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Role of Adenosine Receptors in Clinical Biophysics Based on Pulsed Electromagnetic Fields

  • Katia Varani
  • Fabrizio Vincenzi
  • Matteo Cadossi
  • Stefania Setti
  • Pier Andrea Borea
  • Ruggero Cadossi
Chapter
Part of the The Receptors book series (REC, volume 34)

Abstract

Clinical biophysics studies the effects of physical agents such as the low frequency low energy pulsed electromagnetic fields (PEMFs) utilized for the treatment of different human pathologies. Much research activity has focused on the mechanisms of interaction and the metabolic pathways involved between PEMFs and the A1, A2A, A2B, and A3 adenosine receptors (ARs). In particular, PEMF exposure mediates a significant upregulation of A2A and A3ARs expressed in various cells and tissues present in both the peripheral and central nervous system involving primarily a significant reduction in some of the most interesting pro-inflammatory cytokines. Of interest is that PEMFs through the increase of ARs enhance the working efficiency of adenosine, producing a more physiological effect than the use of drugs without the side effects, desensitization, and receptor downregulation often related to the use of agonists. This observation suggests the hypothesis that PEMFs may be an interesting approach as a noninvasive treatment with a low impact on daily life mediating a significant increase on the effect of the endogenous modulator. In this chapter, the role of ARs and PEMFs and their relevance in various inflammatory diseases in both peripheral or in central nervous system disorders will be reported.

Keywords

A2A adenosine receptors Pulsed electromagnetic fields Chondrocytes Synoviocytes Osteoblasts Neuronal and microglial cells 

References

  1. Aaron RK, Boyan BD, Ciombor DM et al (2004) Stimulation of growth factor synthesis by electric and electromagnetic fields. Clin Orthop Relat Res 419:30–37CrossRefGoogle Scholar
  2. Aaron RK, Ciombor DM, Wang S et al (2006) Clinical biophysics: the promotion of skeletal repair by physical forces. Ann N Y Acad Sci 1068:513–531PubMedCrossRefPubMedCentralGoogle Scholar
  3. Adravanti P, Nicoletti S, Setti S et al (2014) Effect of pulsed electromagnetic field therapy in patients undergoing total knee arthroplasty: a randomised controlled trial. Int Orthop 38:397–403PubMedCrossRefPubMedCentralGoogle Scholar
  4. Alcantara DZ, Soliman IJS, Pobre RF et al (2017) Effects of pulsed electromagnetic fields on breast Cancer cell line MCF 7 using absorption spectroscopy. Anticancer Res 37:3453–3459PubMedPubMedCentralGoogle Scholar
  5. Arnao V, Acciarresi M, Cittadini E et al (2016) Stroke incidence, prevalence and mortality in women worldwide. Int J Stroke 11:287–301PubMedCrossRefPubMedCentralGoogle Scholar
  6. Barth A, Ponocny-Seliger E, Vana N et al (2010) Effects of extremely low frequency magnetic field exposure on cognitive functions: results of a meta- analysis. Bioelectromagnetics 31:173–179PubMedPubMedCentralGoogle Scholar
  7. Benazzo F, Cadossi M, Cavani F et al (2008a) Cartilage repair with osteochondral autografts in sheep: effect of biophysical stimulation with pulsed electromagnetic fields. J Orthop Res 26:631–642PubMedCrossRefPubMedCentralGoogle Scholar
  8. Benazzo F, Zanon G, Pederzini L et al (2008b) Effects of biophysical stimulation in patients undergoing arthroscopic reconstruction of anterior cruciate ligament: prospective, randomized and double blind study. Knee Surg Sports Traumotol Arthrosc 16:595–601CrossRefGoogle Scholar
