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Mediators of Inflammation
Volume 2017 (2017), Article ID 2740963, 11 pages
https://doi.org/10.1155/2017/2740963
Review Article

Adenosine Receptors as a Biological Pathway for the Anti-Inflammatory and Beneficial Effects of Low Frequency Low Energy Pulsed Electromagnetic Fields

1Department of Medical Sciences, Pharmacology Unit, University of Ferrara, Via Fossato di Mortara 17-19, 44121 Ferrara, Italy
2IGEA Biophysics Laboratory, Carpi, Italy

Correspondence should be addressed to Katia Varani; ti.efinu@krv

Received 20 October 2016; Accepted 12 January 2017; Published 1 February 2017

Academic Editor: Elaine Hatanaka

Copyright © 2017 Katia Varani et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. A. Borea, S. Gessi, S. Merighi, and K. Varani, “Adenosine as a multi-signalling guardian angel in human diseases: when, where and how does it exert its protective effects?” Trends in Pharmacological Sciences, vol. 37, no. 6, pp. 419–434, 2016. View at Publisher · View at Google Scholar · View at Scopus
  2. P. A. Borea, K. Varani, F. Vincenzi et al., “The A3 adenosine receptor: history and perspectives,” Pharmacological Reviews, vol. 67, no. 1, pp. 74–102, 2015. View at Publisher · View at Google Scholar · View at Scopus
  3. S. Gessi, S. Merighi, D. Fazzi, A. Stefanelli, K. Varani, and P. A. Borea, “Adenosine receptor targeting in health and disease,” Expert Opinion on Investigational Drugs, vol. 20, no. 12, pp. 1591–1609, 2011. View at Publisher · View at Google Scholar · View at Scopus
  4. D. Preti, P. G. Baraldi, A. R. Moorman, P. A. Borea, and K. Varani, “History and perspectives of A2A adenosine receptor antagonists as potential therapeutic agents,” Medicinal Research Reviews, vol. 35, no. 4, pp. 790–848, 2015. View at Publisher · View at Google Scholar · View at Scopus
  5. S. Gessi, S. Merighi, V. Sacchetto, C. Simioni, and P. A. Borea, “Adenosine receptors and cancer,” Biochimica et Biophysica Acta—Biomembranes, vol. 1808, no. 5, pp. 1400–1412, 2011. View at Publisher · View at Google Scholar · View at Scopus
  6. K. Varani, M. Padovan, M. Govoni, F. Vincenzi, F. Trotta, and P. A. Borea, “The role of adenosine receptors in rheumatoid arthritis,” Autoimmunity Reviews, vol. 10, no. 2, pp. 61–64, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. D. Correa and S. A. Lietman, “Articular cartilage repair: current needs, methods and research directions,” Seminars in Cell & Developmental Biology, vol. 16, no. 30, pp. 208–217, 2016. View at Google Scholar
  8. M. Rahmati, A. Mobasheri, and M. Mozafari, “Inflammatory mediators in osteoarthritis: a critical review of the state-of-the-art, current prospects, and future challenges,” Bone, vol. 85, pp. 81–90, 2016. View at Publisher · View at Google Scholar
  9. M. S. Chimenti, P. Triggianese, P. Conigliaro, E. Candi, G. Melino, and R. Perricone, “The interplay between inflammation and metabolism in rheumatoid arthritis,” Cell Death & Disease, vol. 6, Article ID e1887, 2015. View at Publisher · View at Google Scholar · View at Scopus
  10. K. Varani, M. De Mattei, F. Vincenzi et al., “Characterization of adenosine receptors in bovine chondrocytes and fibroblast-like synoviocytes exposed to low frequency low energy pulsed electromagnetic fields,” Osteoarthritis and Cartilage, vol. 16, no. 3, pp. 292–304, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. K. Varani, F. Vincenzi, A. Tosi et al., “Expression and functional role of adenosine receptors in regulating inflammatory responses in human synoviocytes,” British Journal of Pharmacology, vol. 160, no. 1, pp. 101–115, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. F. Vincenzi, M. Targa, C. Corciulo et al., “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, vol. 8, no. 5, Article ID e65561, 2013. View at Publisher · View at Google Scholar · View at Scopus
