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Amino Acids

, Volume 46, Issue 3, pp 717–728 | Cite as

Polyamine delivery as a tool to modulate stem cell differentiation in skeletal tissue engineering

  • Rosa Maria Borzì
  • Serena Guidotti
  • Manuela Minguzzi
  • Annalisa Facchini
  • Daniela Platano
  • Giovanni Trisolino
  • Giuseppe Filardo
  • Silvia Cetrullo
  • Stefania D’Adamo
  • Claudio Stefanelli
  • Andrea Facchini
  • Flavio FlamigniEmail author
Mini review Article

Abstract

The first step in skeleton development is the condensation of mesenchymal precursors followed by any of two different types of ossification, depending on the type of bone segment: in intramembranous ossification, the bone is deposed directly in the mesenchymal anlagen, whereas in endochondral ossification, the bone is deposed onto a template of cartilage that is subsequently substituted by bone. Polyamines and polyamine-related enzymes have been implicated in bone development as global regulators of the transcriptional and translational activity of stem cells and pivotal transcription factors. Therefore, it is tempting to investigate their use as a tool to improve regenerative medicine strategies in orthopedics. Growing evidence in vitro suggests a role for polyamines in enhancing differentiation in both adult stem cells and differentiated chondrocytes. Adipose-derived stem cells have recently proved to be a convenient alternative to bone marrow stromal cells, due to their easy accessibility and the high frequency of stem cell precursors per volume unit. State-of-the-art “prolotherapy” approaches for skeleton regeneration include the use of adipose-derived stem cells and platelet concentrates, such as platelet-rich plasma (PRP). Besides several growth factors, PRP also contains polyamines in the micromolar range, which may also exert an anti-apoptotic effect, thus helping to explain the efficacy of PRP in enhancing osteogenesis in vitro and in vivo. On the other hand, spermidine and spermine are both able to enhance hypertrophy and terminal differentiation of chondrocytes and therefore appear to be inducers of endochondral ossification. Finally, the peculiar activity of spermidine as an inducer of autophagy suggests the possibility of exploiting its use to enhance this cytoprotective mechanism to counteract the degenerative changes underlying either the aging or degenerative diseases that affect bone or cartilage.

Keywords

Polyamines Adipose-derived stem cells Skeleton development Osteogenesis Apoptosis 

Notes

Acknowledgments

This work was supported by FIRB (Ministero dell’Istruzione, dell’Università e della Ricerca, Italy) grant RBAP10KCNS and Fondi cinque per mille (Ministero della Salute, Italy). The authors wish to thank Dr. Maddalena Zini (Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, Bologna, Italy) for technical assistance and Keith Smith for revising the English language.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Aeschlimann D, Wetterwald A, Fleisch H, Paulsson M (1993) Expression of tissue transglutaminase in skeletal tissues correlates with events of terminal differentiation of chondrocytes. J Cell Biol 120(6):1461–1470PubMedCrossRefGoogle Scholar
  2. Aigner T, Haag J, Zimmer R (2007) Functional genomics, evo-devo and systems biology: a chance to overcome complexity? Curr Opin Rheumatol 19(5):463–470. doi: 10.1097/BOR.0b013e3282bf6c68 PubMedCrossRefGoogle Scholar
