BMP9 signaling in stem cell differentiation and osteogenesis

American Journal of Stem Cells

Volumn 2, Issue 1, 2013, Pages 1-21

  Lamplot, Joseph D ^a   Qin, Jiaqiang ^a,b   Nan, Guoxin ^a,b   Wang, Jinhua ^a,c   Liu, Xing ^a,b   Yin, Liangjun ^a,c   Tomal, Justin ^a   Li, Ruidong ^a,c   Shui, Wei ^a,c   Zhang, Hongyu ^a,c   Kim, Stephanie H ^a   Zhang, Wenwen ^a,c   Zhang, Jiye ^a,c   Kong, Yuhan ^a,c   Denduluri, Sahitya ^a   Rogers, Mary Rose ^a   Pratt, Abdullah ^a   Haydon, Rex C ^a   Luu, Hue H ^a   Angeles, Jovito ^a   Shi, Lewis L ^a   He, Tong Chuan ^a,b,c   more..

^a UNIVERSITY OF CHICAGO MEDICAL CENTER   (United States)

^b CHILDREN S HOSPITAL OF CHONGQING MEDICAL UNIVERSITY   (China)

^c CHONGQING MEDICAL UNIVERSITY   (China)

Author keywords

BMP; BMP9; Bone regeneration; Igf; Mesenchymal stem cells; Osteogenesis; Signal transduction; TGF ; Wnt

Indexed keywords

2 (2 AMINO 3 METHOXYPHENYL)CHROMONE; 4 (4 FLUOROPHENYL) 2 (4 METHYLSULFINYLPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; ACTIVIN RECEPTOR LIKE KINASE 1; ALKALINE PHOSPHATASE; BETA CATENIN; BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN 2; BONE MORPHOGENETIC PROTEIN 9; CONNECTIVE TISSUE GROWTH FACTOR; ENDOGLIN; GROWTH HORMONE; HELIX LOOP HELIX PROTEIN; HYPOXIA INDUCIBLE FACTOR 1ALPHA; MITOGEN ACTIVATED PROTEIN KINASE; NOTCH RECEPTOR; OSTEOCALCIN; OSTEOGENIC PROTEIN 1; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; RETINOIC ACID; SMAD PROTEIN; SOMATOMEDIN; TRANSCRIPTION FACTOR HES 1; TRANSCRIPTION FACTOR RUNX2; TRANSFORMING GROWTH FACTOR BETA RECEPTOR; TRANSFORMING GROWTH FACTOR BETA1;

ADIPOCYTE; ANGIOGENESIS; BONE DEVELOPMENT; BONE REGENERATION; CARTILAGE CELL; CELL DIFFERENTIATION; GENE ACTIVATION; GENE DELIVERY SYSTEM; HETEROTOPIC OSSIFICATION; HUMAN; IMMUNOHISTOCHEMISTRY; MESENCHYMAL STEM CELL; MUSCLE DEVELOPMENT; NONHUMAN; REVIEW; SIGNAL TRANSDUCTION; SPINE FUSION; WNT SIGNALING PATHWAY;

EID: 84888176716     PISSN: None     EISSN: 21604150     Source Type: Journal    
DOI: None     Document Type: Review

References (186)

1. Kang Q, Sun MH, Cheng H, Peng Y, Montag AG, Deyrup AT, Jiang W, Luu HH, Luo J, Szatkowski JP, Vanichakarn P, Park JY, Li Y, Haydon RC and He TC. Characterization of the distinct orthotopic bone-forming activity of 14 BMPs using recombinant adenovirus-mediated gene delivery. Gene Ther 2004; 11: 1312-1320.
2. Luther G, Wagner ER, Zhu G, Kang Q, Luo Q, Lamplot J, Bi Y, Luo X, Luo J, Teven C, Shi Q, Kim SH, Gao JL, Huang E, Yang K, Rames R, Liu X, Li M, Hu N, Liu H, Su Y, Chen L, He BC, Zuo GW, Deng ZL, Reid RR, Luu HH, Haydon RC and He TC. BMP-9 induced osteogenic differentiation of mesenchymal stem cells: molecular mechanism and therapeutic potential. Curr Gene Ther 2011; 11: 229-240.
3. Urist MR. Bone: formation by autoinduction. Science (New York, N.Y.) 1965; 150: 893-899.
4. Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM and Wang EA. Novel regulators of bone formation: molecular clones and activities. Science 1988; 242: 1528-1534.
5. Hogan BL. Bone morphogenetic proteins: multifunctional regulators of vertebrate development. Genes Dev 1996; 10: 1580-1594.
6. Zhao GQ. Consequences of knocking out BMP signaling in the mouse. Genesis 2003; 35: 43-56.
7. Song JJ, Celeste AJ, Kong FM, Jirtle RL, Rosen V and Thies RS. Bone morphogenetic protein-9 binds to liver cells and stimulates proliferation. Endocrinology 1995; 136: 4293-4297.
8. Chen C, Grzegorzewski KJ, Barash S, Zhao Q, Schneider H, Wang Q, Singh M, Pukac L, Bell AC, Duan R, Coleman T, Duttaroy A, Cheng S, Hirsch J, Zhang L, Lazard Y, Fischer C, Barber MC, Ma ZD, Zhang YQ, Reavey P, Zhong L, Teng B, Sanyal I, Ruben SM, Blondel O and Birse CE. An integrated functional genomics screening program reveals a role for BMP-9 in glucose homeostasis. Nat Biotechnol 2003; 21: 294-301.
9. Lopez-Coviella I, Berse B, Krauss R, Thies RS and Blusztajn JK. Induction and maintenance of the neuronal cholinergic phenotype in the central nervous system by BMP-9. Science 2000; 289: 313-316.
10. Truksa J, Peng H, Lee P and Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci U S A 2006; 103: 10289-10293.
11. Luo J, Tang M, Huang J, He BC, Gao JL, Chen L, Zuo GW, Zhang W, Luo Q, Shi Q, Zhang BQ, Bi Y, Luo X, Jiang W, Su Y, Shen J, Kim SH, Huang E, Gao Y, Zhou JZ, Yang K, Luu HH, Pan X, Haydon RC, Deng ZL and He TC. TGFbeta/BMP type I receptors ALK1 and ALK2 are essential for BMP9-induced osteogenic signaling in mesenchymal stem cells. J Biol Chem 2010; 285: 29588-29598.
