Pulsed Electromagnetic Fields Increased the Anti-Inflammatory Effect of A(2A) and A(3) Adenosine Receptors in Human T/C-28a2 Chondrocytes and hFOB 1.19 Osteoblasts

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 A(2A) and A(3)AR 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 A(2A) and/or A(3)ARs in T/C-28a2 chondrocytes and hFOB 1.19 osteoblasts. Immunofluorescence, mRNA analysis and saturation binding assays revealed that PEMF exposure up-regulated A(2A) and A(3)AR expression. A(2A) and A(3)ARs were able to modulate cAMP production and cell proliferation. The activation of A(2A) and A(3)ARs 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 A(2A) and A(3)AR stimulation on the release of prostaglandin E(2) (PGE(2)), an important lipid inflammatory mediator, was observed. In addition, in T/C-28a2 cells, the activation of A(2A) or A(3)ARs 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 A(2A) or A(3)AR 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 A(2A) or A(3)ARs suggesting their potential therapeutic use in the therapy of inflammatory bone and joint disorders.