  9. Bersani F, Marinelli F, Ognibene A et al (1997) Intramembrane protein distribution in cell cultures is affected by 50 Hz pulsed magnetic fields. Bioelectromagnetics 18:463–469PubMedCrossRefGoogle Scholar
  10. Bialy D, Wawrzynska M, Bil-Lula I et al (2015) Low frequency electromagnetic field conditioning protects against I/R injury and contractile dysfunction in the isolated rat heart. Biomed Res Int 2015:396593PubMedPubMedCentralCrossRefGoogle Scholar
  11. Borea PA, Dalpiaz A, Varani K et al (2000) Can thermodynamic measurements of receptor binding yield information on drug affinity and efficacy? Biochem Pharmacol 60:1549–1556CrossRefPubMedPubMedCentralGoogle Scholar
  12. Borea PA, Varani K, Vincenzi F et al (2015) The A3 adenosine receptor: history and perspectives. Pharmacol Rev 67:74–102PubMedCrossRefPubMedCentralGoogle Scholar
  13. Borea PA, Gessi S, Merighi S et al (2016) Adenosine as a multi-signalling guardian angel in human diseases: when, where and how does it exert its protective effects? Trends Pharmacol Sci 37:419–434CrossRefPubMedGoogle Scholar
  14. Brighton CT, Wang W, Seldes R et al (2001) Signal transduction in electrically stimulated bone cells. J Bone Joint Surg Am 83:1514–1523PubMedCrossRefPubMedCentralGoogle Scholar
  15. Cadossi R, Bersani F, Cossarizza A et al (1992) Lymphocytes and low-frequency electromagnetic fields. FASEB J 6:2667–2674PubMedCrossRefPubMedCentralGoogle Scholar
  16. Cadossi M, Buda RE, Ramponi L et al (2014) Bone marrow-derived cells and biophysical stimulation for talar osteochondral lesions: a randomized controlled study. Foot Ankle Int 35:981–987PubMedCrossRefPubMedCentralGoogle Scholar
  17. Cadossi R, Cadossi M, Setti S (2015) Physical regulation in cartilage and bone repair. In: Markov M (ed) Electromagnetic fields in biology and medicine. CRC Press, Boca Raton, Florida, USA pp 253–272Google Scholar
  18. Cadossi R, Setti S, Cadossi M et al (2017) Physical dynamics: the base for the development of biophysical treatments. In: Markov M (ed) Dosimetry in bioelectromagnetics. CRC Press, Boca Raton, Florida, USA pp 87–100Google Scholar
  19. Callaghan MH, Chang EJ, Seiser N et al (2008) Pulsed electromagnetic fields accelerate normal and diabetic wound healing by increasing endogenous FGF-2 release. Plast Reconstr Surg 121:130–141PubMedCrossRefPubMedCentralGoogle Scholar
  20. Capelli E, Torrisi F, Venturini L et al (2017) Low-frequency pulsed electromagnetic field is able to modulate miRNAs in an experimental cell model of Alzheimer’s disease. J Health Eng 2017:2530270Google Scholar
  21. Capone F, Dileone M, Profice P et al (2009) Does exposure to extremely low frequency magnetic fields produce functional changes in human brains? J Neural Transm 116:257–265PubMedCrossRefGoogle Scholar
  22. Capone F, Corbetto M, Barbato C et al (2014) An open label, one arm, dose escalation study to evaluate the safety of extremely low frequency magnetic fields in acute ischemic stroke. Austin Journal of Cerebrovascular Disease & Stroke 1:1002Google Scholar
  23. Capone F, Liberti M, Apollonio F et al (2017) An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke. Sci Rep 7:12145PubMedPubMedCentralCrossRefGoogle Scholar
  24. Chen AD, Yang DI, Lin TK et al (2011) Roles of oxidative stress, apoptosis, PGC-1α and mithochondrial biogenesis in cerebral ischemia. Int J Mol Sci 12:7199–7215PubMedPubMedCentralCrossRefGoogle Scholar
  25. Chiabrera A, Bianco B, Moggia E et al (2000) Zeeman-Stark modeling of the RF EMF interaction with ligand binding. Bioelectromagnetics 21:312–324PubMedCrossRefGoogle Scholar