12. Cheng H, Jiang W, Phillips FM, Haydon RC, Peng Y, Zhou L, Luu HH, An N, Breyer B, Vanichakarn P, Szatkowski JP, Park JY and He TC. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 2003; 85-A: 1544-1552.
13. Luo Q, Kang Q, Si W, Jiang W, Park JK, Peng Y, Li X, Luu HH, Luo J, Montag AG, Haydon RC and He TC. Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells. J Biol Chem 2004; 279: 55958-55968.
14. Luu HH, Song WX, Luo X, Manning D, Luo J, Deng ZL, Sharff KA, Montag AG, Haydon RC and He TC. Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells. J Orthop Res 2007; 25: 665-677.
15. Peng Y, Kang Q, Cheng H, Li X, Sun MH, Jiang W, Luu HH, Park JY, Haydon RC and He TC. Transcriptional characterization of bone morphogenetic proteins (BMPs)-mediated osteogenic signaling. J Cell Biochem 2003; 90: 1149-1165.
16. Peng Y, Kang Q, Luo Q, Jiang W, Si W, Liu BA, Luu HH, Park JK, Li X, Luo J, Montag AG, Haydon RC and He TC. Inhibitor of DNA binding/ differentiation helix-loop-helix proteins mediate bone morphogenetic protein-induced osteoblast differentiation of mesenchymal stem cells. J Biol Chem 2004; 279: 32941-32949.
17. Brown MA, Zhao Q, Baker KA, Naik C, Chen C, Pukac L, Singh M, Tsareva T, Parice Y, Mahoney A, Roschke V, Sanyal I and Choe S. Crystal structure of BMP-9 and functional interactions with pro-region and receptors. J Biol Chem 2005; 280: 25111-25118.
18. Canalis E, Economides AN and Gazzerro E. Bone morphogenetic proteins, their antagonists, and the skeleton. Endocr Rev 2003; 24: 218-235.
19. Hill JJ, Qiu Y, Hewick RM and Wolfman NM. Regulation of myostatin in vivo by growth and differentiation factor-associated serum protein-1: a novel protein with protease inhibitor and follistatin domains. Mol Endocrinol 2003; 17: 1144-1154.
20. Li JZ, Li H, Sasaki T, Holman D, Beres B, Dumont RJ, Pittman DD, Hankins GR and Helm GA. Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat. Gene Ther 2003; 10: 1735-1743.
21. Sieber C, Kopf J, Hiepen C and Knaus P. Recent advances in BMP receptor signaling. Cytokine Growth Factor Rev 2009; 20: 343-355.
22. Zhang J and Li L. BMP signaling and stem cell regulation. Dev Biol 2005; 284: 1-11.
23. Zhou L, An N, Jiang W, Haydon R, Cheng H, Zhou Q, Breyer B, Feng T and He TC. Fluorescence-based functional assay for Wnt/betacatenin signaling activity. Biotechniques 2002; 33: 1126-1128, 1130, 1132 passim.
24. Alden TD, Pittman DD, Beres EJ, Hankins GR, Kallmes DF, Wisotsky BM, Kerns KM and Helm GA. Percutaneous spinal fusion using bone morphogenetic protein-2 gene therapy. J Neurosurg 1999; 90: 109-114.
25. Alden TD, Pittman DD, Hankins GR, Beres EJ, Engh JA, Das S, Hudson SB, Kerns KM, Kallmes DF and Helm GA. In vivo endochondral bone formation using a bone morphogenetic protein 2 adenoviral vector. Hum Gene Ther 1999; 10: 2245-2253.
26. Baltzer AW, Lattermann C, Whalen JD, Ghivizzani S, Wooley P, Krauspe R, Robbins PD and Evans CH. Potential role of direct adenoviral gene transfer in enhancing fracture repair. Clin Orthop Relat Res 2000; S120-125.
27. Baltzer AW, Lattermann C, Whalen JD, Wooley P, Weiss K, Grimm M, Ghivizzani SC, Robbins PD and Evans CH. Genetic enhancement of fracture repair: healing of an experimental segmental defect by adenoviral transfer of the BMP-2 gene. Gene Ther 2000; 7: 734-739.
28. Bosch P, Musgrave D, Ghivizzani S, Latterman C, Day CS and Huard J. The efficiency of muscle-derived cell-mediated bone formation. Cell Transplant 2000; 9: 463-470.
29. Breitbart AS, Grande DA, Mason JM, Barcia M, James T and Grant RT. Gene-enhanced tissue engineering: applications for bone healing using cultured periosteal cells transduced retrovirally with the BMP-7 gene. Ann Plast Surg 1999; 42: 488-495.
30. Franceschi RT, Wang D, Krebsbach PH and Rutherford RB. Gene therapy for bone formation: in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7. J Cell Biochem 2000; 78: 476-486.
31. Gazit D, Turgeman G, Kelley P, Wang E, Jalenak M, Zilberman Y and Moutsatsos I. Engineered pluripotent mesenchymal cells integrate and differentiate in regenerating bone: a novel cellmediated gene therapy. J Gene Med 1999; 1: 121-133.
32. Krebsbach PH, Gu K, Franceschi RT and Rutherford RB. Gene therapy-directed osteogenesis: BMP-7-transduced human fibroblasts form bone in vivo. Hum Gene Ther 2000; 11: 1201-1210.
33. Lee JY, Musgrave D, Pelinkovic D, Fukushima K, Cummins J, Usas A, Robbins P, Fu FH and Huard J. Effect of bone morphogenetic protein-2-expressing muscle-derived cells on healing of critical-sized bone defects in mice. J Bone Joint Surg Am 2001; 83-A: 1032-1039.
34. Lieberman JR, Le LQ, Wu L, Finerman GA, Berk A, Witte ON and Stevenson S. Regional gene therapy with a BMP-2-producing murine stromal cell line induces heterotopic and orthotopic bone formation in rodents. J Orthop Res 1998; 16: 330-339.
