Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Signalling Enhances Osteogenesis in UMR-106 Cell Line

Journal of Molecular Neuroscience

Volumn 54, Issue 3, 2014, Pages 555-573

  Juhász, Tamás ^a   Matta, Csaba ^a   Katona, Éva ^a   Somogyi, Csilla ^a   Takács, Roland ^a   Hajdú, Tibor ^a   Helgadottir, Solveig Lind ^a   Fodor, János ^a   Csernoch, László ^a   Tóth, Gábor ^b   Bakó, Éva ^a   Reglődi, Dóra ^c   Tamás, Andrea ^c   Zákány, Róza ^a  

^a UNIVERSITY OF DEBRECEN   (Hungary)

^b UNIVERSITY OF SZEGED   (Hungary)

^c UNIVERSITY OF PÉCS   (Hungary)

Author keywords

Cellular proliferation; CREB; Mineralisation; PACAP 6 38; PKA; Sonic hedgehog

Indexed keywords

ALKALINE PHOSPHATASE; BONE MORPHOGENETIC PROTEIN; CELL SURFACE RECEPTOR; COLLAGEN TYPE 1; CYCLIC AMP DEPENDENT PROTEIN KINASE; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; GLI PROTEIN, RAT; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE; HYPOPHYSIS ADENYLATE CYCLASE ACTIVATING POLYPEPTIDE RECEPTOR 1; KRUPPEL LIKE FACTOR; OSTERIX PROTEIN, RAT; PATCHED RECEPTORS; SMAD1 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR RUNX2;

AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; BONE DEVELOPMENT; CELL PROLIFERATION; GENETICS; METABOLISM; RAT; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ALKALINE PHOSPHATASE; ANIMALS; BONE MORPHOGENETIC PROTEINS; CELL LINE, TUMOR; CELL PROLIFERATION; COLLAGEN TYPE I; CORE BINDING FACTOR ALPHA 1 SUBUNIT; CYCLIC AMP RESPONSE ELEMENT-BINDING PROTEIN; CYCLIC AMP-DEPENDENT PROTEIN KINASES; KRUPPEL-LIKE TRANSCRIPTION FACTORS; OSTEOGENESIS; PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE; RATS; RECEPTORS, CELL SURFACE; RECEPTORS, PITUITARY ADENYLATE CYCLASE-ACTIVATING POLYPEPTIDE, TYPE I; SIGNAL TRANSDUCTION; SMAD1 PROTEIN; TRANSCRIPTION FACTORS;

EID: 84939883199     PISSN: 08958696     EISSN: 15591166     Source Type: Journal    
DOI: 10.1007/s12031-014-0389-1     Document Type: Article

References (94)