  13. S. H. Carroll, N. A. Wigner, N. Kulkarni, H. Johnston-Cox, L. C. Gerstenfeld, and K. Ravid, “A2B adenosine receptor promotes mesenchymal stem cell differentiation to osteoblasts and bone formation in vivo,” Journal of Biological Chemistry, vol. 287, no. 19, pp. 15718–15727, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. M. Takedachi, H. Oohara, B. J. Smith et al., “CD73-generated adenosine promotes osteoblast differentiation,” Journal of Cellular Physiology, vol. 227, no. 6, pp. 2622–2631, 2012. View at Publisher · View at Google Scholar · View at Scopus
  15. W. He and B. Cronstein, “The roles of adenosine and adenosine receptors in bone remodeling,” Frontiers in Bioscience, vol. 3, no. 3, pp. 888–895, 2011. View at Google Scholar · View at Scopus
  16. F. M. Kara, S. B. Doty, A. Boskey et al., “Adenosine A1 receptors regulate bone resorption in mice: adenosine A1 receptor blockade or deletion increases bone density and prevents ovariectomy-induced bone loss in adenosine A1 receptor-knockout mice,” Arthritis & Rheumatism, vol. 62, no. 2, pp. 534–541, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Cadossi and S. Setti, “The role of physical forces in the management of bone and cartilage diseases and bone consolidation,” Aging Clinical and Experimental Research, vol. 23, no. 2, pp. 49–51, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. M. Fini, S. Pagani, G. Giavaresi et al., “Functional tissue engineering in articular cartilage repair: is there a role for electromagnetic biophysical stimulation?” Tissue Engineering Part B: Reviews, vol. 19, no. 4, pp. 353–367, 2013. View at Publisher · View at Google Scholar · View at Scopus
  19. V. Di Lazzaro, F. Capone, F. Apollonio et al., “A consensus panel review of central nervous system effects of the exposure to low-intensity extremely low-frequency magnetic fields,” Brain Stimulation, vol. 6, no. 4, pp. 469–476, 2013. View at Publisher · View at Google Scholar · View at Scopus
  20. G. Grant, R. Cadossi, and G. Steinberg, “Protection against focal cerebral ischemia following exposure to a pulsed electromagnetic field,” Bioelectromagnetics, vol. 15, no. 3, pp. 205–216, 1994. View at Publisher · View at Google Scholar · View at Scopus
  21. B. Chalidis, N. Sachinis, A. Assiotis, and G. Maccauro, “Stimulation of bone formation and fracture healing with pulsed electromagnetic fields: biologic responses and clinical implications,” International Journal of Immunopathology and Pharmacology, vol. 24, no. 1, supplement 2, pp. 17–20, 2011. View at Google Scholar · View at Scopus
  22. H.-Y. Lin and Y.-J. Lin, “In vitro effects of low frequency electromagnetic fields on osteoblast proliferation and maturation in an inflammatory environment,” Bioelectromagnetics, vol. 32, no. 7, pp. 552–560, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. V. Sollazzo, A. Palmieri, F. Pezzetti, L. Massari, and F. Carinci, “Effects of pulsed electromagnetic fields on human osteoblastlike cells (MG-63): A Pilot Study,” Clinical Orthopaedics and Related Research, vol. 468, no. 8, pp. 2260–2277, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. M. De Mattei, M. Pasello, A. Pellati et al., “Effects of electromagnetic fields on proteoglycan metabolism of bovine articular cartilage explants,” Connective Tissue Research, vol. 44, no. 3-4, pp. 154–159, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. A. Ongaro, K. Varani, F. F. Masieri et al., “Electromagnetic fields (EMFs) and adenosine receptors modulate prostaglandin E2 and cytokine release in human osteoarthritic synovial fibroblasts,” Journal of Cellular Physiology, vol. 227, no. 6, pp. 2461–2469, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. F. Veronesi, M. Cadossi, G. Giavaresi et al., “Pulsed electromagnetic fields combined with a collagenous scaffold and bone marrow concentrate enhance osteochondral regeneration: an in vivo study,” BMC Musculoskeletal Disorders, vol. 16, no. 1, article 233, 2015. View at Publisher · View at Google Scholar · View at Scopus
