Department and Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Rehabilitation Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.
Sci Rep. 2024 Oct 30;14(1):26076. doi: 10.1038/s41598-024-77264-2.
Osteoarthritis (OA) is a degenerative disease of the joints, prevalent worldwide. Polydeoxyribonucleotide (PDRN) is used for treating knee OA. However, the role of PDRN in IL-1β-induced inflammatory responses in human bone marrow-derived mesenchymal stem cells (hBMSCs) remains unknown. Here, we investigated the role of PDRN in IL-1β-induced impairment of chondrogenic differentiation in hBMSCs. hBMSCs treated with PDRN showed a large micromass, enhanced safranin O and alcian blue staining intensity, and increased expression of chondrogenic genes in IL-1β-induced inflammatory responses, in addition to regulation of catabolic and anabolic genes. In addition, PDRN treatment suppressed the expression of inflammatory cytokines and mitigated IL-1β-induced apoptosis in hBMSCs. Mechanistically, PDRN treatment increased the formation of cyclic adenosine monophosphate (cAMP) and upregulated the phosphorylation of cAMP-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) through the adenosine A2A receptor in hBMSCs and thus blocked the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Thus, IL-1β-induced expression of inflammatory cytokines in hBMSCs was directly reduced by adenosine A2A receptor activation. Based on our results, we suggest that PDRN may be a promising MSC-based therapeutic agent for OA.
骨关节炎（OA）是一种全球性的关节退行性疾病。多聚脱氧核苷酸（PDRN）用于治疗膝骨关节炎。然而，PDRN 在人骨髓间充质干细胞（hBMSCs）中白细胞介素-1β（IL-1β）诱导的炎症反应中的作用尚不清楚。在这里，我们研究了 PDRN 在 IL-1β 诱导的 hBMSCs 软骨分化损伤中的作用。在 IL-1β 诱导的炎症反应中，用 PDRN 处理的 hBMSCs 表现出较大的微团、增强的番红 O 和阿利新蓝染色强度以及软骨形成基因的表达增加，同时调节分解代谢和合成代谢基因。此外，PDRN 处理抑制了 hBMSCs 中炎症细胞因子的表达并减轻了 IL-1β 诱导的细胞凋亡。在机制上，PDRN 处理通过 hBMSCs 中的腺苷 A2A 受体增加环磷酸腺苷（cAMP）的形成并上调 cAMP 依赖性蛋白激酶 A（PKA）/cAMP 反应元件结合蛋白（CREB）的磷酸化，从而阻断核因子κ轻链增强子的 B 细胞激活（NF-κB）信号通路。因此，腺苷 A2A 受体的激活直接减少了 hBMSCs 中白细胞介素-1β诱导的炎症细胞因子的表达。基于我们的结果，我们认为 PDRN 可能是一种有前途的基于 MSC 的 OA 治疗剂。