35. Lou J, Xu F, Merkel K and Manske P. Gene therapy: adenovirus-mediated human bone morphogenetic protein-2 gene transfer induces mesenchymal progenitor cell proliferation and differentiation in vitro and bone formation in vivo. J Orthop Res 1999; 17: 43-50.
36. Mason JM, Grande DA, Barcia M, Grant R, Pergolizzi RG and Breitbart AS. Expression of human bone morphogenic protein 7 in primary rabbit periosteal cells: potential utility in gene therapy for osteochondral repair. Gene Ther 1998; 5: 1098-1104.
37. Musgrave DS, Bosch P, Ghivizzani S, Robbins PD, Evans CH and Huard J. Adenovirus-mediated direct gene therapy with bone morphogenetic protein-2 produces bone. Bone 1999; 24: 541-547.
38. Okubo Y, Bessho K, Fujimura K, Iizuka T and Miyatake SI. Osteoinduction by bone morphogenetic protein-2 via adenoviral vector under transient immunosuppression. Biochem Biophys Res Commun 2000; 267: 382-387.
39. Oyama M, Tatlock A, Fukuta S, Kavalkovich K, Nishimura K, Johnstone B, Robbins PD, Evans CH and Niyibizi C. Retrovirally transduced bone marrow stromal cells isolated from a mouse model of human osteogenesis imperfecta (oim) persist in bone and retain the ability to form cartilage and bone after extended passaging. Gene Ther 1999; 6: 321-329.
40. Riew KD, Wright NM, Cheng S, Avioli LV and Lou J. Induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene in a rabbit spinal fusion model. Calcif Tissue Int 1998; 63: 357-360.
41. Ripamonti U, Ramoshebi LN, Matsaba T, Tasker J, Crooks J and Teare J. Bone induction by BMPs/OPs and related family members in primates. J Bone Joint Surg Am 2001; 83-A Suppl 1: S116-127.
42. Sandhu HS, Khan SN, Suh DY and Boden SD. Demineralized bone matrix, bone morphogenetic proteins, and animal models of spine fusion: an overview. Eur Spine J 2001; 10 Suppl 2: S122-131.
43. Varady P, Li JZ, Cunningham M, Beres EJ, Das S, Engh J, Alden TD, Pittman DD, Kerns KM, Kallmes DF and Helm GA. Morphologic analysis of BMP-9 gene therapy-induced osteogenesis. Hum Gene Ther 2001; 12: 697-710.
44. Whang K, Tsai DC, Nam EK, Aitken M, Sprague SM, Patel PK and Healy KE. Ectopic bone formation via rhBMP-2 delivery from porous bioabsorbable polymer scaffolds. J Biomed Mater Res 1998; 42: 491-499.
45. Bostrom MP and Camacho NP. Potential role of bone morphogenetic proteins in fracture healing. Clin Orthop Relat Res 1998; S274-282.
46. Cheng SL, Lou J, Wright NM, Lai CF, Avioli LV and Riew KD. In vitro and in vivo induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene. Calcif Tissue Int 2001; 68: 87-94.
47. Gerhart TN, Kirker-Head CA, Kriz MJ, Holtrop ME, Hennig GE, Hipp J, Schelling SH and Wang E. Healing segmental femoral defects in sheep using recombinant human bone morphogenetic protein. Clin Orthop Relat Res 1993; 317-326.
48. Heckman JD, Boyan BD, Aufdemorte TB and Abbott JT. The use of bone morphogenetic protein in the treatment of non-union in a canine model. J Bone Joint Surg Am 1991; 73: 750-764.
49. Helm GA, Alden TD, Beres EJ, Hudson SB, Das S, Engh JA, Pittman DD, Kerns KM and Kallmes DF. Use of bone morphogenetic protein-9 gene therapy to induce spinal arthrodesis in the rodent. J Neurosurg 2000; 92: 191-196.
50. Lee AR, Wilkins AC, Leather C and Brenton AG. Translational energy spectra for single-electron capture by O2+ in He, Ne, and Ar. Phys Rev A 1994; 50: 1149-1154.
51. Partridge K, Yang X, Clarke NM, Okubo Y, Bessho K, Sebald W, Howdle SM, Shakesheff KM and Oreffo RO. Adenoviral BMP-2 gene transfer in mesenchymal stem cells: in vitro and in vivo bone formation on biodegradable polymer scaffolds. Biochem Biophys Res Commun 2002; 292: 144-152.
52. Varady P, Li JZ, Alden TD, Kallmes DF, Williams MB and Helm GA. CT and radionuclide study of BMP-2 gene therapy-induced bone formation. Acad Radiol 2002; 9: 632-637.
53. Attisano L and Wrana JL. Signal transduction by the TGF-beta superfamily. Science 2002; 296: 1646-1647.
54. Deng ZL, Sharff KA, Tang N, Song WX, Luo J, Luo X, Chen J, Bennett E, Reid R, Manning D, Xue A, Montag AG, Luu HH, Haydon RC and He TC. Regulation of osteogenic differentiation during skeletal development. Front Biosci 2008; 13: 2001-2021.
55. Ducy P and Karsenty G. The family of bone morphogenetic proteins. Kidney Int 2000; 57: 2207-2214.
56. Kang Q, Song WX, Luo Q, Tang N, Luo J, Luo X, Chen J, Bi Y, He BC, Park JK, Jiang W, Tang Y, Huang J, Su Y, Zhu GH, He Y, Yin H, Hu Z, Wang Y, Chen L, Zuo GW, Pan X, Shen J, Vokes T, Reid RR, Haydon RC, Luu HH and He TC. A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells. Stem Cells Dev 2009; 18: 545-559.
57. Luo J, Sun MH, Kang Q, Peng Y, Jiang W, Luu HH, Luo Q, Park JY, Li Y, Haydon RC and He TC. Gene therapy for bone regeneration. Curr Gene Ther 2005; 5: 167-179.
58. Reddi AH. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nat Biotechnol 1998; 16: 247-252.
59. Shi Y and Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 2003; 113: 685-700.
60. Tang N, Song WX, Luo J, Haydon RC and He TC. Osteosarcoma development and stem cell differentiation. Clin Orthop Relat Res 2008; 466: 2114-2130.