  3. Alm K, Berntsson P, Oredsson SM (1999) Topoisomerase II is nonfunctional in polyamine-depleted cells. J Cell Biochem 75(1):46–55. doi: 10.1002/(SICI)1097-4644(19991001)75:1<46:AID-JCB5>3.0.CO;2-N PubMedCrossRefGoogle Scholar
  4. Amini AR, Laurencin CT, Nukavarapu SP (2012) Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 40(5):363–408PubMedCentralPubMedCrossRefGoogle Scholar
  5. Attur MG, Dave M, Akamatsu M, Katoh M, Amin AR (2002) Osteoarthritis or osteoarthrosis: the definition of inflammation becomes a semantic issue in the genomic era of molecular medicine. Osteoarthr Cartil 10(1):1–4. doi: 10.1053/joca.2001.0488 PubMedCrossRefGoogle Scholar
  6. Bargoni N, Tazartes O (1988) Polyamines and enzymes of polyamines metabolism in the cartilage during embryonic development. Int J Biochem 20(3):317–319PubMedCrossRefGoogle Scholar
  7. Bennetzen MV, Marino G, Pultz D, Morselli E, Faergeman NJ, Kroemer G, Andersen JS (2012) Phosphoproteomic analysis of cells treated with longevity-related autophagy inducers. Cell Cycle 11(9):1827–1840. doi: 10.4161/cc.20233 PubMedCrossRefGoogle Scholar
  8. Borzi RM, Mazzetti I, Macor S, Silvestri T, Bassi A, Cattini L, Facchini A (1999) Flow cytometric analysis of intracellular chemokines in chondrocytes in vivo: constitutive expression and enhancement in osteoarthritis and rheumatoid arthritis. FEBS Lett 455(3):238–242PubMedCrossRefGoogle Scholar
  9. Casero RA Jr, Marton LJ (2007) Targeting polyamine metabolism and function in cancer and other hyperproliferative diseases. Nat Rev Drug Discov 6(5):373–390PubMedCrossRefGoogle Scholar
  10. Cason AL, Ikeguchi Y, Skinner C, Wood TC, Holden KR, Lubs HA, Martinez F, Simensen RJ, Stevenson RE, Pegg AE, Schwartz CE (2003) X-linked spermine synthase gene (SMS) defect: the first polyamine deficiency syndrome. Eur J Hum Genet 11(12):937–944. doi: 10.1038/sj.ejhg.5201072 PubMedCrossRefGoogle Scholar
  11. Cervelli M, Amendola R, Polticelli F, Mariottini P (2012) Spermine oxidase: ten years after. Amino Acids 42(2–3):441–450. doi: 10.1007/s00726-011-1014-z PubMedCrossRefGoogle Scholar
  12. Chen HT, Lee MJ, Chen CH, Chuang SC, Chang LF, Ho ML, Hung SH, Fu YC, Wang YH, Wang HI, Wang GJ, Kang L, Chang JK (2012) Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures. J Cell Mol Med 16(3):582–593. doi: 10.1111/j.1582-4934.2011.01335.x PubMedCrossRefGoogle Scholar
  13. Childs AC, Mehta DJ, Gerner EW (2003) Polyamine-dependent gene expression. Cell Mol Life Sci 60(7):1394–1406. doi: 10.1007/s00018-003-2332-4 PubMedCrossRefGoogle Scholar
  14. Cooper KD, Shukla JB, Rennert OM (1976) Polyamine distribution in cellular compartments of blood and in aging erythrocytes. Clin Chim Acta 73(1):71–88PubMedCrossRefGoogle Scholar
  15. Cordella-Miele E, Miele L, Beninati S, Mukherjee AB (1993) Transglutaminase-catalyzed incorporation of polyamines into phospholipase A2. J Biochem 113(2):164–173PubMedGoogle Scholar
  16. Dejica VM, Mort JS, Laverty S, Antoniou J, Zukor DJ, Tanzer M, Poole AR (2012) Increased type II collagen cleavage by cathepsin K and collagenase activities with aging and osteoarthritis in human articular cartilage. Arthr Res Ther 14(3):R113. doi: 10.1186/ar3839 CrossRefGoogle Scholar
  17. Drissi H, Zuscik M, Rosier R, O’Keefe R (2005) Transcriptional regulation of chondrocyte maturation: potential involvement of transcription factors in OA pathogenesis. Mol Aspects Med 26(3):169–179PubMedCrossRefGoogle Scholar
