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Clinical Oral Investigations

, Volume 18, Issue 8, pp 1925–1939 | Cite as

Gene expression profile of compressed primary human cementoblasts before and after IL-1β stimulation

  • Katja DierckeEmail author
  • Sebastian Zingler
  • Annette Kohl
  • Christopher J. Lux
  • Ralf Erber
Original Article

Abstract

Objectives

Root resorptions due to a reduced repair function of cementoblasts are common side effects during orthodontic tooth movement (OTM). The mechanisms, which lead to an impaired cementoblast function, are not fully understood. Therefore, we aimed to investigate changes in the gene expression of cementoblasts during mechanical stimulus under inflammatory conditions.

Materials and methods

Human primary cementoblasts (HPCB) were exposed to compression for 6 h or stimulation with IL-1β for 96 h and subsequent 6 h compression. Genome-wide expression analysis was performed using microarray analysis. Prominent gene expression alterations (COX2, AXUD1, FOSB, CCL2, IFI6, and PTGES) were verified by quantitative RT-PCR (qRT-PCR) in two HPCB populations. A caspase 3/7 activity assay was used to determine caspase-3 and caspase-7 activity in stressed cells.

Results

Gene expression cluster analysis revealed apoptosis as an important process induced under both conditions. Apoptosis (pro- and anti-apoptotic) related gene expression was most relevant after pro-inflammatory stimulation and compression. qRT-PCR analysis confirmed significant up-regulation of COX2, AXUD1, and FOSB in both HPCB populations after compression, while selected genes significantly increased after pro-inflammatory stimulation and compression. Compression of cementoblasts increased caspase. The combination of pro-inflammatory stimulation and compression led to a slightly smaller increase of caspase activity.

Conclusions

Gene ontology analysis showed that compressed HPCB up-regulate genes that are associated with apoptosis. Combining compression with a pro-inflammatory stimulus (IL-1β) augmented the positive regulation of apoptosis-related pathways. The induction of apoptosis related gene expression (pro- and anti-apoptotic genes) in cementoblasts suggests an involvement of apoptosis in cementoblast regulation during OTM.

Clinical relevance

As apoptosis is induced in HPCB after compression and inflammation, it is conceivable that HPCB cell death might contribute to root resorptions due to a loss of repair activity of cementoblasts. Further studies should be conducted to clarify the implication of the identified genes on root resorptions in order to develop therapeutic strategies to prevent a shortening of roots.

Keywords

Cementoblasts Tooth movement Root resorption Expression analysis Apoptosis Compression Inflammation 

Notes

Acknowledgments

This study received financial support from the Deutschen Gesellschaft für Zahn-, Mund- und Kieferheilkunde (DGZMK; German Society for Dental, Oral and Maxillofacial Surgery) and the Medical Faculty of the University of Heidelberg.

We thank the microarray unit of the DKFZ Genomics and Proteomics Core Facility for providing the Illumina Whole-Genome Expression Beadchips and related services.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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ESM 1

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High resolution image (TIFF 1839 kb)