  27. C. Zorzi, C. Dall'Oca, R. Cadossi, and S. Setti, “Effects of pulsed electromagnetic fields on patients' recovery after arthroscopic surgery: prospective, randomized and double-blind study,” Knee Surgery, Sports Traumatology, Arthroscopy, vol. 15, no. 7, pp. 830–834, 2007. View at Publisher · View at Google Scholar · View at Scopus
  28. P. F. W. Hannemann, E. H. H. Mommers, J. P. M. Schots, P. R. G. Brink, and M. Poeze, “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,” Archives of Orthopaedic and Trauma Surgery, vol. 134, no. 8, pp. 1093–1106, 2014. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Crocetti, C. Beyer, G. Schade, M. Egli, J. Fröhlich, and A. Franco-Obregón, “Low intensity and frequency pulsed electromagnetic fields selectively impair breast cancer cell viability,” PLoS ONE, vol. 8, no. 9, Article ID e72944, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. M. N. Jiménez-García, J. Arellanes-Robledo, D. I. Aparicio-Bautista, M. T. Rodríguez-Segura, S. Villa-Treviño, and J. J. Godina-Nava, “Anti-proliferative effect of extremely low frequency electromagnetic field on preneoplastic lesions formation in the rat liver,” BMC Cancer, vol. 10, article no. 159, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. F. Vincenzi, M. Targa, C. Corciulo et al., “The anti-tumor effect of A3 adenosine receptors is potentiated by pulsed electromagnetic fields in cultured neural cancer cells,” PLoS ONE, vol. 7, no. 6, Article ID e39317, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Rohde, A. Chiang, O. Adipoju, D. Casper, and A. A. Pilla, “Effects of pulsed electromagnetic fields on interleukin-1β and postoperative pain: a double-blind, placebo-controlled, pilot study in breast reduction patients,” Plastic and Reconstructive Surgery, vol. 125, no. 6, pp. 1620–1629, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Lim, S.-C. Kim, and J. Y. O. Kim, “Protective effect of 10-Hz, 1-mT electromagnetic field exposure against hypoxia/reoxygenation injury in HK-2 cells,” Biomedical and Environmental Sciences, vol. 28, no. 3, pp. 231–234, 2015. View at Publisher · View at Google Scholar · View at Scopus
  34. D. Bialy, M. Wawrzynska, I. Bil-Lula et al., “Low frequency electromagnetic field conditioning protects against I/R injury and contractile dysfunction in the isolated rat heart,” BioMed Research International, vol. 2015, Article ID 396593, 7 pages, 2015. View at Publisher · View at Google Scholar · View at Scopus
  35. A. Albertini, P. Zucchini, G. Noera, R. Cadossi, C. Pace Napoleone, and A. Pierangeli, “Protective effect of low frequency low energy pulsing electromagnetic fields on acute experimental myocardial infarcts in rats,” Bioelectromagnetics, vol. 20, no. 6, pp. 372–377, 1999. View at Publisher · View at Google Scholar · View at Scopus
  36. J. C. Pena-Philippides, Y. Yang, O. Bragina, S. Hagberg, E. Nemoto, and T. Roitbak, “Effect of Pulsed Electromagnetic Field (PEMF) on Infarct Size and Inflammation After Cerebral Ischemia in Mice,” Translational Stroke Research, vol. 5, no. 4, pp. 491–500, 2014. View at Publisher · View at Google Scholar · View at Scopus
  37. F. Vincenzi, A. Ravani, S. Pasquini et al., “Pulsed electromagnetic field exposure reduces hypoxia and inflammation damage in neuron-like and microglial cells,” Journal of Cellular Physiology, vol. 232, no. 5, pp. 1200–1208, 2017. View at Publisher · View at Google Scholar
