The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
Division of Rheumatology, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Republic of Korea.
Immunol Lett. 2020 Dec;228:112-121. doi: 10.1016/j.imlet.2020.10.008. Epub 2020 Nov 1.
Disease-modifying osteoarthritis (OA) therapy is not yet available. Several adjuvant therapies have demonstrated promising results in the treatment of OA. The present study aimed to investigate the therapeutic effects and underlying mechanisms of a combination of Lactobacillus acidophilus, vitamin B, and curcumin in the treatment of OA. Monosodium iodoacetate (MIA)-induced arthritis of the knee joint in rat was used as an animal model of human OA. The combination of L. acidophilus LA-1, vitamin B, and curcumin or a saline solution was given orally. Pain was measured according to the paw withdrawal latency, and paw withdrawal threshold. Cartilage destruction was analyzed using histomorphological techniques and the Mankin scoring system. Protein expression in the joint was examined using immunohistochemistry. The effects of the combination of L. acidophilus LA-1, vitamin B, and curcumin on mRNA levels in chondrocytes stimulated with interleukin (IL)-1β were analyzed using real-time polymerase chain reaction. The combination of L. acidophilus, vitamin B, and curcumin effectively downregulated Th17 cells and the related cytokine IL-17, thereby maintained the Treg population, and increased the expression of the Treg-related cytokine IL-10 in human peripheral blood mononuclear cells. The OA animal model exhibited reduced pain and preservation of cartilage in response to the combination treatment. The expression levels of pro-inflammatory cytokines and the catabolic, matrix metalloproteinase-13 (MMP-13), were decreased, whereas the expression of the anabolic tissue inhibitors of metalloproteinases (TIMPs) were upregulated in response to the drug combination. The combination of L. acidophilus, vitamin B, and curcumin was beneficial in OA treatment, controlling the inflammatory response via regulation of the Th17/Treg population and reducing the expression of pro-inflammatory cytokines in human peripheral blood mononuclear cells. The combination treatment also preserved cartilage, suppressed osteoclastogenesis, and regulated the anabolic/catabolic imbalance. These findings indicate the therapeutic potential of combination use of L. acidophilus, vitamin B, and curcumin in patients with OA.
治疗骨关节炎（OA）的药物尚未问世。几种辅助疗法已在 OA 的治疗中显示出良好的效果。本研究旨在探讨嗜酸乳杆菌、维生素 B 和姜黄素联合治疗 OA 的治疗效果及作用机制。利用 MIA 诱导的大鼠膝关节骨关节炎作为人类 OA 的动物模型。采用嗜酸乳杆菌 LA-1、维生素 B 和姜黄素或生理盐水口服治疗。根据足底潜伏期和足底回缩阈值测量疼痛。采用组织形态学技术和 Mankin 评分系统分析软骨破坏。采用免疫组化法检测关节蛋白表达。采用实时聚合酶链反应分析嗜酸乳杆菌 LA-1、维生素 B 和姜黄素联合作用对白细胞介素（IL）-1β刺激的软骨细胞中 mRNA 水平的影响。嗜酸乳杆菌、维生素 B 和姜黄素联合治疗有效地下调了 Th17 细胞及其相关细胞因子 IL-17，从而维持了 Treg 群体，增加了 Treg 相关细胞因子 IL-10 的表达。OA 动物模型对联合治疗的反应表现为疼痛减轻和软骨保存。促炎细胞因子和分解代谢、基质金属蛋白酶-13（MMP-13）的表达水平降低，而药物联合治疗后组织抑制剂的金属蛋白酶（TIMP）的表达水平升高。嗜酸乳杆菌、维生素 B 和姜黄素联合治疗对 OA 有益，通过调节 Th17/Treg 群体控制炎症反应，减少人外周血单个核细胞中促炎细胞因子的表达。联合治疗还可保存软骨，抑制破骨细胞生成，并调节合成代谢/分解代谢失衡。这些发现表明嗜酸乳杆菌、维生素 B 和姜黄素联合使用在 OA 患者中的治疗潜力。
