ciais D., Merdzhanova G., et al. Bone morphogenetic protein 9 (BMP9) controls lymphatic vessel maturation and valve formation. Blood 2013, 122(4):598-607.
68. Yoshimatsu Y., Lee Y.G., Akatsu Y., et al. Bone morphogenetic protein-9 inhibits lymphatic vessel formation via activin receptor-like kinase 1 during development and cancer progression. Proc Natl Acad Sci U S A 2013, 110(47):18940-18945.
69. Chen H., Shi S., Acosta L., et al. BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Dev Camb Engl 2004, 131(9):2219-2231.
70. McPherron A.C., Lawler A.M., Lee S.J. Regulation of anterior/posterior patterning of the axial skeleton by growth/differentiation factor 11. Nat Genet 1999, 22(3):260-264.
71. Dichmann D.S., Yassin H., Serup P. Analysis of pancreatic endocrine development in GDF11-deficient mice. Dev Dyn Off Publ Am Assoc Anat 2006, 235(11):3016-3025.
72. Harmon E.B., Apelqvist A.A., Smart N.G., Gu X., Osborne D.H., Kim S.K. GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas development. Dev Camb Engl 2004, 131(24):6163-6174.
73. Esquela A.F., Lee S.-J. Regulation of metanephric kidney development by growth/differentiation factor 11. Dev Biol 2003, 257(2):356-370.
74. Shi Y., Liu J.-P. Gdf11 facilitates temporal progression of neurogenesis in the developing spinal cord. J Neurosci Off J Soc Neurosci 2011, 31(3):883-893.
75. Wu H.-H., Ivkovic S., Murray R.C., et al. Autoregulation of neurogenesis by GDF11. Neuron 2003, 37(2):197-207.
76. Kim J., Wu H.-H., Lander A.D., Lyons K.M., Matzuk M.M., Calof A.L. GDF11 controls the timing of progenitor cell competence in developing retina. Science 2005, 308(5730):1927-1930.
77. Mikic B., Ferreira M.P., Battaglia T.C., Hunziker E.B. Accelerated hypertrophic chondrocyte kinetics in GDF-7 deficient murine tibial growth plates. J Orthop Res Off Publ Orthop Res Soc 2008, 26(7):986-990.
78. Maloul A., Rossmeier K., Mikic B., Pogue V., Battaglia T. Geometric and material contributions to whole bone structural behavior in GDF-7-deficient mice. Connect Tissue Res 2006, 47(3):157-162.
79. Mikic B., Entwistle R., Rossmeier K., Bierwert L. Effect of GDF-7 deficiency on tail tendon phenotype in mice. J Orthop Res Off Publ Orthop Res Soc 2008, 26(6):834-839.
80. Mikic B., Bierwert L., Tsou D. Achilles tendon characterization in GDF-7 deficient mice. J Orthop Res Off Publ Orthop Res Soc 2006, 24(4):831-841.
81. Lee K.J., Mendelsohn M., Jessell T.M. Neuronal patterning by BMPs: a requirement for GDF7 in the generation of a discrete class of commissural interneurons in the mouse spinal cord. Genes Dev 1998, 12(21):3394-3407.
82. Settle S.H., Rountree R.B., Sinha A., Thacker A., Higgins K., Kingsley D.M. Multiple joint and skeletal patterning defects caused by single and double mutations in the mouse Gdf6 and Gdf5 genes. Dev Biol 2003, 254(1):116-130.
83. Clendenning D.E., Mortlock D.P. The BMP ligand Gdf6 prevents differentiation of coronal suture mesenchyme in early cranial development. PloS One 2012, 7(5):e36789.
84. Asai-Coakwell M., March L., Dai X.H., et al. Contribution of growth differentiation factor 6-dependent cell survival to early-onset retinal dystrophies. Hum Mol Genet 2013, 22(7):1432-1442.
85. Hanel M.L., Hensey C. Eye and neural defects associated with loss of GDF6. BMC Dev Biol 2006, 6:43.
86. Tassabehji M., Fang Z.M., Hilton E.N., et al. Mutations in GDF6 are associated with vertebral segmentation defects in Klippel-Feil syndrome. Hum Mutat 2008, 29(8):1017-1027.
87. Mikic B., Rossmeier K., Bierwert L. Identification of a tendon phenotype in GDF6 deficient mice. Anat Rec Hoboken 2009, 292(3):396-400.
88. Mikic B., Rossmeier K., Bierwert L. Sexual dimorphism in the effect of GDF-6 deficiency on murine tendon. J Orthop Res Off Publ Orthop Res Soc 2009, 27(12):1603-1611.
89. Storm E.E., Huynh T.V., Copeland N.G., Jenkins N.A., Kingsley D.M., Lee S.J. Limb alterations in brachypodism mice due to mutations in a new member of the TGF beta-superfamily. Nature 1994, 368(6472):639-643.
90. Storm E.E., Kingsley D.M. GDF5 coordinates bone and joint formation during digit development. Dev Biol 1999, 209(1):11-27.
91. Chhabra A., Zijerdi D., Zhang J., Kline A., Balian G., Hurwitz S. BMP-14 deficiency inhibits long bone fracture healing: a biochemical, histologic, and radiographic assessment. J Orthop Trauma 2005, 19(9):629-634.
92. Coleman C.M., Scheremeta B.H., Boyce A.T., Mauck R.L., Tuan R.S. Delayed fracture healing in growth differentiation factor 5-deficient mice: a pilot study. Clin Orthop 2011, 469(10):2915-2924.
93. Masuya H., Nishida K., Furuichi T., et al. A novel dominant-negative mutation in Gdf5 generated by ENU mutagenesis impairs joint formation and causes osteoarthritis in mice. Hum Mol Genet 2007, 16(19):2366-2375.
