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从莓鲨软骨中分离出的蛋白聚糖显示出潜在的抗骨关节炎特性。

Proteoglycans isolated from the bramble shark cartilage show potential anti-osteoarthritic properties.

机构信息

Biochemistry and Nutrition Division, ICAR-Central Institute of Fisheries Technology, Kochi, Kerala, India.

Peninsular and Marine Fish Genetic Resources Centre, ICAR-National Bureau of Fish Genetic Resources, CMFRI Campus, Kochi, Kerala, India.

出版信息

Inflammopharmacology. 2019 Feb;27(1):175-187. doi: 10.1007/s10787-018-00554-5. Epub 2019 Jan 1.

Abstract

Osteoarthritis (OA) causes articular cartilage destruction, initiating pain and inflammation in the joints, resulting in joint disability. Medications are available to manage these symptoms; however, their effects on the disease progression are limited. Loss of proteoglycans (PGs) was reported to contribute articular cartilage destruction in OA. Therapeutics approaches were previously studied in the animal models of OA. In the present study, we investigated the oral efficacy of four dosages of PGs (25 mg/kg, 50 mg/kg, 100 mg/kg and 200 mg/kg), isolated from the bramble shark cartilage, in an animal model of OA. Indomethacin was used as a bioequivalent formulation. Primarily, the mass spectrum analysis of the purified PGs obtained from bramble shark cartilage revealed the presence of two unique peptides including AGWLSDGSVR and LDGNPINLSK, that showed sequence similarity with aggrecan core-protein and epiphycan, respectively. The levels of C-reactive protein and uric acid in the OA rats were reduced when treated with PGs. Histopathology analysis displayed less cartilage erosion and neovascularization in OA rats treated with PGs. The X-ray imaging presented higher bone density with 200 mg/kg dosage of PG treatment in OA rats. The expressions of the inflammatory modulators including TNF-α, IL-1β, MMP13, NOS2, IL-10 and COX-2 were found to be moderated with PG treatment. In addition, PG treatment maintained the activities of antioxidant enzymes, including SOD and catalase in the joint tissues with a higher GSH content, in a dose-dependent manner. Taken together, our preliminary findings report the anti-osteoarthritic properties of PGs and recommend to evaluate its efficacy and safety in randomized trials.

摘要

骨关节炎(OA)导致关节软骨破坏,引发关节疼痛和炎症,导致关节功能障碍。有药物可用于治疗这些症状;然而,它们对疾病进展的影响是有限的。据报道,蛋白聚糖(PGs)的丧失导致 OA 中的关节软骨破坏。以前在 OA 的动物模型中研究了治疗方法。在本研究中,我们研究了从荆棘鲨鱼软骨中分离的四种剂量 PGs(25mg/kg、50mg/kg、100mg/kg 和 200mg/kg)在 OA 动物模型中的口服疗效。吲哚美辛用作生物等效制剂。首先,从荆棘鲨鱼软骨中获得的纯化 PGs 的质谱分析表明存在两种独特的肽,包括 AGWLSDGSVR 和 LDGNPINLSK,分别与聚集蛋白核心蛋白和外胚层蛋白表现出序列相似性。OA 大鼠用 PG 治疗后,C-反应蛋白和尿酸水平降低。组织病理学分析显示,OA 大鼠用 PG 治疗后软骨侵蚀和新血管形成减少。X 射线成像显示,OA 大鼠用 200mg/kg 剂量 PG 治疗后骨密度更高。PG 治疗可调节炎症调节剂的表达,包括 TNF-α、IL-1β、MMP13、NOS2、IL-10 和 COX-2。此外,PG 治疗以剂量依赖性方式维持关节组织中抗氧化酶(包括 SOD 和过氧化氢酶)的活性,并保持较高的 GSH 含量。总之,我们的初步研究结果报告了 PGs 的抗骨关节炎特性,并建议在随机试验中评估其疗效和安全性。

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