References

  1. 1.
    Janson GR, De Luca CG, Martins DR, Henriques JF, De Freitas MR (2000) A radiographic comparison of apical root resorption after orthodontic treatment with 3 different fixed appliance techniques. Am J Orthod Dentofac Orthop 118(3):262–273CrossRefGoogle Scholar
  2. 2.
    Owman-Moll P, Kurol J, Lundgren D (1995) Repair of orthodontically induced root resorption in adolescents. Angle Orthod 65(6):403–408PubMedGoogle Scholar
  3. 3.
    Weltman B, Vig KW, Fields HW, Shanker S, Kaizar EE (2010) Root resorption associated with orthodontic tooth movement: a systematic review. Am J Orthod Dentofac Orthop 137(4):462–476, discussion 412ACrossRefGoogle Scholar
  4. 4.
    Rygh P (1972) Ultrastructural vascular changes in pressure zones of rat molar periodontium incident to orthodontic movement. Scand J Dent Res 80(4):307–321PubMedGoogle Scholar
  5. 5.
    von Bohl M, Kuijpers-Jagtman AM (2009) Hyalinization during orthodontic tooth movement: a systematic review on tissue reactions. Eur J Orthod 31(1):30–36CrossRefGoogle Scholar
  6. 6.
    Alhashimi N, Frithiof L, Brudvik P, Bakhiet M (2001) Orthodontic tooth movement and de novo synthesis of proinflammatory cytokines. Am J Orthod Dentofac Orthop 119(3):307–312CrossRefGoogle Scholar
  7. 7.
    Meikle MC (2006) The tissue, cellular, and molecular regulation of orthodontic tooth movement: 100 years after Carl Sandstedt. Eur J Orthod 28(3):221–240PubMedCrossRefGoogle Scholar
  8. 8.
    Diercke K, Konig A, Kohl A, Lux CJ, Erber R (2012) Human primary cementoblasts respond to combined IL-1beta stimulation and compression with an impaired BSP and CEMP-1 expression. Eur J Cell Biol 91(5):402–412PubMedCrossRefGoogle Scholar
  9. 9.
    Brezniak N, Wasserstein A (2002) Orthodontically induced inflammatory root resorption. Part II: the clinical aspects. Angle Orthod 72(2):180–184PubMedGoogle Scholar
  10. 10.
    Brezniak N, Wasserstein A (2002) Orthodontically induced inflammatory root resorption. Part I: the basic science aspects. Angle Orthod 72(2):175–179PubMedGoogle Scholar
  11. 11.
    Wolf M, Lossdorfer S, Craveiro R, Gotz W, Jager A (2013) Regulation of macrophage migration and activity by high-mobility group box 1 protein released from periodontal ligament cells during orthodontically induced periodontal repair: an in vitro and in vivo experimental study. J Orofac Orthop 74(5):420–434PubMedCrossRefGoogle Scholar
  12. 12.
    Wolf M, Lossdorfer S, Abuduwali N, Jager A (2013) Potential role of high mobility group box protein 1 and intermittent PTH (1-34) in periodontal tissue repair following orthodontic tooth movement in rats. Clin Oral Investig 17(3):989–997PubMedCrossRefGoogle Scholar
  13. 13.
    Proff P, Romer P (2009) The molecular mechanism behind bone remodelling: a review. Clin Oral Investig 13(4):355–362PubMedCrossRefGoogle Scholar
  14. 14.
    Tyrovola JB, Spyropoulos MN, Makou M, Perrea D (2008) Root resorption and the OPG/RANKL/RANK system: a mini review. J Oral Sci 50(4):367–376PubMedCrossRefGoogle Scholar
  15. 15.
    Yamaguchi M, Aihara N, Kojima T, Kasai K (2006) RANKL increase in compressed periodontal ligament cells from root resorption. J Dent Res 85(8):751–756PubMedCrossRefGoogle Scholar
  16. 16.
    de Araujo RM, Oba Y, Moriyama K (2007) Identification of genes related to mechanical stress in human periodontal ligament cells using microarray analysis. J Periodontal Res 42(1):15–22PubMedCrossRefGoogle Scholar
  17. 17.
    Kang KL, Lee SW, Ahn YS, Kim SH, Kang YG (2013) Bioinformatic analysis of responsive genes in two-dimension and three-dimension cultured human periodontal ligament cells subjected to compressive stress. J Periodontal Res 48(1):87–97PubMedCrossRefGoogle Scholar