61. Wagner ER, He BC, Chen L, Zuo GW, Zhang W, Shi Q, Luo Q, Luo X, Liu B, Luo J, Rastegar F, He CJ, Hu Y, Boody B, Luu HH, He TC, Deng ZL and Haydon RC. Therapeutic Implications of PPAR-gamma in Human Osteosarcoma. PPAR Res 2010; 2010: 956427.
62. He TC. Distinct osteogenic activity of BMPs and their orthopaedic applications. J Musculoskelet Neuronal Interact 2005; 5: 363-366.
63. Lian JB, Stein GS, Javed A, van Wijnen AJ, Stein JL, Montecino M, Hassan MQ, Gaur T, Lengner CJ and Young DW. Networks and hubs for the transcriptional control of osteoblastogenesis. Rev Endocr Metab Disord 2006; 7: 1-16.
64. Yamaguchi A, Komori T and Suda T. Regulation of osteoblast differentiation mediated by bone morphogenetic proteins, hedgehogs, and Cbfa1. Endocr Rev 2000; 21: 393-411.
65. Aubin JE. Regulation of osteoblast formation and function. Rev Endocr Metab Disord 2001; 2: 81-94.
66. He BC, Chen L, Zuo GW, Zhang W, Bi Y, Huang J, Wang Y, Jiang W, Luo Q, Shi Q, Zhang BQ, Liu B, Lei X, Luo J, Luo X, Wagner ER, Kim SH, He CJ, Hu Y, Shen J, Zhou Q, Rastegar F, Deng ZL, Luu HH, He TC and Haydon RC. Synergistic antitumor effect of the activated PPARgamma and retinoid receptors on human osteosarcoma. Clin Cancer Res 2010; 16: 2235-2245.
67. Xu DJ, Zhao YZ, Wang J, He JW, Weng YG, Luo JY. Smads, p38 and ERK1/2 are involved in BMP9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells. BMB Rep 2012; 45: 247-52.
68. Wu N, Zhao Y, Yin Y, Zhang Y and Luo J. Identification and analysis of type II TGF-{beta} receptors in BMP-9-induced osteogenic differentiation of C3H10T1/2 mesenchymal stem cells. Acta Biochim Biophys Sin (Shanghai) 2010; 42: 699-708.
69. Aslan H, Zilberman Y, Arbeli V, Sheyn D, Matan Y, Liebergall M, Li JZ, Helm GA, Gazit D and Gazit Z. Nucleofection-based ex vivo nonviral gene delivery to human stem cells as a platform for tissue regeneration. Tissue Eng 2006; 12: 877-889.
70. Santos JL, Pandita D, Rodrigues J, Pego AP, Granja PL and Tomas H. Non-viral gene delivery to mesenchymal stem cells: methods, strategies and application in bone tissue engineering and regeneration. Curr Gene Ther 2011; 11: 46-57.
71. Sheyn D, Kimelman-Bleich N, Pelled G, Zilberman Y, Gazit D and Gazit Z. Ultrasound-based nonviral gene delivery induces bone formation in vivo. Gene Ther 2008; 15: 257-266.
72. Bergeron E, Senta H, Mailloux A, Park H, Lord E and Faucheux N. Murine preosteoblast differentiation induced by a peptide derived from bone morphogenetic proteins-9. Tissue Eng Part A 2009; 15: 3341-3349.
73. Bergeron E, Leblanc E, Drevelle O, Giguere R, Beauvais S, Grenier G and Faucheux N. The evaluation of ectopic bone formation induced by delivery systems for bone morphogenetic protein-9 or its derived peptide. Tissue Eng Part A 2012; 18: 342-352.
74. Lee JY, Peng H, Usas A, Musgrave D, Cummins J, Pelinkovic D, Jankowski R, Ziran B, Robbins P and Huard J. Enhancement of bone healing based on ex vivo gene therapy using human muscle-derived cells expressing bone morphogenetic protein 2. Hum Gene Ther 2002; 13: 1201-1211.
75. Li JZ, Hankins GR, Kao C, Li H, Kammauff J and Helm GA. Osteogenesis in rats induced by a novel recombinant helper-dependent bone morphogenetic protein-9 (BMP-9) adenovirus. J Gene Med 2003; 5: 748-756.
76. Dumont RJ, Dayoub H, Li JZ, Dumont AS, Kallmes DF, Hankins GR and Helm GA. Ex vivo bone morphogenetic protein-9 gene therapy using human mesenchymal stem cells induces spinal fusion in rodents. Neurosurgery 2002; 51: 1239-1244; discussion 1244-1235.
77. Kimelman-Bleich N, Pelled G, Zilberman Y, Kallai I, Mizrahi O, Tawackoli W, Gazit Z and Gazit D. Targeted gene-and-host progenitor cell therapy for nonunion bone fracture repair. Mol Ther 2011; 19: 53-59.
78. Li X, Chen L, Ke ZY, Yin LJ, Deng ZL. BMP9-Induced Osteogenic Differentiation and Bone Formation of Muscle-Derived Stem Cells. Journal of Biomedicine and Biotechnology 2012; 2012: 7.
79. Leblanc E, Trensz F, Haroun S, Drouin G, Bergeron E, Penton CM, Montanaro F, Roux S, Faucheux N and Grenier G. BMP9-Induced muscle heterotopic ossification requires changes to the skeletal muscle microenvironment. J Bone Miner Res 2010. [Epub ahead of print].
80. Suttapreyasri S, Koontongkaew S, Phongdara A and Leggat U. Expression of bone morphogenetic proteins in normal human intramembranous and endochondral bones. Int J Oral Maxillofac Surg 2006; 35: 444-452.
81. Massague J. TGF-beta signal transduction. Annu Rev Biochem 1998; 67: 753-791.
82. Yamashita H, Ten Dijke P, Heldin CH and Miyazono K. Bone morphogenetic protein receptors. Bone 1996; 19: 569-574.
83. Heldin CH, Miyazono K and ten Dijke P. TGF-beta signalling from cell membrane to nucleus through SMAD proteins. Nature 1997; 390: 465-471.
