Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A_2A Receptor Involvement

Abstract

Polydeoxyribonucleotides (PDRNs) are low molecular weight DNA molecules of natural origin that stimulate cell migration and growth, extracellular matrix (ECM) protein production, and reduce inflammation. Most preclinical and clinical studies on tissue regeneration with PDRNs focused on skin, and only few are about musculoskeletal tissues. Starting from an overview on skin regeneration studies, through the analysis of in vitro, in vivo, and clinical studies (1990-2016), the present review aimed at defining the effects of PDRN and their mechanisms of action in the regeneration of musculoskeletal tissues. This would also help future researches in this area. A total of 29 studies were found by PubMed and www.webofknowledge.com searches: 20 were on skin (six in vitro, six in vivo, one vitro/vivo, seven clinical studies), while the other nine regarded bone (one in vitro, two in vivo, one clinical studies), cartilage (one in vitro, one vitro/vivo, two clinical studies), or tendon (one clinical study) tissues regeneration. PDRNs improved cell growth, tissue repair, ECM proteins, physical activity, and reduced pain and inflammation, through the activation of adenosine A receptor. PDRNs are currently used for bone, cartilage, and tendon diseases, with a great variability regarding the PDRN dosage to be used in clinical practice, while the dosage for skin regeneration is well established. PDRNs are usually administered from a minimum of three to a maximum of five times and they act trough the activation of A receptor. Further studies are advisable to confirm the effectiveness of PDRNs and to standardize the PDRN dose. J. Cell. Physiol. 232: 2299-2307, 2017. © 2016 Wiley Periodicals, Inc.

Polydeoxyribonucleotide Exerts Therapeutic Effect by Increasing VEGF and Inhibiting Inflammatory Cytokines in Ischemic Colitis Rats

“…Polydeoxyribonucleotide (PDRN) is a mixture of nucleotides with molecular weights of 50-1500 kDa that originates from the human placenta or salmon sperm [17]. PDRN facilitates skin regeneration by activating adenosine A 2A receptor (A 2A R) [17]. A 2A R is involved in the anti-inflammatory pathway and in the VEGF production [17,18].…”

“…PDRN facilitates skin regeneration by activating adenosine A 2A receptor (A 2A R) [17]. A 2A R is involved in the anti-inflammatory pathway and in the VEGF production [17,18]. PDRN inhibits apoptosis and exerts anti-inflammatory effect by suppressing the production of inflammatory cytokines [12,18].…”

An effective range of polydeoxyribonucleotides is critical for wound healing quality

“…Effect of PDRN size on wound closure in mice skin. Multiple previous studies have demonstrated that PDRNs promote wound healing in various animal models (6,10,(18)(19)(20). To evaluate the effect of PDRNs on wound healing, 8-week old hairless (SKH1) mice were given different sizes of PDRNs daily for a week.…”

“…A number of previous studies have demonstrated that classic PDRN functions as a growth promoter in the regeneration of various tissues, including wounded skin, and in osteoarthritis and ischemic-reperfusion injuries (10,29,30). Based on the beneficial effects of PDRN, the effects of different molecular size DNA mixtures on wound healing were investigated.…”

“…Classic PDRN is an A 2A receptor agonist (10,11). Multiple in vitro and in vivo studies demonstrated that PDRN serves as an anti-inflammatory and tissue-regenerating agent.…”