  18. 18.
    Li Y, Li M, Tan L, Huang S, Zhao L, Tang T, Liu J, Zhao Z (2013) Analysis of time-course gene expression profiles of a periodontal ligament tissue model under compression. Arch Oral Biol 58(5):511–522PubMedCrossRefGoogle Scholar
  19. 19.
    Lee SK, Pi SH, Kim SH, Min KS, Lee HJ, Chang HS, Kang KH, Kim HR, Shin HI, Lee SK, Kim EC (2007) Substance P regulates macrophage inflammatory protein 3alpha/chemokine C-C ligand 20 (CCL20) with heme oxygenase-1 in human periodontal ligament cells. Clin Exp Immunol 150(3):567–575PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Li Y, Zheng W, Liu JS, Wang J, Yang P, Li ML, Zhao ZH (2011) Expression of osteoclastogenesis inducers in a tissue model of periodontal ligament under compression. J Dent Res 90(1):115–120PubMedCrossRefGoogle Scholar
  21. 21.
    D’Errico JA, Ouyang H, Berry JE, MacNeil RL, Strayhorn C, Imperiale MJ, Harris NL, Goldberg H, Somerman MJ (1999) Immortalized cementoblasts and periodontal ligament cells in culture. Bone 25(1):39–47PubMedCrossRefGoogle Scholar
  22. 22.
    Diercke K, Kohl A, Lux CJ, Erber R (2012) IL-1beta and compressive forces lead to a significant induction of RANKL-expression in primary human cementoblasts. J Orofac Orthop 73(5):397–412PubMedCrossRefGoogle Scholar
  23. 23.
    Grzesik WJ, Kuzentsov SA, Uzawa K, Mankani M, Robey PG, Yamauchi M (1998) Normal human cementum-derived cells: isolation, clonal expansion, and in vitro and in vivo characterization. J Bone Miner Res 13(10):1547–1554PubMedCrossRefGoogle Scholar
  24. 24.
    Kaneda T, Miyauchi M, Takekoshi T, Kitagawa S, Kitagawa M, Shiba H, Kurihara H, Takata T (2006) Characteristics of periodontal ligament subpopulations obtained by sequential enzymatic digestion of rat molar periodontal ligament. Bone 38(3):420–426PubMedCrossRefGoogle Scholar
  25. 25.
    Kitagawa M, Tahara H, Kitagawa S, Oka H, Kudo Y, Sato S, Ogawa I, Miyaichi M, Takata T (2006) Characterization of established cementoblast-like cell lines from human cementum-lining cells in vitro and in vivo. Bone 39(5):1035–1042PubMedCrossRefGoogle Scholar
  26. 26.
    Davidovitch Z (1991) Tooth movement. Crit Rev Oral Biol Med 2(4):411–450PubMedGoogle Scholar
  27. 27.
    Redlich M, Roos H, Reichenberg E, Zaks B, Grosskop A, Bar Kana I, Pitaru S, Palmon A (2004) The effect of centrifugal force on mRNA levels of collagenase, collagen type-I, tissue inhibitors of metalloproteinases and beta-actin in cultured human periodontal ligament fibroblasts. J Periodontal Res 39(1):27–32PubMedCrossRefGoogle Scholar
  28. 28.
    da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57CrossRefGoogle Scholar
  29. 29.
    da Huang W, Sherman BT, Lempicki RA (2009) Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res 37(1):1–13CrossRefPubMedCentralGoogle Scholar
  30. 30.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408PubMedCrossRefGoogle Scholar
  31. 31.
    Huang H, Hu ZZ, Arighi CN, Wu CH (2007) Integration of bioinformatics resources for functional analysis of gene expression and proteomic data. Front Biosci 12:5071–5088PubMedCrossRefGoogle Scholar
  32. 32.
    Kuppers R, Dalla-Favera R (2001) Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 20(40):5580–5594PubMedCrossRefGoogle Scholar
  33. 33.
    Krishnan V, Davidovitch Z (2006) Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofac Orthop 129(4):469 e461–432Google Scholar
  34. 34.
    Diercke K, Sen S, Kohl A, Lux CJ, Erber R (2011) Compression-dependent up-regulation of ephrin-A2 in PDL fibroblasts attenuates osteogenesis. J Dent ResGoogle Scholar