84. Wrana JL. Regulation of Smad activity. Cell 2000; 100: 189-192.
85. Yamashita H and Miyazono K.[Bone morphogenetic protein (BMP) receptors and signal transduction]. Nippon Rinsho 1999; 57: 220-226.
86. Scharpfenecker M, van Dinther M, Liu Z, van Bezooijen RL, Zhao Q, Pukac L, Lowik CW and ten Dijke P. BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis. J Cell Sci 2007; 120: 964-972.
87. Shao ES, Lin L, Yao Y and Bostrom KI. Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells. Blood 2009; 114: 2197-2206.
88. Upton PD, Davies RJ, Trembath RC and Morrell NW. Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells. J Biol Chem 2009; 284: 15794-15804.
89. Zhao Y, Song T, Wang W, Wang J, He J, Wu N, Tang M, He B and Luo J. P38 and ERK1/2 MAPKs Act in Opposition to Regulate BMP9-Induced Osteogenic Differentiation of Mesenchymal Progenitor Cells. PLoS One 2012; 7: e43383.
90. Kreider BL, Benezra R, Rovera G and Kadesch T. Inhibition of myeloid differentiation by the helix-loop-helix protein Id. Science 1992; 255: 1700-1702.
91. Norton JD. ID helix-loop-helix proteins in cell growth, differentiation and tumorigenesis. J Cell Sci 2000; 113: 3897-3905.
92. Ruzinova MB and Benezra R. Id proteins in development, cell cycle and cancer. Trends Cell Biol 2003; 13: 410-418.
93. Blom IE, Goldschmeding R and Leask A. Gene regulation of connective tissue growth factor: new targets for antifibrotic therapy? Matrix Biol 2002; 21: 473-482.
94. Brigstock DR. The CCN family: a new stimulus package. J Endocrinol 2003; 178: 169-175.
95. Brigstock DR, Goldschmeding R, Katsube KI, Lam SC, Lau LF, Lyons K, Naus C, Perbal B, Riser B, Takigawa M and Yeger H. Proposal for a unified CCN nomenclature. Mol Pathol 2003; 56: 127-128.
96. Lau LF and Lam SC. The CCN family of angiogenic regulators: the integrin connection. Exp Cell Res 1999; 248: 44-57.
97. Moussad EE and Brigstock DR. Connective tissue growth factor: what's in a name? Mol Genet Metab 2000; 71: 276-292.
98. Planque N and Perbal B. A structural approach to the role of CCN (CYR61/CTGF/NOV) proteins in tumourigenesis. Cancer Cell Int 2003; 3: 15.
99. Ivkovic S, Yoon BS, Popoff SN, Safadi FF, Libuda DE, Stephenson RC, Daluiski A and Lyons KM. Connective tissue growth factor coordinates chondrogenesis and angiogenesis during skeletal development. Development 2003; 130: 2779-2791.
100. Ihn H. Pathogenesis of fibrosis: role of TGF-beta and CTGF. Curr Opin Rheumatol 2002; 14: 681-685.
101. Kennedy L, Liu S, Shi-Wen X, Chen Y, Eastwood M, Sabetkar M, Carter DE, Lyons KM, Black CM, Abraham DJ and Leask A. CCN2 is necessary for the function of mouse embryonic fibroblasts. Exp Cell Res 2007; 313: 952-964.
102. Zuo GW, Kohls CD, He BC, Chen L, Zhang W, Shi Q, Zhang BQ, Kang Q, Luo J, Luo X, Wagner ER, Kim SH, Restegar F, Haydon RC, Deng ZL, Luu HH, He TC and Luo Q. The CCN proteins: important signaling mediators in stem cell differentiation and tumorigenesis. Histol Histopathol 2010; 25: 795-806.
103. Sharff KA, Song WX, Luo X, Tang N, Luo J, Chen J, Bi Y, He BC, Huang J, Li X, Jiang W, Zhu GH, Su Y, He Y, Shen J, Wang Y, Chen L, Zuo GW, Liu B, Pan X, Reid RR, Luu HH, Haydon RC and He TC. Hey1 basic helix-loop-helix protein plays an important role in mediating BMP9-induced osteogenic differentiation of mesenchymal progenitor cells. J Biol Chem 2009; 284: 649-659.
104. Massague J and Chen YG. Controlling TGF-beta signaling. Genes Dev 2000; 14: 627-644.
105. Massague J and Wotton D. Transcriptional control by the TGF-beta/Smad signaling system. Embo J 2000; 19: 1745-1754.
106. Siegel PM and Massague J. Cytostatic and apoptotic actions of TGF-beta in homeostasis and cancer. Nat Rev Cancer 2003; 3: 807-821.
107. Siegel PM, Shu W, Cardiff RD, Muller WJ and Massague J. Transforming growth factor beta signaling impairs Neu-induced mammary tumorigenesis while promoting pulmonary metastasis. Proc Natl Acad Sci U S A 2003; 100: 8430-8435.
108. Chen YJ, Wurtz T, Wang CJ, Kuo YR, Yang KD, Huang HC and Wang FS. Recruitment of mesenchymal stem cells and expression of TGF-beta 1 and VEGF in the early stage of shock wave-promoted bone regeneration of segmental defect in rats. J Orthop Res 2004; 22: 526-534.
109. Janssens K, ten Dijke P, Janssens S and Van Hul W. Transforming growth factor-beta1 to the bone. Endocr Rev 2005; 26: 743-774.
110. Li RD, Deng ZL, Hu N, Liang X, Liu B, Luo J, Chen L, Yin L, Luo X, Shui W, He TC and Huang W. Biphasic effects of TGFbeta1 on BMP9-induced osteogenic differentiation of mesenchymal stem cells. BMB Rep 45: 509-514.
111. Kassem M, Kveiborg M and Eriksen EF. Production and action of transforming growth fac-tor-beta in human osteoblast cultures: dependence on cell differentiation and modulation by calcitriol. Eur J Clin Invest 2000; 30: 429-437.
112. Yamada T, Kamiya N, Harada D and Takagi M. Effects of transforming growth factor-beta1 on the gene expression of decorin, biglycan, and alkaline phosphatase in osteoblast precursor cells and more differentiated osteoblast cells. Histochem J 1999; 31: 687-694.