1. Ago Y, Yoneyama M, Ishihama T, Kataoka S, Kawada K, Tanaka T et al (2011) Role of endogenous pituitary adenylate cyclase-activating polypeptide in adult hippocampal neurogenesis. Neuroscience 172:554–561
2. Aoyagi K, Takahashi M (2001) Pituitary adenylate cyclase-activating polypeptide enhances Ca(2+)-dependent neurotransmitter release from PC12 cells and cultured cerebellar granule cells without affecting intracellular Ca(2+) mobilization. Biochem Biophys Res Commun 286:646–651
3. Bae IH, Jeong BC, Kook MS, Kim SH, Koh JT (2013) Evaluation of a thiolated chitosan scaffold for local delivery of BMP-2 for osteogenic differentiation and ectopic bone formation. Biomed Res Int 2013:878930
4. Bastida MF, Sheth R, Ros MA (2009) A BMP-Shh negative-feedback loop restricts Shh expression during limb development. Development 136:3779–3789
5. Bei K, Du Z, Xiong Y, Liao J, Su B, Wu L (2012) BMP7 can promote osteogenic differentiation of human periosteal cells in vitro. Mol Biol Rep 39:8845–8851
6. Bergstrom AL, Hannibal J, Hindersson P, Fahrenkrug J (2003) Light-induced phase shift in the Syrian hamster (Mesocricetus auratus) is attenuated by the PACAP receptor antagonist PACAP6-38 or PACAP immunoneutralization. Eur J Neurosci 18:2552–2562
7. Borzsei R, Mark L, Tamas A, Bagoly T, Bay C, Csanaky K et al (2009) Presence of pituitary adenylate cyclase activating polypeptide-38 in human plasma and milk. Eur J Endocrinol 160:561–565
8. Braas KM, May V, Harakall SA, Hardwick JC, Parsons RL (1998) Pituitary adenylate cyclase-activating polypeptide expression and modulation of neuronal excitability in guinea pig cardiac ganglia. J Neurosci 18:9766–9779
9. Braas KM, Schutz KC, Bond JP, Vizzard MA, Girard BM, May V (2007) Microarray analyses of pituitary adenylate cyclase activating polypeptide (PACAP)-regulated gene targets in sympathetic neurons. Peptides 28:1856–1870
10. Brennan D, Chen X, Cheng L, Mahoney M, Riobo NA (2012) Noncanonical Hedgehog signaling. Vitam Horm 88:55–72
11. Castorina A, Giunta S, Mazzone V, Cardile V, D’Agata V (2010) Effects of PACAP and VIP on hyperglycemia-induced proliferation in murine microvascular endothelial cells. Peptides 31:2276–2283
12. Chen G, Deng C, Li YP (2012) TGF-beta and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 8:272–288
13. Drissi MH, Li X, Sheu TJ, Zuscik MJ, Schwarz EM, Puzas JE, Rosier RN et al (2003) Runx2/Cbfa1 stimulation by retinoic acid is potentiated by BMP2 signaling through interaction with Smad1 on the collagen X promoter in chondrocytes. J Cell Biochem 90:1287–1298
14. Ehlen HW, Buelens LA, Vortkamp A (2006) Hedgehog signaling in skeletal development. Birth Defects Res C Embryo Today 78:267–279
15. Falluel-Morel A, Aubert N, Vaudry D, Desfeux A, Allais A, Burel D et al (2008) Interactions of PACAP and ceramides in the control of granule cell apoptosis during cerebellar development. J Mol Neurosci 36:8–15
16. Forrest SM, Ng KW, Findlay DM, Michelangeli VP, Livesey SA, Partridge NC et al (1985) Characterization of an osteoblast-like clonal cell line which responds to both parathyroid hormone and calcitonin. Calcif Tissue Int 37:51–56
17. Franceschi RT, Xiao G (2003) Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. J Cell Biochem 88:446–454
18. Gonkowski S, Całka J (2012) Changes in pituitary adenylate cyclase-activating Peptide 27-like immunoreactive nervous structures in the porcine descending colon during selected pathological processes. J Mol Neurosci 48(3):777–787
19. Gourlet P, Vandermeers A, Vertongen P, Rathe J, De NP, Cnudde J et al (1997) Development of high affinity selective VIP1 receptor agonists. Peptides 18:1539–1545
20. Han JB, Sang F, Chang JJ, Hua YQ, Shi WD, Tang LH et al (2013) Arsenic trioxide inhibits viability of pancreatic cancer stem cells in culture and in a xenograft model via binding to SHH-Gli. Onco Targets Ther 6:1129–1138