  38. M. De Mattei, K. Varani, F. F. Masieri et al., “Adenosine analogs and electromagnetic fields inhibit prostaglandin E2 release in bovine synovial fibroblasts,” Osteoarthritis and Cartilage, vol. 17, no. 2, pp. 252–262, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. A. Ongaro, A. Pellati, F. F. Masieri et al., “Chondroprotective effects of pulsed electromagnetic fields on human cartilage explants,” Bioelectromagnetics, vol. 32, no. 7, pp. 543–551, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. K. Varani, F. Vincenzi, M. Targa et al., “Effect of pulsed electromagnetic field exposure on adenosine receptors in rat brain,” Bioelectromagnetics, vol. 33, no. 4, pp. 279–287, 2012. View at Publisher · View at Google Scholar · View at Scopus
  41. R. Cadossi, F. Bersani, A. Cossarizza et al., “Lymphocytes and low-frequency electromagnetic fields,” FASEB Journal, vol. 6, no. 9, pp. 2667–2674, 1992. View at Google Scholar · View at Scopus
  42. K. Varani, S. Gessi, A. Dalpiaz, E. Ongini, and P. A. Borea, “Characterization of A2A adenosine receptors in human lymphocyte membranes by [3H]-SCH 58261 binding,” British Journal of Pharmacology, vol. 122, no. 2, pp. 386–392, 1997. View at Publisher · View at Google Scholar · View at Scopus
  43. K. Varani, S. Gessi, S. Dionisotti, E. Ongini, and P. A. Borea, “[3H]-SCH 58261 labelling of functional A2A adenosine receptors in human neutrophil membranes,” British Journal of Pharmacology, vol. 123, no. 8, pp. 1723–1731, 1998. View at Publisher · View at Google Scholar · View at Scopus
  44. F. Bersani, F. Marinelli, A. Ognibene et al., “Intramembrane protein distribution in cell cultures is affected by 50 Hz pulsed magnetic fields,” Bioelectromagnetics, vol. 18, no. 7, pp. 463–469, 1997. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Chiabrera, B. Bianco, E. Moggia, and J. J. Kaufman, “Zeeman-Stark modeling of the RF EMF interaction with ligand binding,” Bioelectromagnetics, vol. 21, no. 4, pp. 312–324, 2000. View at Publisher · View at Google Scholar
  46. K. Varani, S. Gessi, S. Merighi et al., “Effect of low frequency electromagnetic fields on A2A adenosine receptors in human neutrophils,” British Journal of Pharmacology, vol. 136, no. 1, pp. 57–66, 2002. View at Publisher · View at Google Scholar · View at Scopus
  47. K. Varani, S. Gessi, S. Merighi et al., “Alteration of A3 adenosine receptors in human neutrophils and low frequency electromagnetic fields,” Biochemical Pharmacology, vol. 66, no. 10, pp. 1897–1906, 2003. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Dalpiaz, A. Scatturin, K. Varani, R. Pecoraro, B. Pavan, and P. A. Borea, “Binding thermodynamics and intrinsic activity of adenosine A1 receptor ligands,” Life Sciences, vol. 67, no. 12, pp. 1517–1524, 2000. View at Publisher · View at Google Scholar · View at Scopus
  49. P. A. Borea, A. Dalpiaz, K. Varani, P. Gilli, and G. Gilli, “Can thermodynamic measurements of receptor binding yield information on drug affinity and efficacy?” Biochemical Pharmacology, vol. 60, no. 11, pp. 1549–1556, 2000. View at Publisher · View at Google Scholar · View at Scopus
  50. S. Merighi, K. Varani, S. Gessi et al., “Binding thermodynamics at the human A3 adenosine receptor,” Biochemical Pharmacology, vol. 63, no. 2, pp. 157–161, 2002. View at Publisher · View at Google Scholar · View at Scopus
  51. S. Gessi, E. Fogli, V. Sacchetto et al., “Thermodynamics of A2B adenosine receptor binding discriminates agonistic from antagonistic behaviour,” Biochemical Pharmacology, vol. 75, no. 2, pp. 562–569, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. J. Sun, R. L.-C. Kwan, Y. Zheng, and G. L.-Y. Cheing, “Effects of pulsed electromagnetic fields on peripheral blood circulation in people with diabetes: a randomized controlled trial,” Bioelectromagnetics, vol. 37, no. 5, pp. 290–297, 2016. View at Publisher · View at Google Scholar · View at Scopus