94. Mikic B., Schalet B.J., Clark R.T., Gaschen V., Hunziker E.B. GDF-5 deficiency in mice alters the ultrastructure, mechanical properties and composition of the Achilles tendon. J Orthop Res Off Publ Orthop Res Soc 2001, 19(3):365-371.
95. Zaidi S.H.E., Huang Q., Momen A., Riazi A., Husain M. Growth differentiation factor 5 regulates cardiac repair after myocardial infarction. J Am Coll Cardiol 2010, 55(2):135-143.
96. Battaglia T.C. GDF-5 deficiency alters stress-relaxation properties in mouse skin. J Dermatol Sci 2005, 39(3):192-195.
97. Yan C., Wang P., DeMayo J., et al. Synergistic roles of bone morphogenetic protein 15 and growth differentiation factor 9 in ovarian function. Mol Endocrinol Balt Md 2001, 15(6):854-866.
98. Lechleider R.J., Ryan J.L., Garrett L., et al. Targeted mutagenesis of Smad1 reveals an essential role in chorioallantoic fusion. Dev Biol 2001, 240(1):157-167.
99. Tremblay K.D., Dunn N.R., Robertson E.J. Mouse embryos lacking Smad1 signals display defects in extra-embryonic tissues and germ cell formation. Dev Camb Engl 2001, 128(18):3609-3621.
100. Hayashi K., Kobayashi T., Umino T., Goitsuka R., Matsui Y., Kitamura D. SMAD1 signaling is critical for initial commitment of germ cell lineage from mouse epiblast. Mech Dev 2002, 118(1-2):99-109.
101. Wang M., Jin H., Tang D., Huang S., Zuscik M.J., Chen D. Smad1 plays an essential role in bone development and postnatal bone formation. Osteoarthr Cartil OARS Osteoarthr Res Soc 2011, 19(6):751-762.
102. Xu B., Chen C., Chen H., et al. Smad1 and its target gene Wif1 coordinate BMP and Wnt signaling activities to regulate fetal lung development. Dev Camb Engl 2011, 138(5):925-935.
103. Chang H., Huylebroeck D., Verschueren K., Guo Q., Matzuk M.M., Zwijsen A. Smad5 knockout mice die at mid-gestation due to multiple embryonic and extraembryonic defects. Dev Camb Engl 1999, 126(8):1631-1642.
104. Chang H., Matzuk M.M. Smad5 is required for mouse primordial germ cell development. Mech Dev 2001, 104(1-2):61-67.
105. Chang H., Zwijsen A., Vogel H., Huylebroeck D., Matzuk M.M. Smad5 is essential for left-right asymmetry in mice. Dev Biol 2000, 219(1):71-78.
106. Arnold S.J., Maretto S., Islam A., Bikoff E.K., Robertson E.J. Dose-dependent Smad1, Smad5 and Smad8 signaling in the early mouse embryo. Dev Biol 2006, 296(1):104-118.
107. Sirard C., de la Pompa J.L., Elia A., et al. The tumor suppressor gene Smad4/Dpc4 is required for gastrulation and later for anterior development of the mouse embryo. Genes Dev 1998, 12(1):107-119.
108. Takaku K., Miyoshi H., Matsunaga A., Oshima M., Sasaki N., Taketo M.M. Gastric and duodenal polyps in Smad4 (Dpc4) knockout mice. Cancer Res 1999, 59(24):6113-6117.
109. Taketo M.M., Takaku K. Gastro-intestinal tumorigenesis in Smad4 mutant mice. Cytokine Growth Factor Rev 2000, 11(1-2):147-157.
110. Pan D., Schomber T., Kalberer C.P., et al. Normal erythropoiesis but severe polyposis and bleeding anemia in Smad4-deficient mice. Blood 2007, 110(8):3049-3055.
111. Tan X., Weng T., Zhang J., et al. Smad4 is required for maintaining normal murine postnatal bone homeostasis. J Cell Sci 2007, 120(Pt 13):2162-2170.
112. Yang S., Hou Z., Yang G., et al. Chondrocyte-specific Smad4 gene conditional knockout results in hearing loss and inner ear malformation in mice. Dev Dyn Off Publ Am Assoc Anat 2009, 238(8):1897-1908.
113. Yang S., Deng A., Huang D., et al. The role of Smad4 in vestibular development in mice. Int J Dev Neurosci Off J Int Soc Dev Neurosci 2011, 29(1):15-23.
114. Zhang J., Tan X., Li W., et al. Smad4 is required for the normal organization of the cartilage growth plate. Dev Biol 2005, 284(2):311-322.
115. Sartori R., Schirwis E., Blaauw B., et al. BMP signaling controls muscle mass. Nat Genet 2013, 45(11):1309-1318.
116. Wang J., Xu N., Feng X., et al. Targeted disruption of Smad4 in cardiomyocytes results in cardiac hypertrophy and heart failure. Circ Res 2005, 97(8):821-828.
117. Lan Y., Liu B., Yao H., et al. Essential role of endothelial Smad4 in vascular remodeling and integrity. Mol Cell Biol 2007, 27(21):7683-7692.
118. Qi X., Yang G., Yang L., et al. Essential role of Smad4 in maintaining cardiomyocyte proliferation during murine embryonic heart development. Dev Biol 2007, 311(1):136-146.
119. Mao X., Debenedittis P., Sun Y., et al. Vascular smooth muscle cell Smad4 gene is important for mouse vascular development. Arterioscler Thromb Vasc Biol 2012, 32(9):2171-2177.
120. Zhou Y.-X., Zhao M., Li D., et al. Cerebellar deficits and hyperactivity in mice lacking Smad4. J Biol Chem 2003, 278(43):42313-42320.
