The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, 33014 Tampere, Finland.
Coxa Hospital for Joint Replacement, 33520 Tampere, Finland.
Int J Mol Sci. 2023 Jun 13;24(12):10057. doi: 10.3390/ijms241210057.
Transient receptor potential (TRP) ion channels are expressed in neuronal and some non-neuronal cells and are involved particularly in pain and thermosensation. We previously showed that TRPA1 is functionally expressed in human osteoarthritic (OA) chondrocytes and mediates inflammation, cartilage degradation, and pain in monosodium-iodoacetate-induced experimental OA. In the present study, we explored the expression of TRP-channels in primary human OA chondrocytes and investigated whether drugs used in the treatment of OA, ibuprofen and glucocorticoids, have effects on TRP-channel expression. OA cartilage was obtained from knee replacement surgery and chondrocytes were isolated with enzyme digestion. NGS analysis showed the expression of 19 TRP-genes in OA chondrocytes, with TRPM7, TRPV4, TRPC1, and TRPM8 having the highest counts in unstimulated cells. These results were verified with RT-PCR in samples from a different group of patients. Interleukin-1β (IL-1β) significantly increased TRPA1 expression, while TRPM8 and TRPC1 expression was decreased, and TRPM7 and TRPV4 expression remained unaffected. Furthermore, dexamethasone attenuated the effect of IL-1β on TRPA1 and TRPM8 expression. The TRPM8 and TRPA1 agonist menthol increased the expression of the cartilage-degrading enzymes MMP-1, MMP-3, and MMP-13 and the inflammatory factors iNOS and IL-6 in OA chondrocytes. In conclusion, human OA chondrocytes express 19 different TRP-genes, of which the significant TRPM8 expression is a novel finding. Dexamethasone attenuated IL-1β-induced TRPA1 expression. Interestingly, the TRPM8 and TRPA1 agonist menthol increased MMP expression. These results support the concept of TRPA1 and TRMP8 as potential novel drug targets in arthritis.
瞬时受体电位 (TRP) 离子通道存在于神经元和一些非神经元细胞中，尤其参与疼痛和热敏感觉。我们之前的研究表明，TRPA1 在人类骨关节炎 (OA) 软骨细胞中具有功能性表达，并介导单碘乙酸钠诱导的实验性 OA 中的炎症、软骨降解和疼痛。在本研究中，我们探讨了 TRP 通道在原代人 OA 软骨细胞中的表达，并研究了用于 OA 治疗的药物，布洛芬和糖皮质激素，是否对 TRP 通道表达有影响。OA 软骨取自膝关节置换手术，软骨细胞用酶消化法分离。NGS 分析显示 19 种 TRP 基因在 OA 软骨细胞中的表达，TRPM7、TRPV4、TRPC1 和 TRPM8 在未刺激细胞中的计数最高。这些结果在来自不同患者组的样本中通过 RT-PCR 得到了验证。白细胞介素-1β（IL-1β）显著增加了 TRPA1 的表达，而 TRPM8 和 TRPC1 的表达则降低，TRPM7 和 TRPV4 的表达则不受影响。此外，地塞米松减弱了 IL-1β 对 TRPA1 和 TRPM8 表达的影响。TRPM8 和 TRPA1 激动剂薄荷醇增加了 OA 软骨细胞中软骨降解酶 MMP-1、MMP-3 和 MMP-13 以及炎症因子 iNOS 和 IL-6 的表达。总之，人 OA 软骨细胞表达 19 种不同的 TRP 基因，其中显著的 TRPM8 表达是一个新发现。地塞米松减弱了 IL-1β 诱导的 TRPA1 表达。有趣的是，TRPM8 和 TRPA1 激动剂薄荷醇增加了 MMP 的表达。这些结果支持 TRPA1 和 TRMP8 作为关节炎潜在的新型药物靶点的概念。
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