  18. Estes BT, Wu AW, Storms RW, Guilak F (2006) Extended passaging, but not aldehyde dehydrogenase activity, increases the chondrogenic potential of human adipose-derived adult stem cells. J Cell Physiol 209(3):987–995. doi: 10.1002/jcp.20808 PubMedCrossRefGoogle Scholar
  19. Facchini A, Borzi RM, Marcu KB, Stefanelli C, Olivotto E, Goldring MB, Flamigni F (2005) Polyamine depletion inhibits NF-kappaB binding to DNA and interleukin-8 production in human chondrocytes stimulated by tumor necrosis factor-alpha. J Cell Physiol 204(3):956–963. doi: 10.1002/jcp.20368 PubMedCentralPubMedCrossRefGoogle Scholar
  20. Facchini A, Borzi RM, Olivotto E, Platano D, Pagani S, Cetrullo S, Flamigni F (2012) Role of polyamines in hypertrophy and terminal differentiation of osteoarthritic chondrocytes. Amino Acids 42(2–3):667–678. doi: 10.1007/s00726-011-1041-9 PubMedCrossRefGoogle Scholar
  21. Flamigni F, Stanic I, Facchini A, Cetrullo S, Tantini B, Borzi RM, Guarnieri C, Caldarera CM (2007) Polyamine biosynthesis as a target to inhibit apoptosis of non-tumoral cells. Amino Acids 33(2):197–202PubMedCrossRefGoogle Scholar
  22. Gauci SJ, Golub SB, Tutolo L, Little CB, Sims NA, Lee ER, Mackie EJ, Fosang AJ (2008) Modulating chondrocyte hypertrophy in growth plate and osteoarthritic cartilage. J Musculoskelet Neuronal Interact 8(4):308–310PubMedGoogle Scholar
  23. Gimble JM, Bunnell BA, Guilak F (2012) Human adipose-derived cells: an update on the transition to clinical translation. Regen Med 7(2):225–235. doi: 10.2217/rme.11.119 PubMedCentralPubMedCrossRefGoogle Scholar
  24. Goldring MB, Tsuchimochi K, Ijiri K (2006) The control of chondrogenesis. J Cell Biochem 97(1):33–44PubMedCrossRefGoogle Scholar
  25. Guidotti S, Facchini A, Platano D, Olivotto E, Minguzzi M, Trisolino G, Filardo G, Cetrullo S, Tantini B, Martucci E, Flamigni F, Borzi RM (2013) Enhanced osteoblastogenesis of adipose-derived stem cells on spermine delivery via beta-catenin activation. Stem Cells Dev. doi: 10.1089/scd.2012.0399 PubMedGoogle Scholar
  26. Han L, Xu C, Jiang C, Li H, Zhang W, Zhao Y, Zhang L, Zhang Y, Zhao W, Yang B (2007) Effects of polyamines on apoptosis induced by simulated ischemia/reperfusion injury in cultured neonatal rat cardiomyocytes. Cell Biol Int 31(11):1345–1352. doi: 10.1016/j.cellbi.2007.05.015 PubMedCrossRefGoogle Scholar
  27. Hartmann C (2006) A Wnt canon orchestrating osteoblastogenesis. Trends Cell Biol 16(3):151–158. doi: 10.1016/j.tcb.2006.01.001 PubMedCrossRefGoogle Scholar
  28. Heath DJ, Downes S, Verderio E, Griffin M (2001) Characterization of tissue transglutaminase in human osteoblast-like cells. J Bone Miner Res 16(8):1477–1485. doi: 10.1359/jbmr.2001.16.8.1477 PubMedCrossRefGoogle Scholar
  29. Hildner F, Albrecht C, Gabriel C, Redl H, van Griensven M (2011) State of the art and future perspectives of articular cartilage regeneration: a focus on adipose-derived stem cells and platelet-derived products. J Tissue Eng Regen Med 5(4):e36–e51. doi: 10.1002/term.386 PubMedCrossRefGoogle Scholar
  30. Hu H, Hilton MJ, Tu X, Yu K, Ornitz DM, Long F (2005) Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development 132(1):49–60. doi: 10.1242/dev.01564 PubMedCrossRefGoogle Scholar
  31. Igarashi K, Kashiwagi K (2011) Characterization of genes for polyamine modulon. Methods Mol Biol 720:51–65. doi: 10.1007/978-1-61779-034-8_3 PubMedCrossRefGoogle Scholar
  32. James AW, Levi B, Nelson ER, Peng M, Commons GW, Lee M, Wu B, Longaker MT (2011) Deleterious effects of freezing on osteogenic differentiation of human adipose-derived stromal cells in vitro and in vivo. Stem Cells Dev 20(3):427–439. doi: 10.1089/scd.2010.0082 PubMedCrossRefGoogle Scholar