  35. 35.
    Bille ML, Thomsen B, Kjaer I (2011) Apoptosis in the human periodontal membrane evaluated in primary and permanent teeth. Acta Odontol Scand 69(6):385–388PubMedCrossRefGoogle Scholar
  36. 36.
    Lee JH, Lee DS, Nam H, Lee G, Seo BM, Cho YS, Bae HS, Park JC (2012) Dental follicle cells and cementoblasts induce apoptosis of ameloblast-lineage and Hertwig’s epithelial root sheath/epithelial rests of Malassez cells through the Fas-Fas ligand pathway. Eur J Oral Sci 120(1):29–37PubMedCrossRefGoogle Scholar
  37. 37.
    Glossop JR, Cartmell SH (2009) Effect of fluid flow-induced shear stress on human mesenchymal stem cells: differential gene expression of IL1B and MAP3K8 in MAPK signaling. Gene Expr Patterns: GEP 9(5):381–388PubMedCrossRefGoogle Scholar
  38. 38.
    Rana MW, Pothisiri V, Killiany DM, Xu XM (2001) Detection of apoptosis during orthodontic tooth movement in rats. Am J Orthod Dentofac Orthop 119(5):516–521CrossRefGoogle Scholar
  39. 39.
    Hao Y, Xu C, Sun SY, Zhang FQ (2009) Cyclic stretching force induces apoptosis in human periodontal ligament cells via caspase-9. Arch Oral Biol 54(9):864–870PubMedCrossRefGoogle Scholar
  40. 40.
    Ritter N, Mussig E, Steinberg T, Kohl A, Komposch G, Tomakidi P (2007) Elevated expression of genes assigned to NF-kappaB and apoptotic pathways in human periodontal ligament fibroblasts following mechanical stretch. Cell Tissue Res 328(3):537–548PubMedCrossRefGoogle Scholar
  41. 41.
    Zhong W, Xu C, Zhang F, Jiang X, Zhang X, Ye D (2008) Cyclic stretching force-induced early apoptosis in human periodontal ligament cells. Oral Dis 14(3):270–276PubMedCrossRefGoogle Scholar
  42. 42.
    Mabuchi R, Matsuzaka K, Shimono M (2002) Cell proliferation and cell death in periodontal ligaments during orthodontic tooth movement. J Periodontal Res 37(2):118–124PubMedCrossRefGoogle Scholar
  43. 43.
    Mitsui N, Suzuki N, Maeno M, Mayahara K, Yanagisawa M, Otsuka K, Shimizu N (2005) Optimal compressive force induces bone formation via increasing bone sialoprotein and prostaglandin E(2) production appropriately. Life Sci 77(25):3168–3182PubMedCrossRefGoogle Scholar
  44. 44.
    Kloostra PW, Eber RM, Inglehart MR (2007) Anxiety, stress, depression, and patients’ responses to periodontal treatment: periodontists’ knowledge and professional behavior. J Periodontol 78(1):64–71PubMedCrossRefGoogle Scholar
  45. 45.
    Rego EB, Inubushi T, Kawazoe A, Miyauchi M, Tanaka E, Takata T, Tanne K (2011) Effect of PGE induced by compressive and tensile stresses on cementoblast differentiation in vitro. Arch Oral Biol 56(11):1238–1246PubMedCrossRefGoogle Scholar
  46. 46.
    Romer P, Kostler J, Koretsi V, Proff P (2013) Endotoxins potentiate COX-2 and RANKL expression in compressed PDL cells. Clin Oral InvestigGoogle Scholar
  47. 47.
    Mada Y, Miyauchi M, Oka H, Kitagawa M, Sakamoto K, Iizuka S, Sato S, Noguchi K, Somerman MJ, Takata T (2006) Effects of endogenous and exogenous prostaglandin E2 on the proliferation and differentiation of a mouse cementoblast cell line (OCCM-30). J Periodontol 77(12):2051–2058PubMedCrossRefGoogle Scholar
  48. 48.
    Feijoo CG, Sarrazin AF, Allende ML, Glavic A (2009) Cystein-serine-rich nuclear protein 1, Axud1/Csrnp1, is essential for cephalic neural progenitor proliferation and survival in zebrafish. Dev Dyn 238(8):2034–2043PubMedCrossRefGoogle Scholar
  49. 49.
    Glavic A, Molnar C, Cotoras D, de Celis JF (2009) Drosophila Axud1 is involved in the control of proliferation and displays pro-apoptotic activity. Mech Dev 126(3–4):184–197PubMedCrossRefGoogle Scholar