21. Hirotsu M, Setoguchi T, Sasaki H, Matsunoshita Y, Gao H, Nagao H et al (2010) Smoothened as a new therapeutic target for human osteosarcoma. Mol Cancer 12(9):5
22. Hodges RR, Rios JD, Vrouvlianis J, Ota I, Zoukhri D, Dartt DA (2006) Roles of protein kinase C, Ca2+, Pyk2, and c-Src in agonist activation of rat lacrimal gland p42/p44 MAPK. Invest Ophthalmol Vis Sci 47:3352–3359
23. Hojo H, Ohba S, Yano F, Saito T, Ikeda T, Nakajima K et al (2012) Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification. J Biol Chem 287:17860–17869
24. Holighaus Y, Mustafa T, Eiden LE (2011) PAC1hop, null and hip receptors mediate differential signaling through cyclic AMP and calcium leading to splice variant-specific gene induction in neural cells. Peptides 32:1647–1655
25. Horvath G, Brubel R, Kovacs K, Reglodi D, Opper B, Ferencz A et al (2011) Effects of PACAP on oxidative stress-induced cell death in rat kidney and human hepatocyte cells. J Mol Neurosci 43:67–75
26. Hu X, Zhang S, Chen G, Lin C, Huang Z, Chen Y et al (2013) Expression of SHH signaling molecules in the developing human primary dentition. BMC Dev Biol 13:11
27. Huang KP, Huang FL (1991) Purification and analysis of protein kinase C isozymes. Methods Enzymol 200:241–252
28. Inglott MA, Lerner EA, Pilowsky PM, Farnham MM (2012) Activation of PAC(1) and VPAC receptor subtypes elicits differential physiological responses from sympathetic preganglionic neurons in the anaesthetized rat. Br J Pharmacol 167:1089–1098
29. James AW, Leucht P, Levi B, Carre AL, Xu Y, Helms JA et al (2010) Sonic Hedgehog influences the balance of osteogenesis and adipogenesis in mouse adipose-derived stromal cells. Tissue Eng Part A 16:2605–2616
30. Jansen-Olesen I, Baun M, Amrutkar DV, Ramachandran R, Christophersen DV, Olesen J (2014) PACAP-38 but not VIP induces release of CGRP from trigeminal nucleus caudalis via a receptor distinct from the PAC1 receptor. Neuropeptides. doi:10.1016/j.npep.2014.01.004
31. Jiang Q, Du J, Yin X, Shan Z, Ma Y, Ma P et al (2013) Shh signaling, negatively regulated by BMP signaling, inhibits the osteo/dentinogenic differentiation potentials of mesenchymal stem cells from apical papilla. Mol Cell Biochem 383:85–93
32. Jolivel V, Basille M, Aubert N, de Jouffrey S, Ancian P, Le Bigot JF et al (2009) Distribution and functional characterization of pituitary adenylate cyclase-activating polypeptide receptors in the brain of non-human primates. Neuroscience 160:434–451
33. Jonason JH, Xiao G, Zhang M, Xing L, Chen D (2009) Post-translational regulation of Runx2 in bone and cartilage. J Dent Res 88:693–703
34. Jones KB, Mollano AV, Morcuende JA, Cooper RR, Saltzman CL (2004) Bone and brain: a review of neural, hormonal, and musculoskeletal connections. Iowa Orthop J 24:123–132
35. Jozsa R, Hollosy T, Tamas A, Toth G, Lengvari I, Reglodi D (2005) Pituitary adenylate cyclase activating polypeptide plays a role in olfactory memory formation in chicken. Peptides 26:2344–2350
36. Juhász T, Matta C, Katona E, Somogyi C, Takács R, Gergely P et al (2014) Pituitary adenylate cyclase activating polypeptide (PACAP) signalling exerts chondrogenesis promoting and protecting effects: implication of calcineurin as a downstream target. PLoS One 9(3):e91541
37. Kim JH, Liu X, Wang J, Chen X, Zhang H, Kim SH et al (2013) Wnt signaling in bone formation and its therapeutic potential for bone diseases. Ther Adv Musculoskelet Dis 5:13–31
38. Kiuru M, Solomon J, Ghali B, van der Meulen M, Crystal RG, Hidaka C (2009) Transient overexpression of sonic hedgehog alters the architecture and mechanical properties of trabecular bone. J Bone Mineral Res 24:1598–1607
39. Kovacs CS, Chik CL, Li B, Karpinski E, Ho AK (1996) Pituitary adenylate cyclase-activating peptide stimulates cyclic AMP accumulation in UMR 106 osteoblast-like cells. J Endocrinol 149:287–295