113. Knippenberg M, Helder MN, Doulabi BZ, Bank RA, Wuisman PI and Klein-Nulend J. Differential effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on gene expression of collagen-modifying enzymes in human adipose tissue-derived mesenchymal stem cells. Tissue Eng Part A 2009; 15: 2213-2225.
114. Alliston T, Choy L, Ducy P, Karsenty G and Derynck R. TGF-beta-induced repression of CBFA1 by Smad3 decreases cbfa1 and osteocalcin expression and inhibits osteoblast differentiation. Embo J 2001; 20: 2254-2272.
115. Maeda S, Hayashi M, Komiya S, Imamura T and Miyazono K. Endogenous TGF-beta signaling suppresses maturation of osteoblastic mesenchymal cells. Embo J 2004; 23: 552-563.
116. Derynck R, Zhang Y and Feng XH. Smads: transcriptional activators of TGF-beta responses. Cell 1998; 95: 737-740.
117. Hocevar BA, Brown TL and Howe PH. TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway. Embo J 1999; 18: 1345-1356.
118. Yu K, Bayona W, Kallen CB, Harding HP, Ravera CP, McMahon G, Brown M and Lazar MA. Differential activation of peroxisome proliferatoractivated receptors by eicosanoids. J Biol Chem 1995; 270: 23975-23983.
119. Bergwitz C, Wendlandt T, Kispert A and Brabant G. Wnts differentially regulate colony growth and differentiation of chondrogenic rat calvaria cells. Biochim Biophys Acta 2001; 1538: 129-140.
120. Cadigan KM and Nusse R. Wnt signaling: a common theme in animal development. Genes Dev 1997; 11: 3286-3305.
121. Fischer L, Boland G and Tuan RS. Wnt signaling during BMP-2 stimulation of mesenchymal chondrogenesis. J Cell Biochem 2002; 84: 816-831.
122. Glass DA 2nd and Karsenty G. Molecular bases of the regulation of bone remodeling by the canonical Wnt signaling pathway. Curr Top Dev Biol 2006; 73: 43-84.
123. Glass DA 2nd and Karsenty G. In vivo analysis of Wnt signaling in bone. Endocrinology 2007; 148: 2630-2634.
124. Karsenty G and Wagner EF. Reaching a genetic and molecular understanding of skeletal development. Dev Cell 2002; 2: 389-406.
125. Wang J and Wynshaw-Boris A. The canonical Wnt pathway in early mammalian embryogenesis and stem cell maintenance/differentiation. Curr Opin Genet Dev 2004; 14: 533-539.
126. Tang N, Song WX, Luo J, Luo X, Chen J, Sharff KA, Bi Y, He BC, Huang JY, Zhu GH, Su YX, Jiang W, Tang M, He Y, Wang Y, Chen L, Zuo GW, Shen J, Pan X, Reid RR, Luu HH, Haydon RC and He TC. BMP-9-induced osteogenic differentiation of mesenchymal progenitors requires functional canonical Wnt/beta-catenin signalling. J Cell Mol Med 2009; 13: 2448-2464.
127. Gong Y, Slee RB, Fukai N, Rawadi G, RomanRoman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR and Warman ML. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 2001; 107: 513-523.
128. Huang E, Zhu G, Jiang W, Yang K, Gao Y, Luo Q, Gao JL, Kim SH, Liu X, Li M, Shi Q, Hu N, Wang L, Liu H, Cui J, Zhang W, Li R, Chen X, Kong YH, Zhang J, Wang J, Shen J, Bi Y, Statz J, He BC, Luo J, Wang H, Xiong F, Luu HH, Haydon RC, Yang L and He TC. Growth hormone synergizes with BMP9 in osteogenic differentiation by activating the JAK/STAT/IGF1 pathway in murine multilineage cells. J Bone Miner Res 2012; 27: 1566-1575.
129. Blair JC and Savage MO. The GH-IGF-I axis in children with idiopathic short stature. Trends Endocrinol Metab 2002; 13: 325-330.
130. Brooks AJ and Waters MJ. The growth hormone receptor: mechanism of activation and clinical implications. Nat Rev Endocrinol 2010; 6: 515-525. 19
131. Hull KL and Harvey S. Growth hormone: roles in male reproduction. Endocrine 2000; 13: 243-250.
132. Hull KL and Harvey S. Growth hormone: a reproductive endocrine-paracrine regulator? Rev Reprod 2000; 5: 175-182.
133. Park P and Cohen P. Insulin-like growth factor I (IGF-I) measurements in growth hormone (GH) therapy of idiopathic short stature (ISS). Growth Horm IGF Res 2005; 15 Suppl A: S13-20.
134. Tanaka H. Growth hormone and bone diseases. Endocr J 1998; 45 Suppl: S47-52.
135. Thomas MJ. The molecular basis of growth hormone action. Growth Horm IGF Res 1998; 8: 3-11.
136. Aubin JE. Advances in the osteoblast lineage. Biochem Cell Biol 1998; 76: 899-910.
137. Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S and Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science 1999; 284: 143-147.
138. Prockop DJ. Marrow stromal cells as stem cells for nonhematopoietic tissues. Science 1997; 276: 71-74.
139. Celil AB and Campbell PG. BMP-2 and insulinlike growth factor-I mediate Osterix (Osx) expression in human mesenchymal stem cells via the MAPK and protein kinase D signaling pathways. J Biol Chem 2005; 280: 31353-31359.
140. Chang SF, Chang TK, Peng HH, Yeh YT, Lee DY, Yeh CR, Zhou J, Cheng CK, Chang CA and Chiu JJ. BMP-4 induction of arrest and differentiation of osteoblast-like cells via p21 CIP1 and p27 KIP1 regulation. Mol Endocrinol 2009; 23: 1827-1838.
141. Gallea S, Lallemand F, Atfi A, Rawadi G, Ramez V, Spinella-Jaegle S, Kawai S, Faucheu C, Huet L, Baron R and Roman-Roman S. Activation of mitogen-activated protein kinase cascades is involved in regulation of bone morphogenetic protein-2-induced osteoblast differentiation in pluripotent C2C12 cells. Bone 2001; 28: 491-498.