121. Liu Y., Lin D. Necessity of Smad4 for the normal development of the mouse lacrimal gland. Jpn J Ophthalmol 2014, 58(3):298-306.
122. Archambeault D.R., Yao H.H.-C. Loss of smad4 in Sertoli and Leydig cells leads to testicular dysgenesis and hemorrhagic tumor formation in mice. Biol Reprod 2014, 90(3):62.
123. Yu C., Zhang Y.-L., Fan H.-Y. Selective Smad4 knockout in ovarian preovulatory follicles results in multiple defects in ovulation. Mol Endocrinol Balt Md 2013, 27(6):966-978.
124. Pangas S.A., Li X., Robertson E.J., Matzuk M.M. Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice. Mol Endocrinol Balt Md 2006, 20(6):1406-1422.
125. Owens P., Engelking E., Han G., Haeger S.M., Wang X.-J. Epidermal Smad4 deletion results in aberrant wound healing. Am J Pathol 2010, 176(1):122-133.
126. Qiao W., Li A.G., Owens P., Xu X., Wang X.-J., Deng C.-X. Hair follicle defects and squamous cell carcinoma formation in Smad4 conditional knockout mouse skin. Oncogene 2006, 25(2):207-217.
127. Yang L., Li W., Wang S., et al. Smad4 disruption accelerates keratinocyte reepithelialization in murine cutaneous wound repair. Histochem Cell Biol 2012, 138(4):573-582.
128. Bornstein S., White R., Malkoski S., et al. Smad4 loss in mice causes spontaneous head and neck cancer with increased genomic instability and inflammation. J Clin Invest 2009, 119(11):3408-3419.
129. Gao Y., Yang G., Weng T., et al. Disruption of Smad4 in odontoblasts causes multiple keratocystic odontogenic tumors and tooth malformation in mice. Mol Cell Biol 2009, 29(21):5941-5951.
130. Estrada K.D., Retting K.N., Chin A.M., Lyons K.M. Smad6 is essential to limit BMP signaling during cartilage development. J Bone Min Res Off J Am Soc Bone Min Res 2011, 26(10):2498-2510.
131. Galvin K.M., Donovan M.J., Lynch C.A., et al. A role for smad6 in development and homeostasis of the cardiovascular system. Nat Genet 2000, 24(2):171-174.
132. Chen Q., Chen H., Zheng D., et al. Smad7 is required for the development and function of the heart. J Biol Chem 2009, 284(1):292-300.
133. Estrada K.D., Wang W., Retting K.N., et al. Smad7 regulates terminal maturation of chondrocytes in the growth plate. Dev Biol 2013, 382(2):375-384.
134. Tojo M., Takebe A., Takahashi S., et al. Smad7-deficient mice show growth retardation with reduced viability. J Biochem (Tokyo) 2012, 151(6):621-631.
135. Chung A.C.K., Huang X.R., Zhou L., Heuchel R., Lai K.N., Lan H.Y. Disruption of the Smad7 gene promotes renal fibrosis and inflammation in unilateral ureteral obstruction (UUO) in mice. Nephrol Dial Transpl Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc 2009, 24(5):1443-1454.
136. Zhang R., Huang H., Cao P., Wang Z., Chen Y., Pan Y. Sma- and Mad-related protein 7 (Smad7) is required for embryonic eye development in the mouse. J Biol Chem 2013, 288(15):10275-10285.
137. Dong C., Zhu S., Wang T., et al. Deficient Smad7 expression: a putative molecular defect in scleroderma. Proc Natl Acad Sci U S A 2002, 99(6):3908-3913.
138. Li R., Rosendahl A., Brodin G., et al. Deletion of exon I of SMAD7 in mice results in altered B cell responses. J Immunol Balt Md 2006, 176(11):6777-6784.
139. Kleiter I., Song J., Lukas D., et al. Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis. Brain J Neurol 2010, 133(Pt 4):1067-1081.
140. Mishina Y., Suzuki A., Ueno N., Behringer R.R. Bmpr encodes a type I bone morphogenetic protein receptor that is essential for gastrulation during mouse embryogenesis. Genes Dev 1995, 9(24):3027-3037.
141. Park C., Lavine K., Mishina Y., Deng C.-X., Ornitz D.M., Choi K. Bone morphogenetic protein receptor 1A signaling is dispensable for hematopoietic development but essential for vessel and atrioventricular endocardial cushion formation. Dev Camb Engl 2006, 133(17):3473-3484.
142. Sun J., Liu Y.-H., Chen H., et al. Deficient Alk3-mediated BMP signaling causes prenatal omphalocele-like defect. Biochem Biophys Res Commun 2007, 360(1):238-243.
143. Kamiya N., Ye L., Kobayashi T., et al. BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway. Dev Camb Engl 2008, 135(22):3801-3811.
144. Jing J., Ren Y., Zong Z., et al. BMP receptor 1A determines the cell fate of the postnatal growth plate. Int J Biol Sci 2013, 9(9):895-906.
145. Steinbicker A.U., Bartnikas T.B., Lohmeyer L.K., et al. Perturbation of hepcidin expression by BMP type I receptor deletion induces iron overload in mice. Blood 2011, 118(15):4224-4230.
146. Gaussin V., Van de Putte T., Mishina Y., et al. Endocardial cushion and myocardial defects after cardiac myocyte-specific conditional deletion of the bone morphogenetic protein receptor ALK3. Proc Natl Acad Sci U S A 2002, 99(5):2878-2883.
147. Gaussin V., Morley G.E., Cox L., et al. Alk3/Bmpr1a receptor is required for development of the atrioventricular canal into valves and annulus fibrosus. Circ Res 2005, 97(3):219-226.
