Targeting Adenosine Signalling in Knee Chondropathy: The Combined Action of Polydeoxyribonucleotide and Pulsed Electromagnetic Fields: A Current Concept Review

Abstract

Chondropathy of the knee is one of the most frequent degenerative cartilage pathologies with advancing age. Scientific research has, in recent years, advanced new therapies that target adenosine A2 receptors, which play a significant role in human health against many disease states by activating different protective effects against cell sufferance and damage. Among these, it has been observed that intra-articular injections of polydeoxyribonucleotides (PDRN) and Pulsed Electromagnetic Fields (PEMF) can stimulate the adenosine signal, with significant regenerative and healing effects. This review aims to depict the role and therapeutic modulation of A2A receptors in knee chondropathy. Sixty articles aimed at providing data for our study were included in this review. The present paper highlights how intra-articular injections of PDRN create beneficial effects by reducing pain and improving functional clinical scores, thanks to their anti-inflammatory action and the important healing and regenerating power of the stimulation of cell growth, production of collagen, and the extracellular matrix. PEMF therapy is a valid option in the conservative treatment of different articular pathologies, including early OA, patellofemoral pain syndrome, spontaneous osteonecrosis of the knee (SONK), and in athletes. PEMF could also be used as a supporting therapy after an arthroscopic knee procedure total knee arthroplasty to reduce the post-operative inflammatory state. The proposal of new therapeutic approaches capable of targeting the adenosine signal, such as the intra-articular injection of PDRN and the use of PEMF, has shown excellent beneficial results compared to conventional treatments. These are presented as an extra weapon in the fight against knee chondropathy.

Keywords: A2A receptor; PEMF; Pulsed Electromagnetic Fields; adenosine signalling; knee chondropathy; polydeoxyribonucleotide (PDRN).

Figure 1

PDRN structure and therapeutic implications.

Figure 2

PEMF and PDRN synergism on the A2A receptors’ intracellular signalling. The figure shows the synergic activation of A2A receptors by PEMF and PDRN. A2A receptors belong to the G protein-coupled receptor (GPCR) family and are coupled with G stimulatory proteins (Gs). PEMF and PDRN activate the A2A receptor, thus causing Adenyl cyclase activation. The subsequent cyclic Adenosine Monophosphate (cAMP) intra-articular concentration finally leads to Protein Kinase A (PKA) activation, which causes, in turn, specific intracellular activation pathways (NF-KB: nuclear factor kappa-light-chain-enhancer of activated B cells; CREB: cAMP response element-binding protein; HIF: Hypoxia-inducible factor).