  26. Collarile M, Sambri A, Lullini G et al (2018) Biophysical stimulation improves clinical results of matrix-assisted autologous chondrocyte implantation in the treatment of chondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 26:1223–1229Google Scholar
  27. Cook CM, Peek MJ (2004) Survey of the management of preterm labour in Australia and New Zealand in 2002. Aust N Z J Obstet Gynaecol 44:35–38PubMedCrossRefGoogle Scholar
  28. Cook CM, Thomas AW, Prato FS (2002) Human electrophysiological and cognitive effects of exposure to ELF magnetic and ELF modulated RF and microwave fields: a review of recent studies. Bioelectromagnetics 23:144–157PubMedCrossRefGoogle Scholar
  29. Cook CM, Saucier DM, Thomas AW et al (2006) Exposure to ELF magnetic and ELF-modulated radiofrequency fields: the time course of physiological and cognitive effects observed in recent studies (2001-2005). Bioelectromagnetics 23:144–157CrossRefGoogle Scholar
  30. Coskun O, Comlekci S (2013) The influence of pulsed electric field on hematological parameters in rat. Toxicol Ind Health 29:862–866PubMedCrossRefGoogle Scholar
  31. Crocetti S, Beyer C, Schade G et al (2013) Low intensity and frequency pulsed electromagnetic fields selectively impair breast cancer cell viability. PLoS One 8:e72944PubMedPubMedCentralCrossRefGoogle Scholar
  32. Cvetkovic D, Cosic I (2009) Alterations of human electroencephalographic activity caused by multiple extremely low frequency magnetic field exposures. Med Biol Eng Comput 47:1063–1073PubMedCrossRefGoogle Scholar
  33. Dalpiaz A, Scatturin A, Varani K et al (2000) Binding thermodynamics and intrinsic activity of adenosine A1 receptor ligands. Life Sci 67:1517–1524CrossRefPubMedGoogle Scholar
  34. de Girolamo L, Stanco D, Galliera E et al (2013) Low frequency pulsed electromagnetic field affects proliferation, tissue-specific gene expression, and cytokines release of human tendon cells. Cell Biochem Biophys 66:697–708PubMedCrossRefGoogle Scholar
  35. de Girolamo L, Viganò M, Galliera E et al (2015) In vitro functional response of human tendon cells to different dosages of low-frequency pulsed electromagnetic field. Knee Surg Sports Traumatol Arthrosc 23:3443–3453PubMedCrossRefGoogle Scholar
  36. De Mattei M, Caruso A, Pezzetti F et al (2001) Effects of pulsed electromagnetic fields on human articular chondrocyte proliferation. Connect Tissue Res 42:269–279PubMedCrossRefGoogle Scholar
  37. De Mattei M, Pasello M, Pellati A et al (2003) Effects of electromagnetic fields on proteoglycan metabolism of bovine articular cartilage explants. Connect Tissue Res 44:154–159PubMedCrossRefGoogle Scholar
  38. De Mattei M, Varani K, Masieri FF et al (2009) Adenosine analogs and electromagnetic fields inhibit prostaglandin E2 release in bovine synovial fibroblasts. Osteoarthr Cartil 17:252–262PubMedCrossRefPubMedCentralGoogle Scholar
  39. Deb P, Sharma S, Hassan KM (2010) Pathophysiologic mechanisms of acute ischemic stroke: an overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology 17:197–218PubMedCrossRefPubMedCentralGoogle Scholar
  40. Di Lazzaro V (2016) Low-frequency pulsed electromagnetic fields (ELF-MF) as treatment for acute ischemic stroke (I-NIC). clinicaltrials.gov. In: NCT02767778Google Scholar
  41. Di Lazzaro V, Capone F, Apollonio F et al (2013) A consensus panel review of central nervous system effects of the exposure to low-intensity extremely low-frequency magnetic fields. Brain Stimul 6:469–476PubMedCrossRefGoogle Scholar