  50. 50.
    Ishiguro H, Tsunoda T, Tanaka T, Fujii Y, Nakamura Y, Furukawa Y (2001) Identification of AXUD1, a novel human gene induced by AXIN1 and its reduced expression in human carcinomas of the lung, liver, colon and kidney. Oncogene 20(36):5062–5066PubMedCrossRefGoogle Scholar
  51. 51.
    Gingras S, Pelletier S, Boyd K, Ihle JN (2007) Characterization of a family of novel cysteine- serine-rich nuclear proteins (CSRNP). PLoS One 2(8):e808PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Inoue D, Kido S, Matsumoto T (2004) Transcriptional induction of FosB/DeltaFosB gene by mechanical stress in osteoblasts. J Biol Chem 279(48):49795–49803PubMedCrossRefGoogle Scholar
  53. 53.
    Matsumoto T, Kuriwaka-Kido R, Kondo T, Endo I, Kido S (2012) Regulation of osteoblast differentiation by interleukin-11 via AP-1 and Smad signaling. Endocr J 59(2):91–101PubMedCrossRefGoogle Scholar
  54. 54.
    Garlet TP, Coelho U, Repeke CE, Silva JS, Cunha Fde Q, Garlet GP (2008) Differential expression of osteoblast and osteoclast chemmoatractants in compression and tension sides during orthodontic movement. Cytokine 42(3):330–335PubMedCrossRefGoogle Scholar
  55. 55.
    Zhang J, Lu Y, Pienta KJ (2010) Multiple roles of chemokine (C-C motif) ligand 2 in promoting prostate cancer growth. J Natl Cancer Inst 102(8):522–528PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Asano M, Yamaguchi M, Nakajima R, Fujita S, Utsunomiya T, Yamamoto H, Kasai K (2011) IL-8 and MCP-1 induced by excessive orthodontic force mediates odontoclastogenesis in periodontal tissues. Oral Dis 17(5):489–498PubMedCrossRefGoogle Scholar
  57. 57.
    Cheriyath V, Glaser KB, Waring JF, Baz R, Hussein MA, Borden EC (2007) G1P3, an IFN-induced survival factor, antagonizes TRAIL-induced apoptosis in human myeloma cells. J Clin Invest 117(10):3107–3117PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Cheriyath V, Kuhns MA, Jacobs BS, Evangelista P, Elson P, Downs-Kelly E, Tubbs R, Borden EC (2012) G1P3, an interferon- and estrogen-induced survival protein contributes to hyperplasia, tamoxifen resistance and poor outcomes in breast cancer. Oncogene 31(17):2222–2236PubMedCrossRefGoogle Scholar
  59. 59.
    Brenneis C, Coste O, Altenrath K, Angioni C, Schmidt H, Schuh CD, Zhang DD, Henke M, Weigert A, Brune B, Rubin B, Nusing R, Scholich K, Geisslinger G (2011) Anti-inflammatory role of microsomal prostaglandin E synthase-1 in a model of neuroinflammation. J Biol Chem 286(3):2331–2342PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Korotkova M, Daha NA, Seddighzadeh M, Ding B, Catrina AI, Lindblad S, Huizinga TW, Toes RE, Alfredsson L, Klareskog L, Jakobsson PJ, Padyukov L (2011) Variants of gene for microsomal prostaglandin E2 synthase show association with disease and severe inflammation in rheumatoid arthritis. Eur J Hum Genet 19(8):908–914PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Lammerding J, Kamm RD, Lee RT (2004) Mechanotransduction in cardiac myocytes. Ann N Y Acad Sci 1015:53–70PubMedCrossRefGoogle Scholar
  62. 62.
    Wang JH, Thampatty BP, Lin JS, Im HJ (2007) Mechanoregulation of gene expression in fibroblasts. Gene 391(1–2):1–15PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Tang L, Zhou XD, Wang Q, Zhang L, Wang Y, Li XY, Huang DM (2011) Expression of TRAF6 and pro-inflammatory cytokines through activation of TLR2, TLR4, NOD1, and NOD2 in human periodontal ligament fibroblasts. Arch Oral Biol 56(10):1064–1072PubMedCrossRefGoogle Scholar
  64. 64.