148. Song L., Fässler R., Mishina Y., Jiao K., Baldwin H.S. Essential functions of Alk3 during AV cushion morphogenesis in mouse embryonic hearts. Dev Biol 2007, 301(1):276-286.
149. El-Bizri N., Guignabert C., Wang L., et al. SM22alpha-targeted deletion of bone morphogenetic protein receptor 1A in mice impairs cardiac and vascular development, and influences organogenesis. Dev Camb Engl 2008, 135(17):2981-2991.
150. El-Bizri N., Wang L., Merklinger S.L., et al. Smooth muscle protein 22alpha-mediated patchy deletion of Bmpr1a impairs cardiac contractility but protects against pulmonary vascular remodeling. Circ Res 2008, 102(3):380-388.
151. Eblaghie M.C., Reedy M., Oliver T., Mishina Y., Hogan B.L.M. Evidence that autocrine signaling through Bmpr1a regulates the proliferation, survival and morphogenetic behavior of distal lung epithelial cells. Dev Biol 2006, 291(1):67-82.
152. Sun J., Chen H., Chen C., et al. Prenatal lung epithelial cell-specific abrogation of Alk3-bone morphogenetic protein signaling causes neonatal respiratory distress by disrupting distal airway formation. Am J Pathol 2008, 172(3):571-582.
153. Hartwig S., Bridgewater D., Di Giovanni V., Cain J., Mishina Y., Rosenblum N.D. BMP receptor ALK3 controls collecting system development. J Am Soc Nephrol JASN 2008, 19(1):117-124.
154. Peng C.-Y., Mukhopadhyay A., Jarrett J.C., Yoshikawa K., Kessler J.A. BMP receptor 1A regulates development of hypothalamic circuits critical for feeding behavior. J Neurosci Off J Soc Neurosci 2012, 32(48):17211-17224.
155. Zhao Q., Zhao J.-Y., Wu D., Lu X.-C., Zhang J.-S., Zhang Z.-Y. Mutually inductive interactions between the lens and retina require ALK3 functions during mouse embryonic development. Int J Ophthalmol 2012, 5(2):119-124.
156. Wu X., Zhang N., Lee M.M. Mullerian inhibiting substance recruits ALK3 to regulate Leydig cell differentiation. Endocrinology 2012, 153(10):4929-4937.
157. Edson M.A., Nalam R.L., Clementi C., et al. Granulosa cell-expressed BMPR1A and BMPR1B have unique functions in regulating fertility but act redundantly to suppress ovarian tumor development. Mol Endocrinol Balt Md 2010, 24(6):1251-1266.
158. Liu W., Sun X., Braut A., et al. Distinct functions for Bmp signaling in lip and palate fusion in mice. Dev Camb Engl 2005, 132(6):1453-1461.
159. Yuhki M., Yamada M., Kawano M., et al. BMPR1A signaling is necessary for hair follicle cycling and hair shaft differentiation in mice. Dev Camb Engl 2004, 131(8):1825-1833.
160. Yang Z., Hai B., Qin L., et al. Cessation of epithelial Bmp signaling switches the differentiation of crown epithelia to the root lineage in a β-catenin-dependent manner. Mol Cell Biol 2013, 33(23):4732-4744.
161. Yi S.E., Daluiski A., Pederson R., Rosen V., Lyons K.M. The type I BMP receptor BMPRIB is required for chondrogenesis in the mouse limb. Dev Camb Engl 2000, 127(3):621-630.
162. Liu J., Wilson S., Reh T. BMP receptor 1b is required for axon guidance and cell survival in the developing retina. Dev Biol 2003, 256(1):34-48.
163. Yi S.E., LaPolt P.S., Yoon B.S., Chen J.Y., Lu J.K., Lyons K.M. The type I BMP receptor BmprIB is essential for female reproductive function. Proc Natl Acad Sci U S A 2001, 98(14):7994-7999.
164. Komatsu Y., Scott G., Nagy A., Kaartinen V., Mishina Y. BMP type I receptor ALK2 is essential for proper patterning at late gastrulation during mouse embryogenesis. Dev Dyn Off Publ Am Assoc Anat 2007, 236(2):512-517.
165. Rajagopal R., Dattilo L.K., Kaartinen V., et al. Functions of the type 1 BMP receptor Acvr1 (Alk2) in lens development: cell proliferation, terminal differentiation, and survival. Invest Ophthalmol Vis Sci 2008, 49(11):4953-4960.
166. Dudas M., Sridurongrit S., Nagy A., Okazaki K., Kaartinen V. Craniofacial defects in mice lacking BMP type I receptor Alk2 in neural crest cells. Mech Dev 2004, 121(2):173-182.
167. Kaartinen V., Dudas M., Nagy A., Sridurongrit S., Lu M.M., Epstein J.A. Cardiac outflow tract defects in mice lacking ALK2 in neural crest cells. Dev Camb Engl 2004, 131(14):3481-3490.
168. Wang J., Sridurongrit S., Dudas M., et al. Atrioventricular cushion transformation is mediated by ALK2 in the developing mouse heart. Dev Biol 2005, 286(1):299-310.
169. Thomas P.S., Sridurongrit S., Ruiz-Lozano P., Kaartinen V. Deficient signaling via Alk2 (Acvr1) leads to bicuspid aortic valve development. PloS One 2012, 7(4):e35539.
170. Clementi C., Tripurani S.K., Large M.J., et al. Activin-like kinase 2 functions in peri-implantation uterine signaling in mice and humans. PLoS Genet 2013, 9(11):e1003863.
171. Nagashima T., Li Q., Clementi C., Lydon J.P., DeMayo F.J., Matzuk M.M. BMPR2 is required for postimplantation uterine function and pregnancy maintenance. J Clin Invest 2013, 123(6):2539-2550.
