The mechanisms driving the pathologic progression of osteoarthritis (OA) have not yet to be fully elucidated. Excessive and irreversible breakdown of the extracellular matrix is the main hallmark of OA. Inhibitors of DPP‐4 have been widely used for over a decade as a treatment for type‐2 diabetes, but the promising function of DPP‐4 inhibitors in chronic inflammatory diseases has only begun to receive attention. Here, we treated human chondrocytes with interleukin‐1β (IL‐1β) with or without teneligliptin to assess the role of DPP‐4 in the enzyme‐driven reduction of type II collagen. Treatment with teneligliptin significantly reduced IL‐1β‐induced expression of tumor necrosis factor α, IL‐6, and IL‐8, generation of reactive oxygen species, increase in metalloproteinase 3 (MMP‐3) and MMP‐13, reduction of tissue inhibitors of matrix metalloproteinase 1 (TIMP‐1) and TIMP‐2, release of lactate dehydrogenase, and activation of the mitogen‐activated protein kinase p38 and nuclear factor κB intracellular signaling pathways, among other things. These findings demonstrate that treatment with teneligliptin may act as a novel therapy to slow or halt disease progression in patients with OA.

中文翻译：

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Teneligliptin 抑制 IL-1β 诱导的人软骨细胞细胞外基质降解。

驱动骨关节炎（OA）病理进展的机制尚未完全阐明。细胞外基质的过度和不可逆分解是 OA 的主要标志。DPP-4 抑制剂作为 2 型糖尿病的治疗方法已被广泛使用十多年，但 DPP-4 抑制剂在慢性炎症性疾病中的有希望的功能才刚刚开始受到关注。在这里，我们用白细胞介素-1β (IL-1β) 处理人类软骨细胞，有或没有特力列汀，以评估 DPP-4 在酶驱动的 II 型胶原蛋白减少中的作用。特力列汀治疗显着降低了 IL-1β 诱导的肿瘤坏死因子 α、IL-6 和 IL-8 的表达，活性氧的产生，金属蛋白酶 3（MMP-3）和 MMP-13 的增加，减少基质金属蛋白酶 1 (TIMP-1) 和 TIMP-2 的组织抑制剂，释放乳酸脱氢酶，激活丝裂原活化蛋白激酶 p38 和核因子 κB 细胞内信号通路等。这些发现表明，特力列汀治疗可作为减缓或阻止 OA 患者疾病进展的新疗法。