40. Lavery K, Swain P, Falb D, Aoui-Ismaili MH (2008) BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. J Biol Chem 283:20948–20958
41. Li YL, Xiao ZS (2007) Advances in Runx2 regulation and its isoforms. Med Hypotheses 68:169–175
42. Lo KW, Kan HM, Ashe KM, Laurencin CT (2012) The small molecule PKA-specific cyclic AMP analogue as an inducer of osteoblast-like cells differentiation and mineralization. J Tissue Eng Regen Med 6:40–48
43. MacDonald JF, Jackson MF, Beazely MA (2007) G protein-coupled receptors control NMDARs and metaplasticity in the hippocampus. Biochim Biophys Acta 1768:941–951
44. Marie PJ (2012) Fibroblast growth factor signaling controlling bone formation: an update. Gene 498:1–4
45. Matsumoto S, Arakawa Y, Ohishi M, Yanaihara H, Iwanaga T, Kurokawa N (2008) Suppressive action of pituitary adenylate cyclase activating polypeptide (PACAP) on proliferation of immature mouse Leydig cell line TM3 cells. Biomed Res 29:321–330
46. Matta C, Fodor J, Szijgyarto Z, Juhasz T, Gergely P, Csernoch L et al (2008) Cytosolic free Ca2+ concentration exhibits a characteristic temporal pattern during in vitro cartilage differentiation: a possible regulatory role of calcineurin in Ca-signalling of chondrogenic cells. Cell Calcium 44:310–323
47. Midura RJ, McQuillan DJ, Benham KJ, Fisher LW, Hascall VC (1990) A rat osteogenic cell line (UMR 106-01) synthesizes a highly sulfated form of bone sialoprotein. J Biol Chem 265:5285–5291
48. Miyata A, Arimura A, Dahl RR, Minamino N, Uehara A, Jiang L et al (1989) Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. Biochem Biophys Res Commun 164:567–574
49. Morita K, Sakakibara A, Kitayama S, Kumagai K, Tanne K, Dohi T (2002) Pituitary adenylate cyclase-activating polypeptide induces a sustained increase in intracellular free Ca(2+) concentration and catechol amine release by activating Ca(2+) influx via receptor-stimulated Ca(2+) entry, independent of store-operated Ca(2+) channels, and voltage-dependent Ca(2+) channels in bovine adrenal medullary chromaffin cells. J Pharmacol Exp Ther 302:972–982
50. Nagata A, Tanaka T, Minezawa A, Poyurovsky M, Mayama T, Suzuki S et al (2009) cAMP activation by PACAP/VIP stimulates IL-6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells. J Cell Physiol 221:75–83
51. Nakamachi T, Nakamura K, Oshida K, Kagami N, Mori H, Watanabe J et al (2011) Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates proliferation of reactive astrocytes in vitro. J Mol Neurosci 43:16–21
52. Niewiadomski P, Zhujiang A, Youssef M, Waschek JA (2013) Interaction of PACAP with Sonic hedgehog reveals complex regulation of the hedgehog pathway by PKA. Cell Signal 25:2222–2230
53. Nishimoto M, Furuta A, Aoki S, Kudo Y, Miyakawa H, Wada K (2007) PACAP/PAC1 autocrine system promotes proliferation and astrogenesis in neural progenitor cells. Glia 55:317–327
54. Ochiai T, Shibukawa Y, Nagayama M, Mundy C, Yasuda T, Okabe T et al (2010) Indian hedgehog roles in post-natal TMJ development and organization. J Dent Res 89:349–354
55. Ohta S, Gregg C, Weiss S (2006) Pituitary adenylate cyclase-activating polypeptide regulates forebrain neural stem cells and neurogenesis in vitro and in vivo. J Neurosci Res 84:1177–1186
56. Ok CY, Singh RR, Vega F (2012) Aberrant activation of the hedgehog signaling pathway in malignant hematological neoplasms. Am J Pathol 180:2–11
57. Osipenko ON, Barrie AP, Allen JM, Gurney AM (2000) Pituitary adenylyl cyclase-activating peptide activates multiple intracellular signaling pathways to regulate ion channels in PC12 cells. J Biol Chem 275:16626–16631
58. Pan A, Chang L, Nguyen A, James AW (2013) A review of hedgehog signaling in cranial bone development. Front Physiol 4:61
