title: 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.
abstract: Adenosine receptors (ARs) have an important role in the regulation of inflammation and their activation is involved in the inhibition of pro-inflammatory cytokine release. The effects of pulsed electromagnetic fields (PEMFs) on inflammation have been reported and we have demonstrated that PEMFs increased A2A and A3AR density and functionality in different cell lines. Chondrocytes and osteoblasts are two key cell types in the skeletal system that play important role in cartilage and bone metabolism representing an interesting target to study the effect of PEMFs. The primary aim of the present study was to evaluate if PEMF exposure potentiated the anti-inflammatory effect of A2A and/or A3ARs in T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. Immunofluorescence, mRNA analysis and saturation binding assays revealed that PEMF exposure up-regulated A2A and A3AR expression. A2A and A3ARs were able to modulate cAMP production and cell proliferation. The activation of A2A and A3ARs resulted in the decrease of some of the most relevant pro-inflammatory cytokine release such as interleukin (IL)-6 and IL-8, following the treatment with IL-1β as an inflammatory stimuli. In human chondrocyte and osteoblast cell lines, the inhibitory effect of A2A and A3AR stimulation on the release of prostaglandin E2 (PGE2), an important lipid inflammatory mediator, was observed. In addition, in T/C-28a2 cells, the activation of A2A or A3ARs elicited an inhibition of vascular endothelial growth factor (VEGF) secretion. In hFOB 1.19 osteoblasts, PEMF exposure determined an increase of osteoprotegerin (OPG) production. The effect of the A2A or A3AR agonists in the examined cells was enhanced in the presence of PEMFs and completely blocked by using well-known selective antagonists. These results demonstrated that PEMF exposure significantly increase the anti-inflammatory effect of A2A or A3ARs suggesting their potential therapeutic use in the therapy of inflammatory bone and joint disorders.
authors.affiliation: Department of Medical Sciences, Pharmacology Unit, University of Ferrara, Ferrara, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vincenzi
authors.forename: Martina
authors.initials: M
authors.lastname: Targa
authors.forename: Carmen
authors.initials: C
authors.lastname: Corciulo
authors.forename: Stefania
authors.initials: S
authors.lastname: Gessi
authors.forename: Stefania
authors.initials: S
authors.lastname: Merighi
authors.forename: Stefania
authors.initials: S
authors.lastname: Setti
authors.forename: Ruggero
authors.initials: R
authors.lastname: Cadossi
authors.forename: Mary B
authors.initials: MB
authors.lastname: Goldring
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D058909:Adenosine A3 Receptor Agonists / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D004574:Electromagnetic Fields; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043705:Receptor, Adenosine A2A / Q000235:genetics / Q000378:metabolism*; D043684:Receptor, Adenosine A3 / Q000235:genetics / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058909:Adenosine A3 Receptor Agonists; D016328:NF-kappa B; D012333:RNA, Messenger; D043705:Receptor, Adenosine A2A; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D000242:Cyclic AMP