Effects of Diclofenac Etalhyaluronate (SI-613/ONO-5704) on Cartilage Degeneration in Arthritic Rats and Inflammatory Cytokine-Stimulated Human Chondrocytes.

IF 2.7 4区医学 Q1 ORTHOPEDICS

CARTILAGE Pub Date : 2024-02-05 DOI:10.1177/19476035231224050

Shuhei Takada, Risa Nodera, Keiji Yoshioka

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Abstract

Objective: Cartilage degeneration is a key feature of osteoarthritis (OA) and rheumatoid arthritis and is thought to negatively impact patients' quality of life. Diclofenac etalhyaluronate (DEH, SI-613/ONO-5704) is a hyaluronic acid (HA) derivative chemically bound to diclofenac (DF) that has been reported to improve OA symptoms; however, its effect on cartilage degeneration remains unknown. In the present study, we investigated the chondroprotective effect of DEH in rats with collagen-induced arthritis and interleukin-1β-stimulated human chondrocytes.

Design: Rats with collagen-induced arthritis were administered DEH and HA intra-articularly, and DF orally. Knee joint swelling, histological scores of articular cartilage, and inflammatory (Il1b) and catabolic (Mmp3 and Mmp13) gene expression in the synovial tissue and cartilage were evaluated. In vitro direct effects of DEH on matrix metalloproteinase (MMP)-3 and MMP-13 expression were examined in interleukin-1β-stimulated human chondrocytes.

Results: In a rat model of collagen-induced arthritis, a single intra-articular dose of DEH inhibited knee joint inflammation and cartilage degeneration. Daily oral administration of DF had similar effects. Conversely, HA administered as a single intra-articular dose had no effect. Only DEH inhibited Mmp3 gene expression in the cartilage, whereas DEH and DF inhibited Mmp3 and Mmp13 mRNA expression in the synovial tissue. In interleukin-1β-stimulated human chondrocytes, DEH and HA inhibited MMP-3 and MMP-13 production, whereas DF had no effect.

Conclusions: In this study, we demonstrated the chondroprotective effect of DEH in rats with collagen-induced arthritis and in interleukin-1β-stimulated human chondrocytes. Thus, DEH may suppress cartilage degeneration in patients with musculoskeletal diseases, such as OA.

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双氯芬酸乙醛脲酸酯（SI-613/ONO-5704）对关节炎大鼠软骨退变和炎性细胞因子刺激人软骨细胞的影响

目的：软骨退化是骨关节炎（OA）和类风湿性关节炎的主要特征，被认为会对患者的生活质量产生负面影响。双氯芬酸乙醛脲酸酯（DEH，SI-613/ONO-5704）是一种与双氯芬酸（DF）化学结合的透明质酸（HA）衍生物，有报道称它能改善 OA 症状；然而，它对软骨退化的影响仍然未知。在本研究中，我们研究了DEH对胶原诱导的关节炎大鼠和白细胞介素-1β刺激的人类软骨细胞的软骨保护作用：设计：给胶原蛋白诱导的关节炎大鼠关节内注射DEH和HA，口服DF。对膝关节肿胀、关节软骨组织学评分、滑膜组织和软骨中炎症（Il1b）和分解（Mmp3 和 Mmp13）基因表达进行评估。体外研究了白细胞介素-1β刺激的人软骨细胞中 DEH 对基质金属蛋白酶（MMP）-3 和 MMP-13 表达的直接影响：结果：在胶原蛋白诱导的大鼠关节炎模型中，单次关节内注射 DEH 可抑制膝关节炎症和软骨退化。每日口服 DF 也有类似效果。相反，单次关节内给药的 HA 则没有效果。只有 DEH 抑制了软骨中 Mmp3 基因的表达，而 DEH 和 DF 则抑制了滑膜组织中 Mmp3 和 Mmp13 mRNA 的表达。在白细胞介素-1β刺激的人软骨细胞中，DEH和HA抑制了MMP-3和MMP-13的产生，而DF则没有影响：在这项研究中，我们证实了 DEH 对胶原诱导的关节炎大鼠和白细胞介素-1β刺激的人类软骨细胞具有软骨保护作用。因此，DEH 可抑制肌肉骨骼疾病（如 OA）患者的软骨退化。

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来源期刊

CARTILAGE ORTHOPEDICS-

CiteScore

6.90

自引率

7.10%

发文量

期刊介绍： CARTILAGE publishes articles related to the musculoskeletal system with particular attention to cartilage repair, development, function, degeneration, transplantation, and rehabilitation. The journal is a forum for the exchange of ideas for the many types of researchers and clinicians involved in cartilage biology and repair. A primary objective of CARTILAGE is to foster the cross-fertilization of the findings between clinical and basic sciences throughout the various disciplines involved in cartilage repair. The journal publishes full length original manuscripts on all types of cartilage including articular, nasal, auricular, tracheal/bronchial, and intervertebral disc fibrocartilage. Manuscripts on clinical and laboratory research are welcome. Review articles, editorials, and letters are also encouraged. The ICRS envisages CARTILAGE as a forum for the exchange of knowledge among clinicians, scientists, patients, and researchers. The International Cartilage Repair Society (ICRS) is dedicated to promotion, encouragement, and distribution of fundamental and applied research of cartilage in order to permit a better knowledge of function and dysfunction of articular cartilage and its repair.