Electromagnetic fields (EMFs) and adenosine receptors modulate prostaglandin E₂ and cytokine release in human osteoarthritic synovial fibroblasts

Abstract

Synovial fibroblasts (SFs) contribute to the development of osteoarthritis (OA) by the secretion of a wide range of pro-inflammatory mediators, including cytokines and lipid mediators of inflammation. Previous studies suggest that electromagnetic fields (EMFs) may represent a potential therapeutic approach to limit cartilage degradation and control inflammation associated to OA, and that they may act through the adenosine pathway. Therefore, we investigated whether EMFs might modulate inflammatory activities of human SFs from OA patients (OASFs) treated with interleukin-1β (IL-1β), and the possible involvement of adenosine receptors (ARs) in mediating EMF effects. EMF exposure induced a selective increase in A(2A) and A(3) ARs. These increases were associated to changes in cAMP levels, indicating that ARs were functionally active also in EMF-exposed cells. Functional data obtained in the presence of selective A(2A) and A(3) adenosine agonists and antagonists showed that EMFs inhibit the release of prostaglandin E(2) (PGE(2)) and the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8), while stimulating the release of interleukin-10 (IL-10), an antinflammatory cytokine. These effects seem to be mediated by the EMF-induced upregulation of A(2A) and A(3) ARs. No effects of EMFs or ARs have been observed on matrix degrading enzyme production. In conclusion, this study shows that EMFs display anti-inflammatory effects in human OASFs, and that these EMF-induced effects are in part mediated by the adenosine pathway, specifically by the A(2A) and A(3) AR activation. Taken together, these results open new clinical perspectives to the control of inflammation associated to joint diseases.

The A3Adenosine Receptor: History and Perspectives

“…Moreover, PEMFs are able to mediate the upregulation of A 3 ARs in bovine chondrocytes and synoviocytes (Varani et al, 2008;De Mattei et al, 2009). These data have been further confirmed in human synoviocytes where the copresence of A 3 ARs and PEMFs reduces the release of PGE2, IL-6, and IL-8, whereas it increases IL-10 release (Ongaro et al, 2012). Recently, in human T/C-28a2 chondrocytes and human FOB 1.19 osteoblasts, PEMFs and A 3 AR stimulation have been seen to reduce PGE2, IL-6, and IL-8 production, suggesting their potential in the treatment of inflammatory bone and joint disorders .…”

Efficacy of extremely low-frequency magnetic field in fibromyalgia pain: A pilot study

“…The algogenic effect of electromagnetic fields has also been observed with pulsed MFs in osteoarthritic disease [45][46]. Musaev and colleagues reported that lowfrequency pulsed MFs have analgesic, vasoactive, neuronstimulating, and trophic effects in patients with diabetic polyneuropathy, which has a similar sensory profile as FM [26].…”

Purinergic signalling in the musculoskeletal system

“…Electromagnetic field stimulation led to up-regulation of A 2A receptors in synovial fibroblasts and it was suggested that adenosine, acting through both A 1 and A 2A receptors, had anti-inflammatory activity to control joint inflammation [443]. A 2A and A 3 receptor agonists have been shown to modulate PGE 2 and cytokine release in human osteoarthritic fibroblasts [444]. Adenosine receptors also regulate inflammatory responses in human synoviocytes [445].…”