    Uehara A, Takada H (2007) Functional TLRs and NODs in human gingival fibroblasts. J Dent Res 86(3):249–254PubMedCrossRefGoogle Scholar
  65. 65.
    Liu C, Zhao Y, Cheung WY, Gandhi R, Wang L, You L (2010) Effects of cyclic hydraulic pressure on osteocytes. Bone 46(5):1449–1456PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Arlt A, Schafer H (2011) Role of the immediate early response 3 (IER3) gene in cellular stress response, inflammation and tumorigenesis. Eur J Cell Biol 90(6–7):545–552PubMedCrossRefGoogle Scholar
  67. 67.
    Wu MX (2003) Roles of the stress-induced gene IEX-1 in regulation of cell death and oncogenesis. Apoptosis: Int J Program Cell Death 8(1):11–18CrossRefGoogle Scholar
  68. 68.
    Dalal S, Foster CR, Das BC, Singh M, Singh K (2012) Beta-adrenergic receptor stimulation induces endoplasmic reticulum stress in adult cardiac myocytes: role in apoptosis. Mol Cell Biochem 364(1–2):59–70PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Hassan S, Karpova Y, Baiz D, Yancey D, Pullikuth A, Flores A, Register T, Cline JM, D’Agostino R Jr, Danial N, Datta SR, Kulik G (2013) Behavioral stress accelerates prostate cancer development in mice. J Clin Invest 123(2):874–886PubMedPubMedCentralGoogle Scholar
  70. 70.
    Salojin K, Oravecz T (2007) Regulation of innate immunity by MAPK dual-specificity phosphatases: knockout models reveal new tricks of old genes. J Leukoc Biol 81(4):860–869PubMedCrossRefGoogle Scholar
  71. 71.
    Gonzalez YR, Zhang Y, Behzadpoor D, Cregan S, Bamforth S, Slack RS, Park DS (2008) CITED2 signals through peroxisome proliferator-activated receptor-gamma to regulate death of cortical neurons after DNA damage. J Neurosci: Off J Soc Neurosci 28(21):5559–5569CrossRefGoogle Scholar
  72. 72.
    Yoshida T, Sekine T, Aisaki K, Mikami T, Kanno J, Okayasu I (2011) CITED2 is activated in ulcerative colitis and induces p53-dependent apoptosis in response to butyric acid. J Gastroenterol 46(3):339–349PubMedCrossRefGoogle Scholar
  73. 73.
    Lin MT, Juan CY, Chang KJ, Chen WJ, Kuo ML (2001) IL-6 inhibits apoptosis and retains oxidative DNA lesions in human gastric cancer AGS cells through up-regulation of anti-apoptotic gene mcl-1. Carcinogenesis 22(12):1947–1953PubMedCrossRefGoogle Scholar
  74. 74.
    Moodley YP, Misso NL, Scaffidi AK, Fogel-Petrovic M, McAnulty RJ, Laurent GJ, Thompson PJ, Knight DA (2003) Inverse effects of interleukin-6 on apoptosis of fibroblasts from pulmonary fibrosis and normal lungs. Am J Respir Cell Mol Biol 29(4):490–498PubMedCrossRefGoogle Scholar
  75. 75.
    Sato Y (2001) Role of ETS family transcription factors in vascular development and angiogenesis. Cell Struct Funct 26(1):19–24PubMedCrossRefGoogle Scholar
  76. 76.
    Seth A, Watson DK (2005) ETS transcription factors and their emerging roles in human cancer. Eur J Cancer 41(16):2462–2478PubMedCrossRefGoogle Scholar
  77. 77.
    Berry FB, Skarie JM, Mirzayans F, Fortin Y, Hudson TJ, Raymond V, Link BA, Walter MA (2008) FOXC1 is required for cell viability and resistance to oxidative stress in the eye through the transcriptional regulation of FOXO1A. Hum Mol Genet 17(4):490–505PubMedCrossRefGoogle Scholar
  78. 78.
    Galli C, Passeri G, Macaluso GM (2011) FoxOs, Wnts and oxidative stress-induced bone loss: new players in the periodontitis arena? J Periodontal Res 46(4):397–406PubMedCrossRefGoogle Scholar
  79. 79.
    Regula KM, Ens K, Kirshenbaum LA (2002) IKK beta is required for Bcl-2-mediated NF-kappa B activation in ventricular myocytes. J Biol Chem 277(41):38676–38682PubMedCrossRefGoogle Scholar
  80. 80.
