Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Cracow, Poland.
Int J Mol Sci. 2020 Oct 6;21(19):7381. doi: 10.3390/ijms21197381.
Osteoarthritis (OA) is a degenerative joint disease manifested by movement limitations and chronic pain. Endocannabinoid system (ECS) may modulate nociception via cannabinoid and TRPV1 receptors. The purpose of our study was to examine alterations in the spinal and joint endocannabinoid system during pain development in an animal model of OA. Wistar rats received intra-articular injection of 3mg of sodium monoiodoacetate (MIA) into the knee joint. Animals were sacrificed on day 2, 7, 14, 21, 28 after injection and lumbar spinal cord, cartilage and synovium were collected. Changes in the transcription levels of the ECS elements were measured. At the spinal level, gene expression levels of the cannabinoid and TRPV1 receptors as well as enzymes involved in anandamide synthesis and degradation were elevated in the advanced OA phase. In the joint, an important role of the synovium was demonstrated, since cartilage degeneration resulted in attenuation of the changes in the gene expression. Enzymes responsible for anandamide synthesis and degradation were upregulated particularly in the early stages of OA, presumably in response to early local joint inflammation. The presented study provides missing information about the MIA-induced OA model and encourages the development of a therapy focused on the molecular role of ECS.
骨关节炎（OA）是一种退行性关节疾病，表现为运动受限和慢性疼痛。内源性大麻素系统（ECS）可能通过大麻素和 TRPV1 受体来调节伤害感受。我们研究的目的是在 OA 动物模型中检查疼痛发展过程中脊髓和关节内源性大麻素系统的变化。Wistar 大鼠膝关节内注射 3mg 单碘乙酸钠（MIA）。注射后第 2、7、14、21、28 天处死动物，收集腰椎脊髓、软骨和滑膜。测量 ECS 元素转录水平的变化。在脊髓水平，大麻素和 TRPV1 受体以及参与花生四烯酸合成和降解的酶的基因表达水平在 OA 晚期升高。在关节中，滑膜发挥了重要作用，因为软骨退化导致基因表达变化减弱。负责花生四烯酸合成和降解的酶在 OA 的早期阶段被上调，可能是对早期局部关节炎症的反应。本研究提供了关于 MIA 诱导的 OA 模型的缺失信息，并鼓励开发一种针对 ECS 分子作用的治疗方法。