  53. M. J. Callaghan, E. I. Chang, N. Seiser et al., “Pulsed electromagnetic fields accelerate normal and diabetic wound healing by increasing endogenous FGF-2 release,” Plastic and Reconstructive Surgery, vol. 121, no. 1, pp. 130–141, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. E. Kapi, M. Bozkurt, C. T. Selcuk et al., “Comparison of effects of pulsed electromagnetic field stimulation on platelet-rich plasma and bone marrow stromal stem cell using rat zygomatic bone defect model,” Annals of Plastic Surgery, vol. 75, no. 5, pp. 565–571, 2015. View at Publisher · View at Google Scholar · View at Scopus
  55. I. Gómez-Ochoa, P. Gómez-Ochoa, F. Gómez-Casal, E. Cativiela, and L. Larrad-Mur, “Pulsed electromagnetic fields decrease proinflammatory cytokine secretion (IL-1β and TNF-α) on human fibroblast-like cell culture,” Rheumatology International, vol. 31, no. 10, pp. 1283–1289, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. M. T. Johnson, A. Vanscoy-Cornett, D. N. Vesper et al., “Electromagnetic fields used clinically to improve bone healing also impact lymphocyte proliferation in vitro,” Biomedical Sciences Instrumentation, vol. 37, pp. 215–220, 2001. View at Google Scholar · View at Scopus
  57. M. Fini, G. Giavaresi, P. Torricelli et al., “Pulsed electromagnetic fields reduce knee osteoarthritic lesion progression in the aged Dunkin Hartley guinea pig,” Journal of Orthopaedic Research, vol. 23, no. 4, pp. 899–908, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. M. Fini, G. Giavaresi, A. Carpi, A. Nicolini, S. Setti, and R. Giardino, “Effects of pulsed electromagnetic fields on articular hyaline cartilage: review of experimental and clinical studies,” Biomedicine and Pharmacotherapy, vol. 59, no. 7, pp. 388–394, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. Y.-F. Xie, W.-G. Shi, J. Zhou et al., “Pulsed electromagnetic fields stimulate osteogenic differentiation and maturation of osteoblasts by upregulating the expression of BMPRII localized at the base of primary cilium,” Bone, vol. 93, pp. 22–32, 2016. View at Publisher · View at Google Scholar
  60. D. Jing, M. Zhai, S. Tong et al., “Pulsed electromagnetic fields promote osteogenesis and osseointegration of porous titanium implants in bone defect repair through a Wnt/β-catenin signaling-associated mechanism,” Scientific Reports, vol. 6, Article ID 32045, 2016. View at Publisher · View at Google Scholar · View at Scopus
  61. L. Ferroni, I. Tocco, A. De Pieri et al., “Pulsed magnetic therapy increases osteogenic differentiation of mesenchymal stem cells only if they are pre-committed,” Life Sciences, vol. 152, pp. 44–51, 2016. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Zhai, D. Jing, S. Tong et al., “Pulsed electromagnetic fields promote in vitro osteoblastogenesis through a Wnt/β-catenin signaling-associated mechanism,” Bioelectromagnetics, vol. 37, no. 3, pp. 152–162, 2016. View at Publisher · View at Google Scholar · View at Scopus
  63. F. Veronesi, P. Torricelli, G. Giavaresi et al., “In vivo effect of two different pulsed electromagnetic field frequencies on osteoarthritis,” Journal of Orthopaedic Research, vol. 32, no. 5, pp. 677–685, 2014. View at Publisher · View at Google Scholar · View at Scopus
  64. L. Massari, R. Osti, V. Lorusso, S. Setti, and G. Caruso, “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 Regulators and Homeostatic Agents, vol. 29, no. 4, pp. 1013–1015, 2015. View at Google Scholar · View at Scopus
  65. M. Vadalà, A. Vallelunga, L. Palmieri, B. Palmieri, J. C. Morales-Medina, and T. Iannitti, “Mechanisms and therapeutic applications of electromagnetic therapy in Parkinson's disease,” Behavioral and Brain Functions, vol. 11, no. 1, article 26, 2015. View at Publisher · View at Google Scholar · View at Scopus