  33. Janne J, Alhonen L, Pietila M, Keinanen TA (2004) Genetic approaches to the cellular functions of polyamines in mammals. Eur J Biochem 271(5):877–894PubMedCrossRefGoogle Scholar
  34. Johnson KA, Terkeltaub RA (2005) External GTP-bound transglutaminase 2 is a molecular switch for chondrocyte hypertrophic differentiation and calcification. J Biol Chem 280(15):15004–15012. doi: 10.1074/jbc.M500962200 PubMedCrossRefGoogle Scholar
  35. Jurgens WJ, van Dijk A, Doulabi BZ, Niessen FB, Ritt MJ, van Milligen FJ, Helder MN (2009) Freshly isolated stromal cells from the infrapatellar fat pad are suitable for a one-step surgical procedure to regenerate cartilage tissue. Cytotherapy 11(8):1052–1064. doi: 10.3109/14653240903219122 PubMedCrossRefGoogle Scholar
  36. Karouzakis E, Gay RE, Gay S, Neidhart M (2012) Increased recycling of polyamines is associated with global DNA hypomethylation in rheumatoid arthritis synovial fibroblasts. Arthr Rheum 64(6):1809–1817. doi: 10.1002/art.34340 CrossRefGoogle Scholar
  37. Knudson CB, Knudson W (2001) Cartilage proteoglycans. Semin Cell Dev Biol 12(2):69–78. doi: 10.1006/scdb.2000.0243 PubMedCrossRefGoogle Scholar
  38. Kobayashi T, Kronenberg H (2005) Minireview: transcriptional regulation in development of bone. Endocrinology 146(3):1012–1017. doi: 10.1210/en.2004-1343 PubMedCrossRefGoogle Scholar
  39. Komori T (2006) Regulation of osteoblast differentiation by transcription factors. J Cell Biochem 99(5):1233–1239. doi: 10.1002/jcb.20958 PubMedCrossRefGoogle Scholar
  40. Kon E, Filardo G, Di Martino A, Marcacci M (2011) Platelet-rich plasma (PRP) to treat sports injuries: evidence to support its use. Knee Surg Sports Traumatol Arthrosc 19(4):516–527. doi: 10.1007/s00167-010-1306-y PubMedCrossRefGoogle Scholar
  41. Korhonen VP, Niiranen K, Halmekyto M, Pietila M, Diegelman P, Parkkinen JJ, Eloranta T, Porter CW, Alhonen L, Janne J (2001) Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs. Mol Pharmacol 59(2):231–238PubMedGoogle Scholar
  42. Kroeze RJ, Knippenberg M, Helder MN (2011) Osteogenic differentiation strategies for adipose-derived mesenchymal stem cells. Methods Mol Biol 702:233–248. doi: 10.1007/978-1-61737-960-4_17 PubMedCrossRefGoogle Scholar
  43. Lee K, Kim H, Kim JM, Kim JR, Kim KJ, Kim YJ, Park SI, Jeong JH, Moon YM, Lim HS, Bae DW, Kwon J, Ko CY, Kim HS, Shin HI, Jeong D (2011) Systemic transplantation of human adipose-derived stem cells stimulates bone repair by promoting osteoblast and osteoclast function. J Cell Mol Med 15(10):2082–2094. doi: 10.1111/j.1582-4934.2010.01230.x PubMedCrossRefGoogle Scholar
  44. Lotz MK, Carames B (2011) Autophagy and cartilage homeostasis mechanisms in joint health, aging and OA. Nat Rev Rheumatol 7(10):579–587. doi: 10.1038/nrrheum.2011.109 PubMedCentralPubMedGoogle Scholar
  45. Mackie EJ, Ahmed YA, Tatarczuch L, Chen KS, Mirams M (2008) Endochondral ossification: how cartilage is converted into bone in the developing skeleton. Int J Biochem Cell Biol 40(1):46–62. doi: 10.1016/j.biocel.2007.06.009 PubMedCrossRefGoogle Scholar
  46. Mariani E, Facchini A (2012) Clinical applications and biosafety of human adult mesenchymal stem cells. Curr Pharm Des 18(13):1821–1845PubMedCrossRefGoogle Scholar
  47. Marino G, Morselli E, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Benit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, Lopez-Otin C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G (2011) Longevity-relevant regulation of autophagy at the level of the acetylproteome. Autophagy 7(6):647–649PubMedCrossRefGoogle Scholar
