Targeting Adenosine Signalling in Knee Chondropathy PEMF

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Int. J. Mol. Sci. 2023, 24, 10090
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reading titles and reviewing abstracts. A total of 6 additional abstracts were identified by checking the references of the relevant papers. A total of 60 articles were finally included in the present review.
3. Results
3.1. A2A Receptors
Adenosine plays a significant role in defending human health against many patholo- gies by exerting several protective effects against cell damage, in both the brain and the periphery, through interaction with A1, A2A, A2B, and A3 adenosine receptors (ARs) [4].
In clinical biophysics, low-frequency low-energy pulsed electromagnetic fields (PEMF) are a fundamental tool for investigating the development and the importance of physical stimuli in the control of biological activities. Many in vivo or in vitro studies have been per- formed to identify the biophysical stimulation induced by PEMF as a potential alternative to pharmacological treatments in several inflammatory-related pathologies [5–7].
Cartilage lesions are reported to represent a major health problem and contribute to the highest rate of world disability due to the body’s limited cartilage regeneration capability. In recent decades, several studies have been developed to resolve this cause of disability, some of them with physical stimuli approaches. From a cellular point of view, a wide body of in vitro studies has investigated the effect of PEMF on chondrocytes and synoviocytes.
ARs are expressed in these cell lines with variable density. In the presence of PEMFs, only A2A and A3ARs are increased, whereas A1 and A2BARs show binding parameters similar to those of control cells [8]. After PEMF treatment, A2A and A3AR agonists reveal an amplified effect on cAMP production that is blocked by selective A2A and A3AR antagonists [8].
The PEMF’s transmembrane signal recognition processes were first reported by Varani et al. [9]. These authors found that ARs were the primary target of PEMF stimulation in inflammatory cells; ARs play a major role in the control of inflammatory processes, with both pro-inflammatory and anti-inflammatory effects. PEMF exposure has been shown to increase A2A and A3AR density in cell membranes of osteoblasts, chondrocytes, and synoviocytes [10]. In addition, it inhibits IL-6 and IL-8 cytokines, while stimulating the release of the anti-inflammatory cytokine IL-10 and inhibited prostaglandin E2 (PGE2) pro- duction with up-regulation of A (2A) receptors [11]. IL-1β is a pro-inflammatory cytokine that promotes ECM cartilage degradation in healthy and osteoarthritic-joint-derived cells. In a study performed on cartilage explants, it was reported that PEMF inhibits the negative effect of IL-1β cytokine [12].
3.2. Polydeoxiriboneucleotides
Polydeoxyribonucleotides (PDRNs) are a family of DNA-derived drugs, character- ized by a molecular weight of 50–1500 kDa, that derive from a standardized process of purification and sterilization of sperm DNA from Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) (Figure 1) [13].