142. Noth U, Tuli R, Seghatoleslami R, Howard M, Shah A, Hall DJ, Hickok NJ and Tuan RS. Activation of p38 and Smads mediates BMP-2 effects on human trabecular bone-derived osteoblasts. Exp Cell Res 2003; 291: 201-211.
143. Cargnello M and Roux PP. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 2011; 75: 50-83.
144. Miyazono K, Kamiya Y and Morikawa M. Bone morphogenetic protein receptors and signal transduction. J Biochem 2010; 147: 35-51.
145. Verheyen EM. Opposing effects of Wnt and MAPK on BMP/Smad signal duration. Dev Cell 2007; 13: 755-756.
146. Heffron DS and Mandell JW. Opposing roles of ERK and p38 MAP kinases in FGF2-induced astroglial process extension. Mol Cell Neurosci 2005; 28: 779-790.
147. Payne KA, Meszaros LB, Phillippi JA and Huard J. Effect of phosphatidyl inositol 3-kinase, extracellular signal-regulated kinases 1/2, and p38 mitogen-activated protein kinase inhibition on osteogenic differentiation of musclederived stem cells. Tissue Eng Part A 2010; 16: 3647-3655.
148. Shields JM, Mehta H, Pruitt K and Der CJ. Opposing roles of the extracellular signal-regulated kinase and p38 mitogen-activated protein kinase cascades in Ras-mediated downregulation of tropomyosin. Mol Cell Biol 2002; 22: 2304-2317.
149. Majmundar AJ, Wong WJ and Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol Cell 2010; 40: 294-309.
150. Wan C, Shao J, Gilbert SR, Riddle RC, Long F, Johnson RS, Schipani E and Clemens TL. Role of HIF-1alpha in skeletal development. Ann N Y Acad Sci 2010; 1192: 322-326.
151. Hu N, Jiang D, Huang E, Liu X, Li R, Liang X, Kim SH, Chen X, Gao JL, Zhang H, Zhang W, Kong YH, Zhang J, Wang J, Shui W, Luo X, Liu B, Cui J, Rogers MR, Shen J, Zhao C, Wang N, Wu N, Luu HH, Haydon RC, He TC, Huang W. BMP9-regulated angiogenic signaling plays an important role in the osteogenic differentiation of mesenchymal progenitor cells. J Cell Sci 2012.[Epub ahead of print].
152. Wang Y, Wan C, Deng L, Liu X, Cao X, Gilbert SR, Bouxsein ML, Faugere MC, Guldberg RE, Gerstenfeld LC, Haase VH, Johnson RS, Schipani E and Clemens TL. The hypoxia-inducible factor alpha pathway couples angiogenesis to osteogenesis during skeletal development. J Clin Invest 2007; 117: 1616-1626.
153. Tezuka K, Yasuda M, Watanabe N, Morimura N, Kuroda K, Miyatani S and Hozumi N. Stimulation of osteoblastic cell differentiation by Notch. J Bone Miner Res 2002; 17: 231-239.
154. Nobta M, Tsukazaki T, Shibata Y, Xin C, Moriishi T, Sakano S, Shindo H and Yamaguchi A. Critical regulation of bone morphogenetic protein-induced osteoblastic differentiation by Delta1/Jagged1-activated Notch1 signaling. J Biol Chem 2005; 280: 15842-15848.
155. de Jong DS, Steegenga WT, Hendriks JM, van Zoelen EJ, Olijve W and Dechering KJ. Regulation of Notch signaling genes during BMP2-induced differentiation of osteoblast precursor cells. Biochem Biophys Res Commun 2004; 320: 100-107.
156. Giaginis C, Tsantili-Kakoulidou A and Theocharis S. Peroxisome proliferator-activated receptors (PPARs) in the control of bone metabolism. Fundam Clin Pharmacol 2007; 21: 231-244.
157. Muruganandan S, Roman AA and Sinal CJ. Adipocyte differentiation of bone marrow-derived mesenchymal stem cells: cross talk with the osteoblastogenic program. Cell Mol Life Sci 2009; 66: 236-253.
158. Barak Y, Nelson MC, Ong ES, Jones YZ, RuizLozano P, Chien KR, Koder A and Evans RM. PPAR gamma is required for placental, cardiac, and adipose tissue development. Mol Cell 1999; 4: 585-595.
159. Rosen ED, Sarraf P, Troy AE, Bradwin G, Moore K, Milstone DS, Spiegelman BM and Mortensen RM. PPAR gamma is required for the differentiation of adipose tissue in vivo and in vitro. Mol Cell 1999; 4: 611-617.
160. Tontonoz P and Spiegelman BM. Fat and beyond: the diverse biology of PPARgamma. Annu Rev Biochem 2008; 77: 289-312.
161. Chen L, Jiang W, Huang J, He BC, Zuo GW, Zhang W, Luo Q, Shi Q, Zhang BQ, Wagner ER, Luo J, Tang M, Wietholt C, Luo X, Bi Y, Su Y, Liu B, Kim SH, He CJ, Hu Y, Shen J, Rastegar F, Huang E, Gao Y, Gao JL, Zhou JZ, Reid RR, Luu HH, Haydon RC, He TC and Deng ZL. Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation. J Bone Miner Res 2010; 25: 2447-2459.
162. Zhang W, Deng ZL, Chen L, Zuo GW, Luo Q, Shi Q, Zhang BQ, Wagner ER, Rastegar F, Kim SH, Jiang W, Shen J, Huang E, Gao Y, Gao JL, Zhou JZ, Luo J, Huang J, Luo X, Bi Y, Su Y, Yang K, Liu H, Luu HH, Haydon RC, He TC and He BC. Retinoic acids potentiate BMP9-induced osteogenic differentiation of mesenchymal progenitor cells. PLoS One 2010; 5: e11917.
163. Randhawa R and Cohen P. The role of the insulin-like growth factor system in prenatal growth. Mol Genet Metab 2005; 86: 84-90.