172. Beppu H., Kawabata M., Hamamoto T., et al. BMP type II receptor is required for gastrulation and early development of mouse embryos. Dev Biol 2000, 221(1):249-258.
173. Beppu H., Malhotra R., Beppu Y., Lepore J.J., Parmacek M.S., Bloch K.D. BMP type II receptor regulates positioning of outflow tract and remodeling of atrioventricular cushion during cardiogenesis. Dev Biol 2009, 331(2):167-175.
174. Beppu H., Ichinose F., Kawai N., et al. BMPR-II heterozygous mice have mild pulmonary hypertension and an impaired pulmonary vascular remodeling response to prolonged hypoxia. Am J Physiol Lung Cell Mol Physiol 2004, 287(6):L1241-L1247.
175. West J., Harral J., Lane K., et al. Mice expressing BMPR2R899X transgene in smooth muscle develop pulmonary vascular lesions. Am J Physiol Lung Cell Mol Physiol 2008, 295(5):L744-L755.
176. Hong K.-H., Lee Y.J., Lee E., et al. Genetic ablation of the BMPR2 gene in pulmonary endothelium is sufficient to predispose to pulmonary arterial hypertension. Circulation 2008, 118(7):722-730.
177. Matzuk M.M., Kumar T.R., Bradley A. Different phenotypes for mice deficient in either activins or activin receptor type II. Nature 1995, 374(6520):356-360.
178. Ma X., Reyna A., Mani S.K., Matzuk M.M., Kumar T.R. Impaired male sexual behavior in activin receptor type II knockout mice. Biol Reprod 2005, 73(6):1182-1190.
179. Wreford N.G., Rajendra Kumar T., Matzuk M.M., de Kretser D.M. Analysis of the testicular phenotype of the follicle-stimulating hormone beta-subunit knockout and the activin type II receptor knockout mice by stereological analysis. Endocrinology 2001, 142(7):2916-2920.
180. Oh S.P., Li E. The signaling pathway mediated by the type IIB activin receptor controls axial patterning and lateral asymmetry in the mouse. Genes Dev 1997, 11(14):1812-1826.
181. Storm E.E., Kingsley D.M. Joint patterning defects caused by single and double mutations in members of the bone morphogenetic protein (BMP) family. Dev Camb Engl 1996, 122(12):3969-3979.
182. Williams E.S., Uhas K.A., Bunke B.P., Garber K.B., Martin C.L. Cleft palate in a multigenerational family with a microdeletion of 20p12.3 involving BMP2. Am J Med Genet A 2012, 158A(10):2616-2620.
183. Suazo J., Tapia J.C., Santos J.L., Castro V.G., Colombo A., Blanco R. Risk variants in BMP4 promoters for nonsyndromic cleft lip/palate in a Chilean population. BMC Med Genet 2011, 12:163.
184. Kaplan F.S., Le Merrer M., Glaser D.L., et al. Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol 2008, 22(1):191-205.
185. Kaplan F.S., Xu M., Seemann P., et al. Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat 2009, 30(3):379-390.
186. Ohte S., Shin M., Sasanuma H., et al. A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H. Biochem Biophys Res Commun 2011, 407(1):213-218.
187. Fukuda T., Kanomata K., Nojima J., et al. A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor. Biochem Biophys Res Commun 2008, 377(3):905-909.
188. Bagarova J., Vonner A.J., Armstrong K.A., et al. Constitutively active ALK2 receptor mutants require type II receptor cooperation. Mol Cell Biol 2013, 33(12):2413-2424.
189. Le V.Q., Wharton K.A. Hyperactive BMP signaling induced by ALK2(R206H) requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva. Dev Dyn Off Publ Am Assoc Anat 2012, 241(1):200-214.
190. Chaikuad A., Alfano I., Kerr G., et al. Structure of the bone morphogenetic protein receptor ALK2 and implications for fibrodysplasia ossificans progressiva. J Biol Chem 2012, 287(44):36990-36998.
191. Shen Q., Little S.C., Xu M., et al. The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization. J Clin Invest 2009, 119(11):3462-3472.
192. Song G.-A., Kim H.-J., Woo K.-M., et al. Molecular consequences of the ACVR1(R206H) mutation of fibrodysplasia ossificans progressiva. J Biol Chem 2010, 285(29):22542-22553.
193. Fiori J.L., Billings P.C., de la Peña L.S., Kaplan F.S., Shore E.M. Dysregulation of the BMP-p38 MAPK signaling pathway in cells from patients with fibrodysplasia ossificans progressiva (FOP). J Bone Min Res Off J Am Soc Bone Min Res 2006, 21(6):902-909.
194. Yu P.B., Deng D.Y., Lai C.S., et al. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med 2008, 14(12):1363-1369.
195. Sanvitale C.E., Kerr G., Chaikuad A., et al. A new class of small molecule inhibitor of BMP signaling. PloS One 2013, 8(4):e62721.
196. Shi S., Cai J., de Gorter D.J.J., et al. Antisense-oligonucleotide mediated exon skipping in activin-receptor-like kinase 2: inhibiting the receptor that is overactive in fibrodysplasia ossificans progressiva. PloS One 2013, 8(7):e69096.
197. Marini J.C., Blissett A.R. New genes in bone development: what's new in osteogenesis imperfecta. J Clin Endocrinol Metab 2013, 98(8):3095-3103.
198. Martínez-Glez V., Valencia M., Caparrós-Martín J.A., et al. Identification of a mutation causing deficient BMP1/mTLD proteolytic activity in autosomal recessive osteogenesis imperfecta. Hum Mutat 2012, 33(2):343-350.