  66. S. van Belkum, F. Bosker, R. Kortekaas, D. Beersma, and R. Schoevers, “Treatment of depression with low-strength transcranial pulsed electromagnetic fields: a mechanistic point of view,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 71, pp. 137–143, 2016. View at Publisher · View at Google Scholar
  67. K. Varani, S. Maniero, F. Vincenzi et al., “A3 receptors are overexpressed in pleura from patients with mesothelioma and reduce cell growth via Akt/nuclear factor-κB pathway,” American Journal of Respiratory and Critical Care Medicine, vol. 183, no. 4, pp. 522–530, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. K. Varani, F. Vincenzi, M. Targa et al., “The stimulation of A3 adenosine receptors reduces bone-residing breast cancer in a rat preclinical model,” European Journal of Cancer, vol. 49, no. 2, pp. 482–491, 2013. View at Publisher · View at Google Scholar · View at Scopus
  69. P. Fishman, S. Bar-Yehuda, M. Synowitz et al., “Adenosine receptors and cancer,” Handbook of Experimental Pharmacology, vol. 193, pp. 399–441, 2009. View at Publisher · View at Google Scholar · View at Scopus
  70. S. Gessi, S. Merighi, K. Varani, E. Leung, S. Mac Lennan, and P. A. Borea, “The A3 adenosine receptor: an enigmatic player in cell biology,” Pharmacology & Therapeutics, vol. 117, no. 1, pp. 123–140, 2008. View at Publisher · View at Google Scholar · View at Scopus
  71. P. Fishman, S. Bar-Yehuda, B. T. Liang, and K. A. Jacobson, “Pharmacological and therapeutic effects of A3 adenosine receptor agonists,” Drug Discovery Today, vol. 17, no. 7-8, pp. 359–366, 2012. View at Publisher · View at Google Scholar · View at Scopus
  72. F. Capone, M. Corbetto, C. Barbato et al., “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, vol. 1, no. 1, p. 1002, 2014. View at Google Scholar
  73. V. Di Lazzaro, “Low-frequency pulsed electromagnetic fields (ELF-MF) as treatment for acute ischemic stroke (I-NIC),” clinicaltrials.gov, NCT02767778, 2016.
  74. S. Morello, R. Sorrentino, A. Porta et al., “Cl-IB-MECA enhances TRAIL-induced apoptosis via the modulation of NF-κB signalling pathway in thyroid cancer cells,” Journal of Cellular Physiology, vol. 221, no. 2, pp. 378–386, 2009. View at Publisher · View at Google Scholar · View at Scopus
  75. R. K. Aaron, B. D. Boyan, D. M. Ciombor, Z. Schwartz, and B. J. Simon, “Stimulation of growth factor synthesis by electric and electromagnetic fields,” Clinical Orthopaedics and Related Research, no. 419, pp. 30–37, 2004. View at Google Scholar · View at Scopus
  76. M. K. Lotz, “New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options,” Arthritis Research and Therapy, vol. 12, no. 3, article 211, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. M. De Mattei, A. Caruso, F. Pezzetti et al., “Effects of pulsed electromagnetic fields on human articular chondrocyte proliferation,” Connective Tissue Research, vol. 42, no. 4, pp. 269–279, 2001. View at Publisher · View at Google Scholar · View at Scopus
  78. B. Moretti, A. Notarnicola, L. Moretti et al., “I-ONE therapy in patients undergoing total knee arthroplasty: a prospective, randomized and controlled study,” BMC Musculoskeletal Disorders, vol. 13, article no. 88, 2012. View at Publisher · View at Google Scholar · View at Scopus
  79. T. Kenakin, “Principles: receptor theory in pharmacology,” Trends in Pharmacological Sciences, vol. 25, no. 4, pp. 186–192, 2004. View at Publisher · View at Google Scholar · View at Scopus
  80. T. Kenakin, “New concepts in pharmacological efficacy at 7TM receptors: IUPHAR Review 2,” British Journal of Pharmacology, vol. 168, no. 3, pp. 554–575, 2013. View at Publisher · View at Google Scholar · View at Scopus