Department of Veterinary Clinical Sciences, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, Korea.
BK21 FOUR Future Veterinary Medicine Leading Education and Research Center, Seoul National University, Seoul 08826, Korea.
J Vet Sci. 2024 Sep;25(5):e68. doi: 10.4142/jvs.24147.
A relatively new therapeutic agent for osteoarthritis (OA), polydeoxyribonucleotide (PDRN), shows potential in treating human OA due to its regenerative and anti-inflammatory effects. However, studies on PDRN for canine OA are limited, and no study has investigated their use with mesenchymal stem cells (MSCs) conventionally used for OA treatment.
This study aimed to evaluate the potential of PDRN and explore its combined effect with adipose tissue-derived MSCs (AdMSCs) in treating canine OA.
To study the impact of PDRN, canine chondrocytes, synoviocytes, and AdMSCs were exposed to various PDRN concentrations, and viability was assessed using cell counting kit-8. The OA model was created by treating chondrocytes and synoviocytes with lipopolysaccharide, followed by treatment under three different conditions: PDRN alone, AdMSCs alone, and a combination of PDRN and AdMSCs. Using real-time quantitative polymerase chain reaction, the anti-inflammatory effects and mechanisms were investigated by quantitatively assessing pro-inflammatory cytokines, collagen degradation markers, adenosine A2a receptor (ADORA2A), and nuclear factor-kappa B.
PDRN alone and combined with AdMSCs significantly reduced the expression of pro-inflammatory cytokines and collagen degradation markers in an OA model. PDRN promoted AdMSC proliferation and upregulated ADORA2A expression. AdMSCs exhibited comprehensive anti-inflammatory effects through paracrine effects, and both substances reduced inflammatory gene expression through different mechanisms, potentially enhancing therapeutic effects.
The results indicate that PDRN is a safe and effective anti-inflammatory material that can be used independently or as an adjuvant for AdMSCs. Although additional research is necessary, this study is significant because it provides a foundation for future research at the cellular level.
多聚脱氧核苷酸（PDRN）是一种治疗骨关节炎（OA）的新型治疗药物，由于其再生和抗炎作用，在治疗人类 OA 方面具有潜在作用。然而，关于犬 OA 的 PDRN 研究有限，并且没有研究调查其与间充质干细胞（MSCs）联合使用，这些干细胞通常用于 OA 治疗。
本研究旨在评估 PDRN 的潜力，并探索其与传统用于 OA 治疗的脂肪组织源性 MSCs（AdMSCs）联合使用的效果。
为了研究 PDRN 的影响，用不同浓度的 PDRN 处理犬软骨细胞、滑膜细胞和 AdMSCs，使用细胞计数试剂盒-8 评估细胞活力。用脂多糖处理软骨细胞和滑膜细胞来建立 OA 模型，然后在三种不同条件下进行治疗：单独使用 PDRN、单独使用 AdMSCs、PDRN 和 AdMSCs 联合使用。通过实时定量聚合酶链反应，定量评估促炎细胞因子、胶原降解标志物、腺苷 A2a 受体（ADORA2A）和核因子-κB，研究抗炎效果和机制。
单独使用 PDRN 和与 AdMSCs 联合使用均显著降低 OA 模型中促炎细胞因子和胶原降解标志物的表达。PDRN 促进 AdMSC 增殖并上调 ADORA2A 表达。AdMSCs 通过旁分泌作用发挥全面的抗炎作用，并且两种物质通过不同的机制降低炎症基因的表达，可能增强治疗效果。
结果表明 PDRN 是一种安全有效的抗炎物质，可单独使用或作为 AdMSCs 的佐剂使用。尽管还需要进一步研究，但本研究具有重要意义，因为它为细胞水平的未来研究提供了基础。