  42. Ehnert S, Fentz AK, Schreiner A et al (2017) Extremely low frequency pulsed electromagnetic fields cause antioxidative defense mechanisms in human osteoblasts via induction of O2- and H2 O2 . Sci Rep 7:14544Google Scholar
  43. Ferroni L, Tocco I, De Pieri A et al (2016) Pulsed magnetic therapy increases osteogenic differentiation of mesenchymal stem cells only if they are pre-committed. Life Sci 152:44–51PubMedCrossRefGoogle Scholar
  44. Fini M, Cadossi R, Canè V et al (2002) The effect of pulsed electromagnetic fields on the osteointegration of hydroxyapatite implants in cancellous bone: a morphologic and microstructural in vivo study. J Orthop Res 20:756–763PubMedCrossRefGoogle Scholar
  45. Fini M, Giavaresi G, Carpi A et al (2005a) Effects of pulsed electromagnetic fields on articular hyaline cartilage: review of experimental and clinical studies. Biomedical Pharmacotherapeutics 59:388–394CrossRefGoogle Scholar
  46. Fini M, Giavaresi G, Torricelli P et al (2005b) Pulsed electromagnetic fields reduce knee osteoarthritic lesion progression in the aged Dunkin Hartley guinea pig. J Orthop Res 23:899–908PubMedCrossRefGoogle Scholar
  47. Fini M, Torricelli P, Giavaresi G et al (2008) Effect of pulsed electromagnetic field stimulation on knee cartilage, subchondral and epyphiseal trabecular bone of aged Dunkin Hartley guinea pigs. Biomed Pharmacother 62:709–715PubMedCrossRefGoogle Scholar
  48. Fini M, Pagani S, Giavaresi G et al (2013) Functional tissue engineering in articular cartilage repair: is there a role for electromagnetic biophysical stimulation? Tissue Eng Part B Rev 19:353–367PubMedCrossRefGoogle Scholar
  49. Fishman P, Bar-Yehuda S, Synowitz M et al (2009) Adenosine receptors and cancer. Handb Exp Pharmacol 193:399–441CrossRefGoogle Scholar
  50. Fishman P, Bar-Yehuda S, Liang BT et al (2012) Pharmacological and therapeutic effects of A3 adenosine receptor agonists. Drug Discov Today 17:359–366CrossRefPubMedGoogle Scholar
  51. Gessi S, Fogli E, Sacchetto V et al (2008) Thermodynamics of A2B adenosine receptor binding discriminates agonistic from antagonistic behavior. Biochem Pharmacol 75:562–569PubMedPubMedCentralCrossRefGoogle Scholar
  52. Gessi S, Merighi S, Fazzi D et al (2011) Adenosine receptor targeting in health and disease. Expert Opin Investig Drugs 20:1591–1609PubMedCrossRefGoogle Scholar
  53. Ghione S, Del Seppia C, Mezzasalma L et al (2004) Human head exposure to a 37 Hz electromagnetic field: effects on blood pressure, somatosensory perception, and related parameters. Bioelectromagnetics 25:167–175PubMedCrossRefGoogle Scholar
  54. Ghione S, Seppia CD, Mezzasalma L et al (2005) Effects of 50 Hz electromagnetic fields on electroencephalographic alpha activity, dental pain threshold and cardiovascular parameters in humans. Neurosci Lett 382:112–117PubMedCrossRefGoogle Scholar
  55. Giusti A, Giovale M, Ponte M et al (2013) Short-term effect of low-intensity, pulsed, electromagnetic fields on gait characteristics in older adults with low bone mineral density: a pilot randomized-controlled trial. Geriatr Gerontol Int 13:393–397PubMedCrossRefGoogle Scholar
  56. Gobbi A, Lad D, Petrera M et al (2013) Symptomatic early osteoarthritis of the knee treated with pulsed electromagnetic fields: two year follow up. Cartilage 20:1–8Google Scholar
  57. Gómez-Ochoa I, Gómez-Ochoa P, Gómez-Casal F et al (2011) Pulsed electromagnetic fields decrease proinflammatory cytokine secretion (IL-1β and TNF-α) on human fibroblast-like cell culture. Rheumatol Int 3:1283–1289CrossRefGoogle Scholar
  58. Grant G, Cadossi R, Steinberg G (1994) Protection against focal cerebral ischemia following exposure to a pulsed electromagnetic field. Bioelectromagnetics. Journal 15:205–216Google Scholar