199. Hopkins D.R., Keles S., Greenspan D.S. The bone morphogenetic protein 1/Tolloid-like metalloproteinases. Matrix Biol J Int Soc Matrix Biol 2007, 26(7):508-523.
200. Asharani P.V., Keupp K., Semler O., et al. Attenuated BMP1 function compromises osteogenesis, leading to bone fragility in humans and zebrafish. Am J Hum Genet 2012, 90(4):661-674.
201. Wilkins J.M., Southam L., Mustafa Z., Chapman K., Loughlin J. Association of a functional microsatellite within intron 1 of the BMP5 gene with susceptibility to osteoarthritis. BMC Med Genet 2009, 10:141.
202. Southam L., Dowling B., Ferreira A., et al. Microsatellite association mapping of a primary osteoarthritis susceptibility locus on chromosome 6p12.3-q13. Arthritis Rheum 2004, 50(12):3910-3914.
203. Miyamoto Y., Mabuchi A., Shi D., et al. A functional polymorphism in the 5' UTR of GDF5 is associated with susceptibility to osteoarthritis. Nat Genet 2007, 39(4):529-533.
204. Nakase T., Miyaji T., Tomita T., et al. Localization of bone morphogenetic protein-2 in human osteoarthritic cartilage and osteophyte. Osteoarthr Cartil OARS Osteoarthr Res Soc 2003, 11(4):278-284.
205. Papathanasiou I., Malizos K.N., Tsezou A. Bone morphogenetic protein-2-induced Wnt/β-catenin signaling pathway activation through enhanced low-density-lipoprotein receptor-related protein 5 catabolic activity contributes to hypertrophy in osteoarthritic chondrocytes. Arthritis Res Ther 2012, 14(2):R82.
206. Albilia J.B., Tenenbaum H.C., Clokie C.M.L., et al. Serum levels of BMP-2, 4, 7 and AHSG in patients with degenerative joint disease requiring total arthroplasty of the hip and temporomandibular joints. J Orthop Res Off Publ Orthop Res Soc 2013, 31(1):44-52.
207. Bijsterbosch J., Kloppenburg M., Reijnierse M., et al. Association study of candidate genes for the progression of hand osteoarthritis. Osteoarthr Cartil OARS Osteoarthr Res Soc 2013, 21(4):565-569.
208. Badlani N., Oshima Y., Healey R., Coutts R., Amiel D. Use of bone morphogenic protein-7 as a treatment for osteoarthritis. Clin Orthop 2009, 467(12):3221-3229.
209. Hayashi M., Muneta T., Takahashi T., Ju Y.-J., Tsuji K., Sekiya I. Intra-articular injections of bone morphogenetic protein-7 retard progression of existing cartilage degeneration. J Orthop Res Off Publ Orthop Res Soc 2010, 28(11):1502-1506.
210. Hunter D.J., Pike M.C., Jonas B.L., Kissin E., Krop J., McAlindon T. Phase 1 safety and tolerability study of BMP-7 in symptomatic knee osteoarthritis. BMC Musculoskelet Disord 2010, 11(232).
211. Srinivasan P.P., McCoy S.Y., Jha A.K., et al. Injectable perlecan domain 1-hyaluronan microgels potentiate the cartilage repair effect of BMP2 in a murine model of early osteoarthritis. Biomed Mater Bristol Engl 2012, 7(2):024109.
212. Winbanks C.E., Chen J.L., Qian H., et al. The bone morphogenetic protein axis is a positive regulator of skeletal muscle mass. J Cell Biol 2013, 203(2):345-357.
213. Le Goff C., Mahaut C., Abhyankar A., et al. Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Nat Genet 2012, 44(1):85-88.
214. Batts L.E., Polk D.B., Dubois R.N., Kulessa H. Bmp signaling is required for intestinal growth and morphogenesis. Dev Dyn Off Publ Am Assoc Anat 2006, 235(6):1563-1570.
215. Torihashi S., Hattori T., Hasegawa H., Kurahashi M., Ogaeri T., Fujimoto T. The expression and crucial roles of BMP signaling in development of smooth muscle progenitor cells in the mouse embryonic gut. Differ Res Biol Divers 2009, 77(3):277-289.
216. Maloum F., Allaire J.M., Gagné-Sansfaçon J., et al. Epithelial BMP signaling is required for proper specification of epithelial cell lineages and gastric endocrine cells. Am J Physiol Gastrointest Liver Physiol 2011, 300(6):G1065-G1079.
217. Castillo D., Puig S., Iglesias M., et al. Activation of the BMP4 pathway and early expression of CDX2 characterize non-specialized columnar metaplasia in a human model of Barrett's esophagus. J Gastrointest Surg Off J Soc Surg Aliment Tract 2012, 16(2):227-237. discussion 237.
218. Milano F., van Baal J.W.P.M., Buttar N.S., et al. Bone morphogenetic protein 4 expressed in esophagitis induces a columnar phenotype in esophageal squamous cells. Gastroenterology 2007, 132(7):2412-2421.
219. Yamanaka Y., Shiotani A., Fujimura Y., et al. Expression of Sonic hedgehog (SHH) and CDX2 in the columnar epithelium of the lower oesophagus. Dig Liver Dis Off J Ital Soc Gastroenterol Ital Assoc Study Liver 2011, 43(1):54-59.
220. Wang D.H., Clemons N.J., Miyashita T., et al. Aberrant epithelial-mesenchymal Hedgehog signaling characterizes Barrett's metaplasia. Gastroenterology 2010, 138(5):1810-1822.
221. Van Baal J.W.P.M., Verbeek R.E., Bus P., et al. microRNA-145 in Barrett's oesophagus: regulating BMP4 signalling via GATA6. Gut 2013, 62(5):664-675.