    Pasqualucci L, Bereshchenko O, Niu H, Klein U, Basso K, Guglielmino R, Cattoretti G, Dalla-Favera R (2003) Molecular pathogenesis of non-Hodgkin’s lymphoma: the role of Bcl-6. Leuk Lymphoma 44(Suppl 3):S5–S12PubMedCrossRefGoogle Scholar
  81. 81.
    Li N, Zheng Y, Chen W, Wang C, Liu X, He W, Xu H, Cao X (2007) Adaptor protein LAPF recruits phosphorylated p53 to lysosomes and triggers lysosomal destabilization in apoptosis. Cancer Res 67(23):11176–11185PubMedCrossRefGoogle Scholar
  82. 82.
    Bidzhekov K, Zernecke A, Weber C (2006) MCP-1 induces a novel transcription factor with proapoptotic activity. Circ Res 98(9):1107–1109PubMedCrossRefGoogle Scholar
  83. 83.
    He YY, He XJ, Guo PF, Du MR, Shao J, Li MQ, Li DJ (2012) The decidual stromal cells-secreted CCL2 induces and maintains decidual leukocytes into Th2 bias in human early pregnancy. Clin Immunol 145(2):161–173PubMedCrossRefGoogle Scholar
  84. 84.
    Lin H, Zhang Y, Wang H, Xu D, Meng X, Shao Y, Lin C, Ye Y, Qian H, Wang S (2012) Tissue inhibitor of metalloproteinases-3 transfer suppresses malignant behaviors of colorectal cancer cells. Cancer Gene Ther 19(12):845–851PubMedCrossRefGoogle Scholar
  85. 85.
    Delhalle S, Deregowski V, Benoit V, Merville MP, Bours V (2002) NF-kappaB-dependent MnSOD expression protects adenocarcinoma cells from TNF-alpha-induced apoptosis. Oncogene 21(24):3917–3924PubMedCrossRefGoogle Scholar
  86. 86.
    Sutton G, Madigan M, Roufas A, McAvoy J (2010) Secreted frizzled-related protein 1 (SFRP1) is highly upregulated in keratoconus epithelium: a novel finding highlighting a new potential focus for keratoconus research and treatment. Clin Exp Ophthalmol 38(1):43–48CrossRefGoogle Scholar
  87. 87.
    Basseres DS, Baldwin AS (2006) Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene 25(51):6817–6830PubMedCrossRefGoogle Scholar
  88. 88.
    Nikolaev A, McLaughlin T, O’Leary DD, Tessier-Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457(7232):981–989PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Burton TR, Gibson SB (2009) The role of Bcl-2 family member BNIP3 in cell death and disease: NIPping at the heels of cell death. Cell Death Differ 16(4):515–523PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Zoller M (2011) CD44: can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer 11(4):254–267PubMedCrossRefGoogle Scholar
  91. 91.
    Hendriksen PJ, Dits NF, Kokame K, Veldhoven A, van Weerden WM, Bangma CH, Trapman J, Jenster G (2006) Evolution of the androgen receptor pathway during progression of prostate cancer. Cancer Res 66(10):5012–5020PubMedCrossRefGoogle Scholar
  92. 92.
    Kim HS, Lee MS (2007) STAT1 as a key modulator of cell death. Cell Signal 19(3):454–465PubMedCrossRefGoogle Scholar
  93. 93.
    Fleischer A, Rebollo A (2004) Induction of p53-independent apoptosis by the BH3-only protein ITM2Bs. FEBS Lett 557(1–3):283–287PubMedCrossRefGoogle Scholar
  94. 94.
    Benedict CA, Ware CF (2012) TRAIL: not just for tumors anymore? J Exp Med 209(11):1903–1906PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Dorn GW 2nd, Diwan A (2008) The rationale for cardiomyocyte resuscitation in myocardial salvage. J Mol Med (Berl) 86(10):1085–1095CrossRefGoogle Scholar
  96. 96.
    Gunshin H, Fujiwara Y, Custodio AO, Direnzo C, Robine S, Andrews NC (2005) Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver. J Clin Invest 115(5):1258–1266PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Katja Diercke
    • 1
    Email author
  • Sebastian Zingler
    • 1
  • Annette Kohl
    • 1
  • Christopher J. Lux
    • 1
  • Ralf Erber
    • 1
  1. 1.HeidelbergGermany

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