  48. Meissen JK, Yuen BT, Kind T, Riggs JW, Barupal DK, Knoepfler PS, Fiehn O (2012) Induced pluripotent stem cells show metabolomic differences to embryonic stem cells in polyunsaturated phosphatidylcholines and primary metabolism. PLoS ONE 7(10):e46770. doi: 10.1371/journal.pone.0046770 PubMedCentralPubMedCrossRefGoogle Scholar
  49. Merz D, Liu R, Johnson K, Terkeltaub R (2003) IL-8/CXCL8 and growth-related oncogene alpha/CXCL1 induce chondrocyte hypertrophic differentiation. J Immunol 171(8):4406–4415PubMedGoogle Scholar
  50. Minois N, Carmona-Gutierrez D, Madeo F (2011) Polyamines in aging and disease. Aging (Albany NY) 3(8):716–732Google Scholar
  51. Nakashima K, de Crombrugghe B (2003) Transcriptional mechanisms in osteoblast differentiation and bone formation. Trends Genet 19(8):458–466. doi: 10.1016/S0168-9525(03)00176-8 PubMedCrossRefGoogle Scholar
  52. Nurminskaya M, Kaartinen MT (2006) Transglutaminases in mineralized tissues. Front Biosci 11:1591–1606PubMedCrossRefGoogle Scholar
  53. Olivotto E, Borzi RM, Vitellozzi R, Pagani S, Facchini A, Battistelli M, Penzo M, Li X, Flamigni F, Li J, Falcieri E, Facchini A, Marcu KB (2008) Differential requirements for IKKalpha and IKKbeta in the differentiation of primary human osteoarthritic chondrocytes. Arthr Rheum 58(1):227–239CrossRefGoogle Scholar
  54. Orlandi A, Oliva F, Taurisano G, Candi E, Di Lascio A, Melino G, Spagnoli LG, Tarantino U (2009) Transglutaminase-2 differently regulates cartilage destruction and osteophyte formation in a surgical model of osteoarthritis. Amino Acids 36(4):755–763. doi: 10.1007/s00726-008-0129-3 PubMedCrossRefGoogle Scholar
  55. Pegg AE (2008) Spermidine/spermine-N(1)-acetyltransferase: a key metabolic regulator. Am J Physiol Endocrinol Metab 294(6):E995–1010. doi: 10.1152/ajpendo.90217.2008 PubMedCrossRefGoogle Scholar
  56. Pendeville H, Carpino N, Marine JC, Takahashi Y, Muller M, Martial JA, Cleveland JL (2001) The ornithine decarboxylase gene is essential for cell survival during early murine development. Mol Cell Biol 21(19):6549–6558PubMedCentralPubMedCrossRefGoogle Scholar
  57. Perez-Leal O, Barrero CA, Clarkson AB, Casero RA Jr, Merali S (2012) Polyamine-regulated translation of spermidine/spermine-N1-acetyltransferase. Mol Cell Biol 32(8):1453–1467. doi: 10.1128/MCB.06444-11 PubMedCentralPubMedCrossRefGoogle Scholar
  58. Poulin R, Casero RA, Soulet D (2012) Recent advances in the molecular biology of metazoan polyamine transport. Amino Acids 42(2–3):711–723. doi: 10.1007/s00726-011-0987-y PubMedCentralPubMedCrossRefGoogle Scholar
  59. Pucciarelli S, Moreschini B, Micozzi D, De Fronzo GS, Carpi FM, Polzonetti V, Vincenzetti S, Mignini F, Napolioni V (2012) Spermidine and spermine are enriched in whole blood of nona/centenarians. Rejuvenation Res 15(6):590–595. doi: 10.1089/rej.2012.1349 PubMedCrossRefGoogle Scholar
  60. Pulsatelli L, Dolzani P, Piacentini A, Silvestri T, Ruggeri R, Gualtieri G, Meliconi R, Facchini A (1999) Chemokine production by human chondrocytes. J Rheumatol 26(9):1992–2001PubMedGoogle Scholar
  61. Rath NC, Reddi AH (1981) Changes in polyamines, RNA synthesis, and cell proliferation during matrix-induced cartilage, bone, and bone marrow development. Dev Biol 82(2):211–216PubMedCrossRefGoogle Scholar