  59. Hannemann PF, Mommers EH, Schots JP et al (2014) The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields bone growth stimulation in acute fractures: a systematic review and meta-analysis of randomized controlled trials. Arch Orthop Trauma Surg 134:1093–1106PubMedCrossRefGoogle Scholar
  60. Huegel J, Choi DS, Nuss CA et al (2018) Effects of pulsed electromagnetic field therapy at different frequencies and durations on rotator cuff tendon-to-bone healing in a rat model. J Shoulder Elbow Surg 27:553–560Google Scholar
  61. Iwasa K, Reddi AH (2018) Electromagnetic fields and tissue engineering of the joints. Tissue Eng Part B Rev 24:144–154Google Scholar
  62. Jacobson KA, Merighi S, Varani K et al (2018) A3 adenosine receptors as modulators of inflammation: from medicinal chemistry to therapy. Med Res Rev 38:1031–1072Google Scholar
  63. Jiménez-García NN, Arellanes-Robledom J, Aparicio-Bautista DI et al (2010) Anti-proliferative effect of extremely low frequency electromagnetic field on preneoplastic lesions formation in the rat liver. BMC Cancer 10:159PubMedPubMedCentralCrossRefGoogle Scholar
  64. Jing D, Zhai M, Tong S et al (2016) Pulsed electromagnetic fields promote osteogenesis and osseointegration of porous titanium implants in bone defect repair through a Wnt/β-catenin signaling-associated mechanism. Sci Rep 6:ID32045CrossRefGoogle Scholar
  65. Johnson MT, Vanscoy-Cornett A, Vesper DN et al (2001) Electromagnetic fields used clinically to improve bone healing also impact lymphocyte proliferation in vitro. Biomed Sci Instrum 37:215–220PubMedGoogle Scholar
  66. Kamel DM, Hamed NS, Abdel Raoof NA et al (2017) Pulsed magnetic field versus ultrasound in the treatment of postnatal carpal tunnel syndrome: a randomized controlled trial in the women of an Egyptian population. J Adv Res 8:45–53PubMedCrossRefGoogle Scholar
  67. Kapi E, Bozkurt M, Selcuk CT et al (2015) Comparison of effects of pulsed electromagnetic field stimulation on platelet-rich plasma and bone marrow stromal stem cell using rat zygomatic bone defect model. Ann Plast Surg 75:565–571PubMedCrossRefGoogle Scholar
  68. Kaszuba-Zwoińska J, Ćwiklińska M, Balwierz W et al (2015) Changes in cell death of peripheral blood lymphocytes isolated from children with acute lymphoblastic leukemia upon stimulation with 7 Hz, 30 mT pulsed electromagnetic field. Cell Mol Biol Lett 20:130–142PubMedCrossRefGoogle Scholar
  69. Kenakin T (2004) Principles: receptor theory in pharmacology. Trends Pharmacol Sci 25:186–192PubMedPubMedCentralCrossRefGoogle Scholar
  70. Kenakin T (2013) New concepts in pharmacological efficacy at 7TM receptors: IUPHAR review 2. Br J Pharmacol 168:554–575PubMedPubMedCentralCrossRefGoogle Scholar
  71. Kenakin T (2017) Signaling bias in drug discovery. Expert Opin Drug Discov 12:321–333PubMedCrossRefPubMedCentralGoogle Scholar
  72. Kettenmann H, Kirchoff F, Verhratsky A (2013) Microglia: new roles for the synaptic stripper. Neuron 77:10–18PubMedCrossRefPubMedCentralGoogle Scholar
  73. Khooshideh M, Latifi Rostami SS, Sheikh M et al (2017) Pulsed electromagnetic fields for postsurgical pain management in women undergoing cesarean section: a randomized, double-blind, placebo-controlled trial. Clin J Pain 33:142–147PubMedCrossRefPubMedCentralGoogle Scholar
  74. Legros A, Beuter A (2005) Effect of a low intensity magnetic field on human motor behavior. Bioelectromagnetics 26:657–669PubMedCrossRefPubMedCentralGoogle Scholar