222. Jee M.J., Yoon S.M., Kim E.J., et al. A novel germline mutation in exon 10 of the SMAD4 gene in a familial juvenile polyposis. Gut Liver 2013, 7(6):747-751.
223. Howe J.R., Roth S., Ringold J.C., et al. Mutations in the SMAD4/DPC4 gene in juvenile polyposis. Science 1998, 280(5366):1086-1088.
224. Howe J.R., Bair J.L., Sayed M.G., et al. Germline mutations of the gene encoding bone morphogenetic protein receptor 1A in juvenile polyposis. Nat Genet 2001, 28(2):184-187.
225. Carr J.C., Dahdaleh F.S., Wang D., Howe J.R. Germline mutations in SMAD4 disrupt bone morphogenetic protein signaling. J Surg Res 2012, 174(2):211-214.
226. Howe J.R., Dahdaleh F.S., Carr J.C., Wang D., Sherman S.K., Howe J.R. BMPR1A mutations in juvenile polyposis affect cellular localization. J Surg Res 2013, 184(2):739-745.
227. Septer S., Zhang L., Lawson C.E., Cocjin J., Attard T., Ardinger H.H. Aggressive juvenile polyposis in children with chromosome 10q23 deletion. World J Gastroenterol WJG 2013, 19(14):2286-2292.
228. Chau J.F.L., Jia D., Wang Z., et al. A crucial role for bone morphogenetic protein-Smad1 signalling in the DNA damage response. Nat Commun 2012, 3(836).
229. Kodach L.L., Wiercinska E., de Miranda N.F.C.C., et al. The bone morphogenetic protein pathway is inactivated in the majority of sporadic colorectal cancers. Gastroenterology 2008, 134(5):1332-1341.
230. Yokoe T., Ohmachi T., Inoue H., et al. Clinical significance of growth differentiation factor 11 in colorectal cancer. Int J Oncol 2007, 31(5):1097-1101.
231. Zou H., Harrington J.J., Shire A.M., et al. Highly methylated genes in colorectal neoplasia: implications for screening. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 2007, 16(12):2686-2696.
232. Kisiel J.B., Yab T.C., Taylor W.R., et al. Stool DNA testing for the detection of pancreatic cancer: assessment of methylation marker candidates. Cancer 2012, 118(10):2623-2631.
233. Loh K., Chia J.A., Greco S., et al. Bone morphogenic protein 3 inactivation is an early and frequent event in colorectal cancer development. Genes Chromosom Cancer 2008, 47(6):449-460.
234. Slattery M.L., Lundgreen A., Herrick J.S., et al. Genetic variation in bone morphogenetic protein and colon and rectal cancer. Int J Cancer J Int Cancer 2012, 130(3):653-664.
235. Kim R.Y., Robertson E.J., Solloway M.J. Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. Dev Biol 2001, 235(2):449-466.
236. Cai J., Pardali E., Sánchez-Duffhues G., ten Dijke P. BMP signaling in vascular diseases. FEBS Lett 2012, 586(14):1993-2002.
237. Cogan J., Austin E., Hedges L., et al. Role of BMPR2 alternative splicing in heritable pulmonary arterial hypertension penetrance. Circulation 2012, 126(15):1907-1916.
238. Liu D., Wu W.-H., Mao Y.-M., et al. BMPR2 mutations influence phenotype more obviously in male patients with pulmonary arterial hypertension. Circ Cardiovasc Genet 2012, 5(5):511-518.
239. Jiang Y., Nohe A., Bragdon B., et al. Trapping of BMP receptors in distinct membrane domains inhibits their function in pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 2011, 301(2):L218-L227.
240. Johnson J.A., Hemnes A.R., Perrien D.S., et al. Cytoskeletal defects in Bmpr2-associated pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol 2012, 302(5):L474-L484.
241. Yu P.B., Beppu H., Kawai N., Li E., Bloch K.D. Bone morphogenetic protein (BMP) type II receptor deletion reveals BMP ligand-specific gain of signaling in pulmonary artery smooth muscle cells. J Biol Chem 2005, 280(26):24443-24450.
242. Dewachter L., Adnot S., Guignabert C., et al. Bone morphogenetic protein signalling in heritable versus idiopathic pulmonary hypertension. Eur Respir J 2009, 34(5):1100-1110.
243. Upton P.D., Davies R.J., Tajsic T., Morrell N.W. Transforming growth factor-β(1) represses bone morphogenetic protein-mediated Smad signaling in pulmonary artery smooth muscle cells via Smad3. Am J Respir Cell Mol Biol 2013, 49(6):1135-1145.
244. Drake K.M., Zygmunt D., Mavrakis L., et al. Altered MicroRNA processing in heritable pulmonary arterial hypertension: an important role for Smad-8. Am J Respir Crit Care Med 2011, 184(12):1400-1408.
245. Harrison R.E., Flanagan J.A., Sankelo M., et al. Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J Med Genet 2003, 40(12):865-871.
246. Abdalla S.A., Gallione C.J., Barst R.J., et al. Primary pulmonary hypertension in families with hereditary haemorrhagic telangiectasia. Eur Respir J 2004, 23(3):373-377.
247. Yang J., Li X., Al-Lamki R.S., et al. Sildenafil potentiates bone morphogenetic protein signaling in pulmonary arterial smooth muscle cells and in experimental pulmonary hypertension. Arterioscler Thromb Vasc Biol 2013, 33(1):34-42.
248. Yang J., Li X., Li Y., et al. Id proteins are critical downstream effectors of BMP signaling in human pulmonary arterial smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 2013, 305(4):L312-L321.