59. Payet MD, Bilodeau L, Breault L, Fournier A, Yon L, Vaudry H et al (2003) PAC1 receptor activation by PACAP-38 mediates Ca2+ release from a cAMP-dependent pool in human fetal adrenal gland chromaffin cells. J Biol Chem 278:1663–1670
60. Perrier-Groult E, Pasdeloup M, Malbouyres M, Galera P, Mallein-Gerin F (2013) Control of collagen production in mouse chondrocytes by using a combination of bone morphogenetic protein-2 and small interfering RNA targeting Col1a1 for hydrogel-based tissue-engineered cartilage. Tissue Eng Part C Methods 19:652–664
61. Persson E, Lerner UH (2005) The neuropeptide VIP potentiates IL-6 production induced by proinflammatory osteotropic cytokines in calvarial osteoblasts and the osteoblastic cell line MC3T3-E1. Biochem Biophys Res Commun 335:705–711
62. Persson E, Lerner UH (2011) The neuropeptide VIP regulates the expression of osteoclastogenic factors in osteoblasts. J Cell Biochem 112:3732–3741
63. Pirone A, Baoan D, Piano I, Santina LD, Baglini A, Lenzi C (2011) Pituitary adenylate cyclase-activating peptide (PACAP) immunoreactivity distribution in the small intestine of the adult New Hampshire chicken. Acta Histochem 113:477–483
64. Regard JB, Malhotra D, Gvozdenovic-Jeremic J, Josey M, Chen M, Weinstein LS et al (2013) Activation of Hedgehog signaling by loss of GNAS causes heterotopic ossification. Nat Med 19:1505–1512
65. Reglodi D, Borzsei R, Bagoly T, Boronkai A, Racz B, Tamas A et al (2008) Agonistic behavior of PACAP6-38 on sensory nerve terminals and cytotrophoblast cells. J Mol Neurosci 36:270–278
66. Reglodi D, Gyarmati J, Ertl T, Borzsei R, Bodis J, Tamas A et al (2010) Alterations of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity in the human plasma during pregnancy and after birth. J Endocrinol Investig 33:443–445
67. Reglodi D, Tamas A, Koppan M, Szogyi D, Welke L (2012) Role of PACAP in female fertility and reproduction at gonadal level—recent advances. Front Endocrinol (Lausanne) 11(3):155
68. Sanchez A, Chiriva-Internati M, Grammas P (2008) Transduction of PACAP38 protects primary cortical neurons from neurotoxic injury. Neurosci Lett 448:52–55
69. Seeliger S, Buddenkotte J, Schmidt-Choudhury A, Rosignoli C, Shpacovitch V, von Arnim U et al (2010) Pituitary adenylate cyclase activating polypeptide: an important vascular regulator in human skin in vivo. Am J Pathol 177:2563–2575
70. Shioda S, Legradi G, Leung WC, Nakajo S, Nakaya K, Arimura A (1994) Localization of pituitary adenylate cyclase-activating polypeptide and its messenger ribonucleic acid in the rat testis by light and electron microscopic immunocytochemistry and in situ hybridization. Endocrinology 135:818–825
71. Shioda S, Ohtaki H, Nakamachi T, Dohi K, Watanabe J, Nakajo S et al (2006) Pleiotropic functions of PACAP in the CNS: neuroprotection and neurodevelopment. Ann N Y Acad Sci 1070:550–560
72. Shpakov AO, Derkach KV, Chistiakova OV, Bondareva VM (2011) Functional state of adenylate cyclase signaling system in testis and ovary of fasted rats. Zh Evol Biokhim Fiziol 47:40–48
73. Siddappa R, Martens A, Doorn J, Leusink A, Olivo C, Licht R et al (2008) cAMP/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo. Proc Natl Acad Sci U S A 105:7281–7286
74. St-Jacques B, Hammerschmidt M, McMahon AP (1999) Indian hedgehog signaling regulates proliferation and differentiation of chondrocytes and is essential for bone formation. Genes Dev 13:2072–2086
75. Strange-Vognsen HH, Arnbjerg J, Hannibal J (1997) Immunocytochemical demonstration of pituitary adenylate cyclase activating polypeptide (PACAP) in the porcine epiphyseal cartilage canals. Neuropeptides 31:137–141
76. Tamas A, Reglodi D, Farkas O, Kovesdi E, Pal J, Povlishock JT et al (2012) Effect of PACAP in Central and Peripheral Nerve Injuries. Int J Mol Sci 13:8430–8448