  75. Legros A, Beuter A (2006) Individual subject sensitivity to extremely low frequency magnetic field. Neurotoxicology 27:534–546PubMedCrossRefPubMedCentralGoogle Scholar
  76. Li RL, Huang JJ, Shi YQ et al (2015) Pulsed electromagnetic field improves postnatal neovascularization in response to hindlimb ischemia. Am J Transl Res 7:430–444PubMedPubMedCentralGoogle Scholar
  77. Lim S, Kim SC, Kim JY (2015) Protective effect of 10-Hz, 1-mT electromagnetic field exposure against hypoxia/reoxygenation injury in HK-2 cells. Biomed Environ Sci 28:231–234PubMedGoogle Scholar
  78. Lotz MK, Kraus VB (2010) New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options. Arthritis Res Ther 12:211PubMedPubMedCentralCrossRefGoogle Scholar
  79. Ma F, Li W, Li X et al (2016) Novel protective effects of pulsed electromagnetic field ischemia/reperfusion injury rats. Biosci Rep 36(6):pii: e00420CrossRefGoogle Scholar
  80. Marcheggiani Muccioli GM, Grassi A, Setti S et al (2013) Conservative treatment of spontaneous osteonecrosis of the knee in the early stage: pulsed electromagnetic fields therapy. Eur J Radiol 82:530–537PubMedCrossRefPubMedCentralGoogle Scholar
  81. Massari L, Benazzo F, De Mattei M et al (2007) CRES study group. Effects of electrical physical stimuli on articular cartilage. J Bone Joint Surg Am 89:152–161PubMedGoogle Scholar
  82. Massari L, Osti F, Lorusso V et al (2015) Biophysical stimulation and the periprosthetic bone: is there a rationale in the use of pulsed electromagnetic fields after a hip or knee implant? Journal of Biological Regulator and Homeostatic Agents 29:1013–1015Google Scholar
  83. Merighi S, Varani K, Gessi S et al (2002) Binding thermodynamics at the human A3 adenosine receptor. Biochem Pharmacol 63:157–161CrossRefPubMedGoogle Scholar
  84. Moretti B, Notarnicola A, Moretti L et al (2012) I-ONE therapy in patients undergoing total knee arthroplasty: a prospective, randomized and controlled study. BMC Musculoskelet Disord 13:88PubMedPubMedCentralCrossRefGoogle Scholar
  85. Ongaro A, Pellati A, Masieri FF et al (2011) Chondroprotective effects of pulsed electromagnetic fields on human cartilage explants. Bioelectromagnetics 32:543–551PubMedCrossRefGoogle Scholar
  86. Ongaro A, Varani K, Masieri FF et al (2012) Electromagnetic fields (EMFs) and adenosine receptors modulate prostaglandin E(2) and cytokine release in human osteoarthritic synovial fibroblasts. J Cell Physiol 227:2461–2469PubMedCrossRefGoogle Scholar
  87. Pagani S, Veronesi F, Aldini NN et al (2017) Complex regional pain syndrome type I, a debilitating and poorly understood syndrome. Possible role for pulsed electromagnetic fields: a narrative review. Pain Physician 20:E807–E822PubMedGoogle Scholar
  88. Pena-Philippides JC, Yang Y, Bragina O et al (2014) Effect of pulsed electromagnetic field (PEMF) on infarct size and inflammation after cerebral ischemia in mice. Transl Stroke Res 5:491–500PubMedCrossRefGoogle Scholar
  89. Prato FS, Thomas AW, Cook CM (2001) Human standing balance is affected by exposure to pulsed ELF magnetic fields: light intensity-dependent effects. Neuroreport 12:1501–1505PubMedCrossRefGoogle Scholar
  90. Rohde C, Chiang A, Adipoju O et al (2010) Effects of pulsed electromagnetic fields on interleukin-1 beta and postoperative pain: a double-blind, placebo-controlled, pilot study in breast reduction patients. Plast Reconstr Surg 125:1620–1629PubMedCrossRefGoogle Scholar
  91. Servodio Iammarrone C, Cadossi M, Sambri A et al (2016) Is there a role of pulsed electromagnetic fields in management of patellofemoral pain syndrome? Randomized controlled study at one year follow-up. Bioelectromagnetics 37:81–88PubMedCrossRefGoogle Scholar