249. Drake K.M., Dunmore B.J., McNelly L.N., Morrell N.W., Aldred M.A. Correction of nonsense BMPR2 and SMAD9 mutations by ataluren in pulmonary arterial hypertension. Am J Respir Cell Mol Biol 2013, 49(3):403-409.
250. Teekakirikul P., Milewicz D.M., Miller D.T., et al. Thoracic aortic disease in two patients with juvenile polyposis syndrome and SMAD4 mutations. Am J Med Genet A 2013, 161A(1):185-191.
251. Ricard N., Bidart M., Mallet C., et al. Functional analysis of the BMP9 response of ALK1 mutants from HHT2 patients: a diagnostic tool for novel ACVRL1 mutations. Blood 2010, 116(9):1604-1612.
252. Choi E.-J., Kim Y.H., Choe S., et al. Enhanced responses to angiogenic cues underlie the pathogenesis of hereditary hemorrhagic telangiectasia 2. PloS One 2013, 8(5):e63138.
253. Mitchell D., Pobre E.G., Mulivor A.W., et al. ALK1-Fc inhibits multiple mediators of angiogenesis and suppresses tumor growth. Mol Cancer Ther 2010, 9(2):379-388.
254. Tabatabaeifar M., Schlingmann K.-P., Litwin M., et al. Functional analysis of BMP4 mutations identified in pediatric CAKUT patients. Pediatr Nephrol Berl Ger 2009, 24(12):2361-2368.
255. Weber S., Taylor J.C., Winyard P., et al. SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol JASN 2008, 19(5):891-903.
256. Schild R., Knüppel T., Konrad M., et al. Double homozygous missense mutations in DACH1 and BMP4 in a patient with bilateral cystic renal dysplasia. Nephrol Dial Transpl Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc 2013, 28(1):227-232.
257. Morgan E.A., Nguyen S.B., Scott V., Stadler H.S. Loss of Bmp7 and Fgf8 signaling in Hoxa13-mutant mice causes hypospadia. Dev Camb Engl 2003, 130(14):3095-3109.
258. Chen T., Li Q., Xu J., et al. Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with hypospadias. Eur J Hum Genet EJHG 2007, 15(1):23-28.
259. He J.L., Liu J.H., Liu F., Tan P., Lin T., Li X.L. Mutation screening of BMP4 and Id2 genes in Chinese patients with congenital ureteropelvic junction obstruction. Eur J Pediatr 2012, 171(3):451-456.
260. Tripathi P., Wang Y., Casey A.M., Chen F. Absence of canonical Smad signaling in ureteral and bladder mesenchyme causes ureteropelvic junction obstruction. J Am Soc Nephrol JASN 2012, 23(4):618-628.
261. Wetzel P., Haag J., Câmpean V., et al. Bone morphogenetic protein-7 expression and activity in the human adult normal kidney is predominantly localized to the distal nephron. Kidney Int 2006, 70(4):717-723.
262. Mitu G., Hirschberg R. Bone morphogenetic protein-7 (BMP7) in chronic kidney disease. Front Biosci J Virtual Libr 2008, 13:4726-4739.
263. Bramlage C.P., Tampe B., Koziolek M., et al. Bone morphogenetic protein (BMP)-7 expression is decreased in human hypertensive nephrosclerosis. BMC Nephrol 2010, 11:31.
264. Bramlage C.P., Müller G.A., Tampe B., et al. The role of bone morphogenetic protein-5 (BMP-5) in human nephrosclerosis. J Nephrol 2011, 24(5):647-655.
265. Graw J. Eye development. Curr Top Dev Biol 2010, 90:343-386.
266. Wyatt A.W., Osborne R.J., Stewart H., Ragge N.K. Bone morphogenetic protein 7 (BMP7) mutations are associated with variable ocular, brain, ear, palate, and skeletal anomalies. Hum Mutat 2010, 31(7):781-787.
267. Takenouchi T., Nishina S., Kosaki R., et al. Concurrent deletion of BMP4 and OTX2 genes, two master genes in ophthalmogenesis. Eur J Med Genet 2013, 56(1):50-53.
268. Bakrania P., Efthymiou M., Klein J.C., et al. Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways. Am J Hum Genet 2008, 82(2):304-319.
269. Hayashi S., Okamoto N., Makita Y., Hata A., Imoto I., Inazawa J. Heterozygous deletion at 14q22.1-q22.3 including the BMP4 gene in a patient with psychomotor retardation, congenital corneal opacity and feet polysyndactyly. Am J Med Genet A 2008, 146A(22):2905-2910.
270. Reis L.M., Tyler R.C., Schilter K.F., et al. BMP4 loss-of-function mutations in developmental eye disorders including SHORT syndrome. Hum Genet 2011, 130(4):495-504.
271. Huang H., Song T.-J., Li X., et al. BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci U S A 2009, 106(31):12670-12675.
272. Elsen M., Raschke S., Tennagels N., et al. BMP4 and BMP7 induce the white-to-brown transition of primary human adipose stem cells. Am J Physiol Cell Physiol 2014, 306(5):C431-C440.
273. Böttcher Y., Unbehauen H., Klöting N., et al. Adipose tissue expression and genetic variants of the bone morphogenetic protein receptor 1A gene (BMPR1A) are associated with human obesity. Diabetes 2009, 58(9):2119-2128.
274. Schleinitz D., Klöting N., Böttcher Y., et al. Genetic and evolutionary analyses of the human bone morphogenetic protein receptor 2 (BMPR2) in the pathophysiology of obesity. PloS One 2011, 6(2):e16155.
275. Townsend K.L., Suzuki R., Huang T.L., et al. Bone morphogenetic protein 7 (BMP7) reverses obesity and regulates appetite through a central mTOR pathway. FASEB J Off Publ Fed Am Soc Exp Biol 2012, 26(5):2187-2196.