77. Toriyama M, Mizuno N, Fukami T, Iguchi T, Toriyama M, Tago K et al (2012) Phosphorylation of doublecortin by protein kinase A orchestrates microtubule and actin dynamics to promote neuronal progenitor cell migration. J Biol Chem 287:12691–12702
78. Tu X, Joeng KS, Long F (2012) Indian hedgehog requires additional effectors besides Runx2 to induce osteoblast differentiation. Dev Biol 362:76–82
79. Vandermeers A, Vandenborre S, Hou X, De NP, Robberecht P, Vandermeers-Piret MC et al (1992) Antagonistic properties are shifted back to agonistic properties by further N-terminal shortening of pituitary adenylate-cyclase-activating peptides in human neuroblastoma NB-OK-1 cell membranes. Eur J Biochem 208:815–819
80. Vaudry D, Falluel-Morel A, Bourgault S, Basille M, Burel D, Wurtz O et al (2009) Pituitary adenylate cyclase-activating polypeptide and its receptors: 20 years after the discovery. Pharmacol Rev 61:283–357
81. Vazin T, Ashton RS, Conway A, Rode NA, Lee SM, Bravo V et al (2014) The effect of multivalent Sonic hedgehog on differentiation of human embryonic stem cells into dopaminergic and GABAergic neurons. Biomaterials 35(3):941–948
82. Wada Y, Nakamachi T, Endo K, Seki T, Ohtaki H, Tsuchikawa D et al (2013) PACAP attenuates NMDA-induced retinal damage in association with modulation of the microglia/macrophage status into an acquired deactivation subtype. J Mol Neurosci 51(2):493–502
83. Walker CS, Sundrum T, Hay DL (2013) PACAP receptor pharmacology and agonist bias: Analysis in primary neurons and glia from the trigeminal ganglia and transfected cells. Br J Pharmacol 171:1521–1533
84. Wang L, Park P, La MF, Than K, Rahman S, Lin CY (2013) Bone formation induced by BMP-2 in human osteosarcoma cells. Int J Oncol 43:1095–1102
85. Waschek JA, Cicco-Bloom EM, Lelievre V, Zhou X, Hu Z (2000) PACAP action in nervous system development, regeneration, and neuroblastoma cell proliferation. Ann NY Acad Sci 921:129–136
86. Waschek JA, Cicco-Bloom E, Nicot A, Lelievre V (2006) Hedgehog signaling: new targets for GPCRs coupled to cAMP and protein kinase A. Ann NY Acad Sci 1070:120–128
87. Watanabe J, Nakamachi T, Matsuno R, Hayashi D, Nakamura M, Kikuyama S et al (2007) Localization, characterization and function of pituitary adenylate cyclase-activating polypeptide during brain development. Peptides 28:1713–1719
88. Wu X, Hou T, Luo F, Xing J, He Q, Jin H et al (2013) Vascular endothelial growth factor and physiological compressive loading synergistically promote bone formation of tissue-engineered bone. Tissue Eng Part A 19:2486–2494
89. Yan Y, Zhou X, Pan Z, Ma J, Waschek JA, DiCicco-Bloom E (2013) Pro- and anti-mitogenic actions of pituitary adenylate cyclase-activating polypeptide in developing cerebral cortex: potential mediation by developmental switch of PAC1 receptor mRNA isoforms. J Neurosci 33(9):3865–3878
90. Yan XZ, Yang W, Yang F, Kersten-Niessen M, Jansen JA, Both SK (2014) Effects of continuous passaging on mineralization of MC3T3-E1 cells with improved osteogenic culture protocol tissue. Eng Part C Methods 20(3):198–204
91. Yang J, Shi QD, Song TB, Feng GF, Zang WJ, Zong CH et al (2013) Vasoactive intestinal peptide increases VEGF expression to promote proliferation of brain vascular endothelial cells via the cAMP/PKA pathway after ischemic insult in vitro. Peptides 42:105–111
92. Zhang R, Edwards JR, Ko SY, Dong S, Liu H, Oyajobi BO et al (2011) Transcriptional regulation of BMP2 expression by the PTH-CREB signaling pathway in osteoblasts. PLoS One 6:e20780
93. Zhu F, Friedman MS, Luo W, Woolf P, Hankenson KD (2012) The transcription factor osterix (SP7) regulates BMP6-induced human osteoblast differentiation. J Cell Physiol 227:2677–2685
94. Zouani OF, Rami L, Lei Y, Durrieu MC (2013) Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling. Biol Open 2:872–881