  92. Sollazzo V, Palmieri A, Pezzetti F et al (2010) Effects of pulsed electromagnetic fields on human osteoblast like cells (MG-63): a pilot study. Clin Orthop Relat Res 468:2260–2277PubMedPubMedCentralCrossRefGoogle Scholar
  93. Stevens P (2007) Affective response to a 5 microT ELF magnetic field-induced physiological changes. Bioelectromagnetics 28:109–114PubMedCrossRefGoogle Scholar
  94. Sun J, Kwan RL, Zheng Y et al (2016) Effects of pulsed electromagnetic fields on peripheral blood circulation in people with diabetes: a randomized controlled trial. Bioelectromagnetics 37:290–297PubMedCrossRefGoogle Scholar
  95. Thomas AW, Drost DJ, Prato FS (2001) Huuman subjects exposed to a specific pulsed (200 microT) magnetic field: effects on normal standing balance. Neurosci Lett 297:121–124PubMedCrossRefGoogle Scholar
  96. Tschon M, Veronesi F, Contartese D et al (2018) Effects of pulsed electromagnetic fields and platelet rich plasma in preventing osteoclastogenesis in an in vitro model of osteolysis. J Cell Physiol 233:2645–2656PubMedCrossRefGoogle Scholar
  97. Vadalà M, Vallelunga A, Palmieri L et al (2015) Mechanisms and therapeutic applications of electromagnetic therapy in Parkinson’s disease. Behav Brain Funct 11:26PubMedPubMedCentralCrossRefGoogle Scholar
  98. van Belkum SM, Bosker FJ, Kortekaas R et al (2016) Treatment of depression with low-strength transcranial pulsed electromagnetic fields: a mechanistic point of view. Prog Neuro-Psychopharmacol Biol Psychiatry 71:137–143CrossRefGoogle Scholar
  99. Varani K, Gessi S, Dalpiaz A et al (1997) Characterization of A2A adenosine receptors in human lymphocyte membranes by [3H]-SCH 58261 binding. Br J Pharmacol 122:386–392PubMedPubMedCentralCrossRefGoogle Scholar
  100. Varani K, Gessi S, Dionisotti S et al (1998) [3H]-SCH 58261 labelling of functional A2A adenosine receptors in human neutrophil membranes. Br J Pharmacol 123:1723–1731PubMedPubMedCentralCrossRefGoogle Scholar
  101. Varani K, Gessi S, Merighi S et al (2002) Effect of low frequency electromagnetic fields on A2A adenosine receptors in human neutrophils. Br J Pharmacol 136:57–66PubMedPubMedCentralCrossRefGoogle Scholar
  102. Varani K, Gessi S, Merighi S et al (2003) Alteration of A3 adenosine receptors in human neutrophils and low frequency electromagnetic fields. Biochem Pharmacol 66:1897–1906PubMedCrossRefGoogle Scholar
  103. Varani K, De Mattei M, Vincenzi F et al (2008) Characterization of adenosine receptors in bovine chondrocytes and fibroblast-like synoviocytes exposed to low frequency low energy pulsed electromagnetic fields. Osteoarthr Cartil 16:292–304CrossRefPubMedGoogle Scholar
  104. Varani K, Vincenzi F, Tosi A et al (2010) Expression and functional role of adenosine receptors in regulating inflammatory responses in human synoviocytes. Br J Pharmacol 160:101–115PubMedPubMedCentralCrossRefGoogle Scholar
  105. Varani K, Maniero S, Vincenzi F et al (2011) A3 receptors are overexpressed in pleura from patients with mesothelioma and reduce cell growth via Akt/nuclear factor-κB pathway. Am J Respir Crit Care Med 183(4):522–530PubMedCrossRefGoogle Scholar
  106. Varani K, Vincenzi F, Targa M et al (2012) Effect of pulsed electromagnetic field exposure on adenosine receptors in rat brain. Bioelectromagnetics 33:279–287PubMedCrossRefGoogle Scholar
  107. Varani K, Vincenzi F, Targa M et al (2013) The stimulation of A3 adenosine receptors reduces bone-residing breast cancer in a rat preclinical model. Eur J Cancer 49:482–491PubMedCrossRefGoogle Scholar
