Effects of heat deproteinate bone and polynucleotides on bone regeneration: An experimental study on rat

Guizzardi, Stefano; Martini, Désirèe; Bacchelli, Beatrice; Valdatta, Luigi; Thioné, Alessandro; Scamoni, Stefano; Uggeri, Jacopo; Ruggeri, Alessandro

doi:10.1016/j.micron.2007.05.003

Cited by 25 publications

(26 citation statements)

References 25 publications

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“…It has been suggested that PDRN accelerates the repair and the growth of bone tissue (Guizzardi et al, 2007). Furthermore, PDRN effects were investigated in a model of diabetes-impaired wound healing (Galeano et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Activity and Clinical Use of PDRN

et al. 2017

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PDRN is a proprietary and registered drug that possesses several activities: tissue repairing, anti-ischemic, and anti-inflammatory. These therapeutic properties suggest its use in regenerative medicine and in diabetic foot ulcers. PDRN holds a mixture of deoxyribonucleotides with molecular weights ranging between 50 and 1,500 KDa, it is derived from a controlled purification and sterilization process of Oncorhynchus mykiss (Salmon Trout) or Oncorhynchus keta (Chum Salmon) sperm DNA. The procedure guarantees the absence of active protein and peptides that may cause immune reactions. In vitro and in vivo experiments have suggested that PDRN most relevant mechanism of action is the engagement of adenosine A2A receptors. Besides engaging the A2A receptor, PDRN offers nucleosides and nucleotides for the so called “salvage pathway.” The binding to adenosine A2A receptors is a unique property of PDRN and seems to be linked to DNA origin, molecular weight and manufacturing process. In this context, PDRN represents a new advancement in the pharmacotherapy. In fact adenosine and dipyridamole are non-selective activators of adenosine receptors and they may cause unwanted side effects; while regadenoson, the only other A2A receptor agonist available, has been approved by the FDA as a pharmacological stress agent in myocardial perfusion imaging. Finally, defibrotide, another drug composed by a mixture of oligonucleotides, has different molecular weight, a DNA of different origin and does not share the same wound healing stimulating effects of PDRN. The present review analyses the more relevant experimental and clinical evidences carried out to characterize PDRN therapeutic effects.

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Section: Introductionmentioning

confidence: 99%

Pharmacological Activity and Clinical Use of PDRN

et al. 2017

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“…PDRN is a compound formed by a mixture of deoxyribonucleotide polymers of different lengths and nucleosides derived from salmon trout ( Oncorhynchus mykiss ) sperm by a process that guarantees a high percentage of DNA and the absence of active proteins or peptides (Guizzardi et al, 2003). PDRN effects were documented in several experimental models (Lazzarotto et al, 2004; Guizzardi et al, 2007; Bitto et al, 2008; Galeano et al, 2008; Altavilla et al, 2009; Kim et al, 2014). Furthermore, as adenosine and its analogs, it can stimulate sperm functional ability in mouse (Fraser and Duncan, 1993).…”

Section: Introductionmentioning

confidence: 99%

Polydeoxyribonucleotide, an Adenosine-A2A Receptor Agonist, Preserves Blood Testis Barrier from Cadmium-Induced Injury

et al. 2017

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Cadmium (Cd) impairs blood-testis barrier (BTB). Polydeoxyribonucleotide (PDRN), an adenosine A2A agonist, has positive effects on male reproductive system. We investigated the effects of PDRN on the morphological and functional changes induced by Cd in mice testes. Adult Swiss mice were divided into four groups: controls administered with 0.9% NaCl (1 ml/kg, i.p., daily) or with PDRN (8 mg/kg, i.p. daily), animals challenged with Cd chloride (CdCl2; 2 mg/kg, i.p, daily) and animals challenged with CdCl2 (2 mg/kg, i.p., daily) and treated with PDRN (8 mg/kg, i.p., daily). Experiments lasted 14 days. Testes were processed for biochemical, structural, and ultrastructural evaluation and hormones were assayed in serum. CdCl2 increased pERK 1/2 expression and Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels; it decreased testosterone (TE) and inhibin-B levels and induced structural damages in extratubular compartment and in seminiferous epithelium, with ultrastructural features of BTB disruption. Many TUNEL-positive germ cells were present. CdCl2 increased tubular TGF-β3 immunoreactivity and reduced claudin-11, occludin, and N-cadherin immunoreactivity. PDRN administration reduced pERK 1/2 expression, FSH, and LH levels; it increased TE and inhibin-B levels, ameliorated germinal epithelium changes and protected BTB ultrastructure. Few TUNEL-positive germ cells were present and the extratubular compartment was preserved. Furthermore, PDRN decreased TGF-β3 immunoreactivity and enhanced claudin-11, occludin, and N-cadherin immunoreactivity. We demonstrate a protective effect of PDRN on Cd-induced damages of BTB and suggest that PDRN may play an important role against Cd, particularly against its harmful effects on gametogenesis.

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“…Studies on musculoskeletal tissue regeneration were conducted on: (1) bone tissue, one in vitro on osteoblasts (OBs) (Guizzardi et al, ), two in vivo in rat bone defects and subcutaneous pockets (Guizzardi et al, ; Kim et al, ) and one in patients affected by ischiofemoral impingement syndrome (IFI) (Kim et al, ); (2) cartilage tissue, one in vitro on cartilage explants (Gennero et al, ), two in patients affected by knee OA (Vanelli et al, ; Giarratana et al, ) and one both in vitro, on chondrocytes from patients affected by rheumatoid arthritis (RA), and in vivo in mice affected by arthritis (CIA) (Bitto et al, ); (3) tendon tissue in patients affected by plantar fasciitis (Kim and Chung, ).…”

Section: Resultsmentioning

confidence: 99%

“…In rats with tibiae bone defects, the combination of PDRNs and deproteinated porcine cortical bone (HDB), employed to fill the defects, increased bone ingrowth and repair more than when these were used separately (Guizzardi et al, ). In addition, human demineralized dentin matrix (DDM) in a PDRN solution induced new bone formation in subcutaneous pockets performed on the dorsum of nude mice after 4 weeks from implantation (Kim et al, ).…”

Section: Resultsmentioning

confidence: 99%

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

Veronesi

Carubbi

Martini

et al. 2017

Journal Cellular Physiology

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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.

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Effects of heat deproteinate bone and polynucleotides on bone regeneration: An experimental study on rat

Cited by 25 publications

References 25 publications

Pharmacological Activity and Clinical Use of PDRN

Pharmacological Activity and Clinical Use of PDRN

Polydeoxyribonucleotide, an Adenosine-A2A Receptor Agonist, Preserves Blood Testis Barrier from Cadmium-Induced Injury

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

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Effects of heat deproteinate bone and polynucleotides on bone regeneration: An experimental study on rat

Cited by 25 publications

References 25 publications

Pharmacological Activity and Clinical Use of PDRN

Pharmacological Activity and Clinical Use of PDRN

Polydeoxyribonucleotide, an Adenosine-A2A Receptor Agonist, Preserves Blood Testis Barrier from Cadmium-Induced Injury

Polydeoxyribonucleotides (PDRNs) From Skin to Musculoskeletal Tissue Regeneration via Adenosine A2A Receptor Involvement

Contact Info

Product

Resources

About

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