Polydeoxyribonucleotide reduces cytokine production and the severity of collagen‐induced arthritis by stimulation of adenosine A 2A receptor
Abstract
Objective: Broad antiinflammatory effects following adenosine A 2A receptor stimulation have been demonstrated in acute inflammatory diseases, including arthritis. Polydeoxyribonucleotide (PDRN) activates the adenosine A 2A receptor. This study was undertaken to investigate the effects of PDRN in collagen‐induced arthritis (CIA) in mice. Methods: Arthritis was induced in DBA/1 mice by an intradermal injection of 100 μl of bovine type II collagen in Freund's complete adjuvant. Mice were immunized a second time 21 days later. Control animals received 100 μl of a saline solution. Animals with CIA were randomized to receive one of the following: vehicle (1 ml/kg); PDRN (8 mg/kg intraperitoneally daily); 3,7‐dimethyl‐propargylxanthine (DMPX), a specific adenosine A 2A receptor antagonist (0.1 mg/kg intraperitoneally daily); or PDRN plus DMPX. The treatment was initiated immediately after the second immunization and continued to day 45. Clinical evaluation of arthritis was performed throughout the study. On day 45, the animals were killed and the severity of arthritis was evaluated histologically. Cartilage expression and circulating levels of high mobility group box chromosomal protein 1 (HMGB‐1), tumor necrosis factor α (TNFα), interleukin‐6 (IL‐6), and IL‐10 were investigated. Inflammatory cytokine production was also evaluated in stimulated human chondrocytes treated with PDRN. Results: PDRN treatment significantly ameliorated clinical signs of arthritis, improved histologic damage, reduced the cartilage expression and circulating levels of HMGB‐1, TNFα, and IL‐6, and enhanced IL‐10 expression. The concomitant administration of DMPX and PDRN ablated the PDRN‐induced protective effect in experimental arthritis. PDRN also reduced cytokine production from stimulated human chondrocytes. Conclusion: Our findings indicate that PDRN may represent a new alternative for the treatment of arthritis.
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PDRN downregulates MMP-1, initiating the collagen synthesis cascade and enhancing collagen production in dermal fibroblasts.
“In addition, PDRN downregulates matrix metalloproteinase-1 (MMP-1), initiating the collagen synthesis cascade and enhancing collagen production in dermal fibroblasts [70].”
From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [70]
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Adenosine Receptors as Therapeutic Targets
Jacobson, K. A., & Gao, Z.-G. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1983 · Cited by 1,431 · see citing works
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Novel Anti-Melanogenesis Properties of Polydeoxyribonucleotide, a Popular Wound Healing Booster
Noh, T., Chung, B., Kim, S., Lee, M., Kim, M., Youn, C., Lee, M., & Chang, S. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17091448 · Cited by 68 · see citing works
Irrera, N., Bitto, A., Vaccaro, M., Mannino, F., Squadrito, V., Pallio, G., Arcoraci, V., Minutoli, L., Ieni, A., Lentini, M., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041215 · Cited by 41 · see citing works
Self-citationPolydeoxyribonucleotide Regulation of Inflammation
Colangelo, M. T., Galli, C., & Guizzardi, S. (2020) · Advances in Wound Care · doi:10.1089/wound.2019.1031 · Cited by 33 · see citing works
Kim, S. T. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17081024 · Cited by 18 · see citing works
- Authors
- Bitto, A., Polito, F., Irrera, N., D'Ascola, A., Avenoso, A., Nastasi, G., Campo, G. M., Micali, A., Bagnato, G., Minutoli, L., Marini, H., Rinaldi, M., Squadrito, F., & Altavilla, D.
- Affiliations
- University of Messina (IT)
- ORCID
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2011-10-28
- Volume
- 63
- Issue
- 11
- Pages
- 3364-3371
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2094344379
- Cited by
- 105
- References
- 1
- Citations by year
- 2026: 12 · 2025: 13 · 2024: 4 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 9 · 2019: 9 · 2018: 10 · 2017: 10 · 2016: 8 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 2
- FWCI
- 2.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Keywords
- polydeoxyribonucleotide, collagen-induced arthritis, adenosine A2A receptor, anti-inflammatory therapy, cytokine production, HMGB1, TNF-α, interleukin-6, IL-10, chondrocytes, cartilage damage, DMPX, adenosine receptor antagonists
- MeSH terms
- Animals, Arthritis, Experimental, Cartilage, Articular, Male, Polydeoxyribonucleotides, Severity of Illness Index, Tumor Necrosis Factor-alpha, Interleukin-6, Interleukin-10, Chondrocytes, Collagen Type II, HMGB1 Protein, Mice, Adenosine A2 Receptor Agonists
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