  62. Rider JE, Hacker A, Mackintosh CA, Pegg AE, Woster PM, Casero RA Jr (2007) Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide. Amino Acids 33(2):231–240. doi: 10.1007/s00726-007-0513-4 PubMedCrossRefGoogle Scholar
  63. Roldan M, Macias-Gonzalez M, Garcia R, Tinahones FJ, Martin M (2011) Obesity short-circuits stemness gene network in human adipose multipotent stem cells. FASEB J 25(12):4111–4126. doi: 10.1096/fj.10-171439 PubMedCrossRefGoogle Scholar
  64. Sanchez-Gonzalez DJ, Mendez-Bolaina E, Trejo-Bahena NI (2012) Platelet-rich plasma peptides: key for regeneration. Int J Pept 2012:532519. doi: 10.1155/2012/532519 PubMedCentralPubMedGoogle Scholar
  65. Santo VE, Gomes ME, Mano JF, Reis RL (2013) Controlled release strategies for bone, cartilage, and osteochondral engineering-part II: challenges on the evolution from single to multiple bioactive factor delivery. Tissue Eng Part B Rev. doi: 10.1089/ten.TEB.2012.0727 Google Scholar
  66. Scotti C, Tonnarelli B, Papadimitropoulos A, Scherberich A, Schaeren S, Schauerte A, Lopez-Rios J, Zeller R, Barbero A, Martin I (2010) Recapitulation of endochondral bone formation using human adult mesenchymal stem cells as a paradigm for developmental engineering. Proc Natl Acad Sci USA 107(16):7251–7256. doi: 10.1073/pnas.1000302107 PubMedCrossRefGoogle Scholar
  67. Scotti C, Piccinini E, Takizawa H, Todorov A, Bourgine P, Papadimitropoulos A, Barbero A, Manz MG, Martin I (2013) Engineering of a functional bone organ through endochondral ossification. Proc Natl Acad Sci USA 110(10):3997–4002. doi: 10.1073/pnas.1220108110 PubMedCrossRefGoogle Scholar
  68. Sen B, Xie Z, Case N, Ma M, Rubin C, Rubin J (2008) Mechanical strain inhibits adipogenesis in mesenchymal stem cells by stimulating a durable beta-catenin signal. Endocrinology 149(12):6065–6075. doi: 10.1210/en.2008-0687 PubMedCrossRefGoogle Scholar
  69. Stefanelli C, Pignatti C, Tantini B, Fattori M, Stanic I, Mackintosh CA, Flamigni F, Guarnieri C, Caldarera CM, Pegg AE (2001) Effect of polyamine depletion on caspase activation: a study with spermine synthase-deficient cells. Biochem J 355(Pt 1):199–206PubMedCrossRefGoogle Scholar
  70. Takano T, Takigawa M, Suzuki F (1981) Role of polyamines in expression of the differentiated phenotype of chondrocytes in culture. Med Biol 59(5–6):423–427PubMedGoogle Scholar
  71. Takano T, Takigawa M, Suzuki F (1983) Role of polyamines in expression of the differentiated phenotype of chondrocytes: effect of dl-alpha-hydrazino-delta-aminovaleric acid (dl-HAVA), an inhibitor of ornithine decarboxylase, on chondrocytes treated with parathyroid hormone. J Biochem 93(2):591–598PubMedGoogle Scholar
  72. Takigawa M, Takano T, Suzuki F (1981) Effects of parathyroid hormone and cyclic AMP analogues on the activity of ornithine decarboxylase and expression of the differentiated phenotype of chondrocytes in culture. J Cell Physiol 106(2):259–268PubMedCrossRefGoogle Scholar
  73. Tarantino U, Ferlosio A, Arcuri G, Spagnoli LG, Orlandi A (2013) Transglutaminase 2 as a biomarker of osteoarthritis: an update. Amino Acids 44(1):199–207. doi: 10.1007/s00726-011-1181-y PubMedCrossRefGoogle Scholar
  74. Teplyuk NM, Haupt LM, Ling L, Dombrowski C, Mun FK, Nathan SS, Lian JB, Stein JL, Stein GS, Cool SM, van Wijnen AJ (2009) The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts. J Cell Biochem 107(1):144–154. doi: 10.1002/jcb.22108 PubMedCentralPubMedCrossRefGoogle Scholar