164. O'Dell SD and Day IN. Insulin-like growth factor II (IGF-II). Int J Biochem Cell Biol 1998; 30: 767-771.
165. Ducy P, Starbuck M, Priemel M, Shen J, Pinero G, Geoffroy V, Amling M and Karsenty G. A Cbfa1-dependent genetic pathway controls bone formation beyond embryonic development. Genes Dev 1999; 13: 1025-1036.
166. Chawla A, Repa JJ, Evans RM and Mangelsdorf DJ. Nuclear receptors and lipid physiology: opening the X-files. Science 2001; 294: 1866-1870.
167. Mark M, Ghyselinck NB and Chambon P. Function of retinoid nuclear receptors: lessons from genetic and pharmacological dissections of the retinoic acid signaling pathway during mouse embryogenesis. Annu Rev Pharmacol Toxicol 2006; 46: 451-480.
168. Castonguay R, Werner ED, Matthews RG, Presman E, Mulivor AW, Solban N, Sako D, Pearsall RS, Underwood KW, Seehra J, Kumar R and Grinberg AV. Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth. J Biol Chem 2011; 286: 30034-30046.
169. Li B, Yang Y, Jiang S, Ni B, Chen K and Jiang L. Adenovirus-mediated overexpression of BMP-9 inhibits human osteosarcoma cell growth and migration through downregulation of the PI3K/ AKT pathway. Int J Oncol 2012; 41: 1809-1819.
170. Ye L, Kynaston H and Jiang WG. Bone morphogenetic protein-9 induces apoptosis in prostate cancer cells, the role of prostate apoptosis response-4. Mol Cancer Res 2008; 6: 1594-1606.
171. van Meeteren LA, Thorikay M, Bergqvist S, Pardali E, Stampino CG, Hu-Lowe D, Goumans MJ and ten Dijke P. Anti-human activin receptorlike kinase 1 (ALK1) antibody attenuates bone morphogenetic protein 9 (BMP9)-induced ALK1 signaling and interferes with endothelial cell sprouting. J Biol Chem 2012; 287: 18551-18561.
172. Ricard N, Ciais D, Levet S, Subileau M, Mallet C, Zimmers TA, Lee SJ, Bidart M, Feige JJ and Bailly S. BMP9 and BMP10 are critical for postnatal retinal vascular remodeling. Blood 2012; 119: 6162-6171.
173. Suzuki Y, Ohga N, Morishita Y, Hida K, Miyazono K and Watabe T. BMP-9 induces proliferation of multiple types of endothelial cells in vitro and in vivo. J Cell Sci 2010; 123: 1684-1692.
174. David L, Mallet C, Keramidas M, Lamande N, Gasc JM, Dupuis-Girod S, Plauchu H, Feige JJ and Bailly S. Bone morphogenetic protein-9 is a circulating vascular quiescence factor. Circ Res 2008; 102: 914-922.
175. Park JE, Shao D, Upton PD, Desouza P, Adcock IM, Davies RJ, Morrell NW, Griffiths MJ and Wort SJ. BMP-9 induced endothelial cell tubule formation and inhibition of migration involves Smad1 driven endothelin-1 production. PLoS One 2012; 7: e30075.
176. Yao Y, Jumabay M, Ly A, Radparvar M, Wang AH, Abdmaulen R and Bostrom KI. Crossvein-less 2 regulates bone morphogenetic protein 9 in human and mouse vascular endothelium. Blood 2012; 119: 5037-5047.
177. Cunha SI, Pardali E, Thorikay M, Anderberg C, Hawinkels L, Goumans MJ, Seehra J, Heldin CH, ten Dijke P and Pietras K. Genetic and pharmacological targeting of activin receptor-like kinase 1 impairs tumor growth and angiogenesis. J Exp Med 2010; 207: 85-100.
178. Cunha SI and Pietras K. ALK1 as an emerging target for antiangiogenic therapy of cancer. Blood 2011; 117: 6999-7006.
179. Lopez-Coviella I, Follettie MT, Mellott TJ, Kovacheva VP, Slack BE, Diesl V, Berse B, Thies RS and Blusztajn JK. Bone morphogenetic protein 9 induces the transcriptome of basal forebrain cholinergic neurons. Proc Natl Acad Sci U S A 2005; 102: 6984-6989.
180. Lopez-Coviella I, Mellott TJ, Schnitzler AC and Blusztajn JK. BMP9 protects septal neurons from axotomy-evoked loss of cholinergic phenotype. PLoS One 2011; 6: e21166.
181. Schnitzler AC, Lopez-Coviella I and Blusztajn JK. Differential modulation of nerve growth factor receptor (p75) and cholinergic gene expression in purified p75-expressing and nonexpressing basal forebrain neurons by BMP9. Brain Res 2008; 1246: 19-28.
182. Schnitzler AC, Mellott TJ, Lopez-Coviella I, Tallini YN, Kotlikoff MI, Follettie MT and Blusztajn JK. BMP9 (bone morphogenetic protein 9) induces NGF as an autocrine/paracrine cholinergic trophic factor in developing basal forebrain neurons. J Neurosci 2010; 30: 8221-8228.
183. Caperuto LC, Anhe GF, Cambiaghi TD, Akamine EH, do Carmo Buonfiglio D, Cipolla-Neto J, Curi R and Bordin S. Modulation of bone morphogenetic protein-9 expression and processing by insulin, glucose, and glucocorticoids: possible candidate for hepatic insulin-sensitizing substance. Endocrinology 2008; 149: 6326-6335.
184. Sosa I, Cvijanovic O, Celic T, Cuculic D, Crncevic-Orlic Z, Vukelic L, Zoricic Cvek S, Dudaric L, Bosnar A and Bobinac D. Hepatoregenerative role of bone morphogenetic protein-9. Med Sci Monit 2011; 17: HY33-35.
185. Blunk T, Sieminski AL, Appel B, Croft C, Courter DL, Chieh JJ, Goepferich A, Khurana JS and Gooch KJ. Bone morphogenetic protein 9: a potent modulator of cartilage development in vitro. Growth Factors 2003; 21: 71-77.
186. Majumdar MK, Wang E and Morris EA. BMP-2 and BMP-9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL-1. J Cell Physiol 2001; 189: 275-284.