  108. Varani K, Vincenzi F, Merighi S et al (2017a) Biochemical and pharmacological role of A1 adenosine receptors and their modulation as novel therapeutic strategy. Adv Exp Med Biol 1051:193–232PubMedCrossRefGoogle Scholar
  109. Varani K, Vincenzi F, Ravani A et al (2017b) Adenosine receptors as a biological pathway for the anti-inflammatory and beneficial effects of low frequency low energy pulsed electromagnetic fields. Mediat Inflamm 2017:ID 27440963CrossRefGoogle Scholar
  110. Veronesi F, Torricelli P, Giavaresi G et al (2014) In vivo effect of two different pulsed electromagnetic field frequencies on osteoarthritis. Journal of Orthopaedic Reseach 32:677–685CrossRefGoogle Scholar
  111. Veronesi F, Cadossi M, Giavaresi G et al (2015) Pulsed electromagnetic fields combined with a collagenous scaffold and bone marrow concentrate enhance osteochondral regeneration: an in vivo study. BMC Musculoskelet Disorders 16:233CrossRefGoogle Scholar
  112. Vincenzi F, Targa M, Corciulo C et al (2012) The anti-tumor effect of A3 adenosine receptors is potentiated by pulsed electromagnetic fields in cultured neural cancer cells. PLoS One 7:ID e39317CrossRefGoogle Scholar
  113. Vincenzi F, Targa M, Corciulo C et al (2013) Pulsed electromagnetic fields increased the anti-inflammatory effect of A2A and A3 adenosine receptors in human T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. PLoS One 8:e65561PubMedPubMedCentralCrossRefGoogle Scholar
  114. Vincenzi F, Ravani A, Pasquini S et al (2017) Pulsed electromagnetic field exposure reduces hypoxia and inflammation damage in neuron-like and microglial cell. J Cell Physiol 232:1200–1208PubMedCrossRefPubMedCentralGoogle Scholar
  115. Wang Q, Tang XN, Yenari MA (2007) The inflammatory response in stroke. J Neuroimmunol 184:53–68PubMedCrossRefGoogle Scholar
  116. Xie YX, Shi WG, Zhou J et al (2016) Pulsed electromagnetic fields stimulate osteogenic differentiation and maturation of osteoblasts by upregulating the expression of BMPRII localized at the base of primary cilium. Bone 93:22–32PubMedCrossRefPubMedCentralGoogle Scholar
  117. Xing C, Arai K, Lo EH et al (2012) Pathophysiologic cascades in ischemic stroke. Int J Stroke 7(5):378–385PubMedPubMedCentralCrossRefGoogle Scholar
  118. Yang X, He H, Gao Q et al (2018) Pulsed electromagnetic field improves subchondral bone microstructure in knee osteoarthritis rats through a Wnt/β -catenin signaling-associated mechanism. Bioelectromagnetics 39:89–97Google Scholar
  119. Zhai Y, Jing D, Tong S et al (2016) Pulsed electromagnetic fields promote in vitro osteoblastogenesis through a Wnt/β-catenin signaling-associated mechanism. Bioelectromagnetics. https://doi.org/10.1002/bem.21961
  120. Zhu S, He H, Zhang C et al (2017) Effects of pulsed electromagnetic fields on postmenopausal osteoporosis. Bioelectromagnetics 38:406–424PubMedCrossRefGoogle Scholar
  121. Zorzi C, Dall’oca C, Cadossi R et al (2007) Effects of pulsed electromagnetic fields on patients’ recovery after arthroscopic surgery: prospective, randomized and double-blind study. Knee Surgery Sports Traumatology Arthroscopy 15:830–834CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • Katia Varani
    • 1
  • Fabrizio Vincenzi
    • 1
  • Matteo Cadossi
    • 2
  • Stefania Setti
    • 2
  • Pier Andrea Borea
    • 1
  • Ruggero Cadossi
    • 2
  1. 1.Department of Medical SciencesUniversity of FerraraFerraraItaly
  2. 2.Igea, Biophysic LaboratoriesCarpiItaly

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