  75. Tjabringa GS, Vezeridis PS, Zandieh-Doulabi B, Helder MN, Wuisman PI, Klein-Nulend J (2006) Polyamines modulate nitric oxide production and COX-2 gene expression in response to mechanical loading in human adipose tissue-derived mesenchymal stem cells. Stem Cells 24(10):2262–2269. doi: 10.1634/stemcells.2005-0625 PubMedCrossRefGoogle Scholar
  76. Tjabringa GS, Zandieh-Doulabi B, Helder MN, Knippenberg M, Wuisman PI, Klein-Nulend J (2008) The polymine spermine regulates osteogenic differentiation in adipose stem cells. J Cell Mol Med 12(5A):1710–1717. doi: 10.1111/j.1582-4934.2008.00224.x PubMedCrossRefGoogle Scholar
  77. Tollervey JR, Lunyak VV (2012) Epigenetics: judge, jury and executioner of stem cell fate. Epigenetics 7(8):823–840. doi: 10.4161/epi.21141 PubMedCrossRefGoogle Scholar
  78. Tschon M, Fini M, Giardino R, Filardo G, Dallari D, Torricelli P, Martini L, Giavaresi G, Kon E, Maltarello MC, Nicolini A, Carpi A (2011) Lights and shadows concerning platelet products for musculoskeletal regeneration. Front Biosci (Elite Ed) 3:96–107, 224CrossRefGoogle Scholar
  79. Valenzuela CD, Allori AC, Reformat DD, Sailon AM, Allen RJ, Davidson EH, Alikhani M, Bromage TG, Ricci JL, Warren SM (2013) Characterization of adipose-derived mesenchymal stem cell combinations for vascularized bone engineering. Tissue Eng Part A. doi: 10.1089/ten.TEA.2012.0323 PubMedGoogle Scholar
  80. Vittur F, Lunazzi G, Moro L, Stagni N, de Bernard B, Moretti M, Stanta G, Bacciottini F, Orlandini G, Reali N et al (1986) A possible role for polyamines in cartilage in the mechanism of calcification. Biochim Biophys Acta 881(1):38–45PubMedCrossRefGoogle Scholar
  81. Wagner EF, Karsenty G (2001) Genetic control of skeletal development. Curr Opin Genet Dev 11(5):527–532PubMedCrossRefGoogle Scholar
  82. Xiao L, Wang JY (2011) Posttranscriptional regulation of gene expression in epithelial cells by polyamines. Methods Mol Biol 720:67–79. doi: 10.1007/978-1-61779-034-8_4 PubMedCrossRefGoogle Scholar
  83. Zhao YJ, Xu CQ, Zhang WH, Zhang L, Bian SL, Huang Q, Sun HL, Li QF, Zhang YQ, Tian Y, Wang R, Yang BF, Li WM (2007) Role of polyamines in myocardial ischemia/reperfusion injury and their interactions with nitric oxide. Eur J Pharmacol 562(3):236–246. doi: 10.1016/j.ejphar.2007.01.096 PubMedCrossRefGoogle Scholar
  84. Zhao T, Goh KJ, Ng HH, Vardy LA (2012) A role for polyamine regulators in ESC self-renewal. Cell Cycle 11(24):4517–4523. doi: 10.4161/cc.22772 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  • Rosa Maria Borzì
    • 1
    • 2
  • Serena Guidotti
    • 1
    • 3
  • Manuela Minguzzi
    • 1
    • 3
  • Annalisa Facchini
    • 3
    • 4
  • Daniela Platano
    • 1
    • 3
  • Giovanni Trisolino
    • 5
  • Giuseppe Filardo
    • 6
  • Silvia Cetrullo
    • 4
  • Stefania D’Adamo
    • 4
  • Claudio Stefanelli
    • 7
  • Andrea Facchini
    • 1
    • 2
    • 3
  • Flavio Flamigni
    • 4
    Email author
  1. 1.Laboratorio di Immunoreumatologia e Rigenerazione TessutaleIstituto Ortopedico RizzoliBolognaItaly
  2. 2.Dipartimento RIT, Laboratorio RAMSESIstituto Ortopedico RizzoliBolognaItaly
  3. 3.Dipartimento di Scienze Mediche e ChirurgicheUniversità di BolognaBolognaItaly
  4. 4.Dipartimento di Scienze Biomediche e NeuromotorieUniversità di BolognaBolognaItaly
  5. 5.Chirurgia ricostruttiva articolare dell’anca e del ginocchioIstituto Ortopedico RizzoliBolognaItaly
  6. 6.Laboratorio di Biomeccanica e Innovazione Tecnologica, Clinica IIIIstituto Ortopedico RizzoliBolognaItaly
  7. 7.Dipartimento di Scienze per la Qualità della VitaUniversità di BolognaBolognaItaly

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