Effects of metformin on knee joint capsule fibrosis in a diabetic mouse model.

IF 4.7 2区 医学 Q2 CELL & TISSUE ENGINEERING Bone & Joint Research Pub Date : 2024-07-03 DOI:10.1302/2046-3758.137.BJR-2023-0384.R1
Toichiro Naito, Yoshiaki Yamanaka, Kotaro Tokuda, Naohito Sato, Takafumi Tajima, Manabu Tsukamoto, Hitoshi Suzuki, Makoto Kawasaki, Eiichiro Nakamura, Akinori Sakai
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Abstract

Aims: The antidiabetic agent metformin inhibits fibrosis in various organs. This study aims to elucidate the effects of hyperglycaemia and metformin on knee joint capsule fibrosis in mice.

Methods: Eight-week-old wild-type (WT) and type 2 diabetic (db/db) mice were divided into four groups without or with metformin treatment (WT met(-/+), Db met(-/+)). Mice received daily intraperitoneal administration of metformin and were killed at 12 and 14 weeks of age. Fibrosis morphology and its related genes and proteins were evaluated. Fibroblasts were extracted from the capsules of 14-week-old mice, and the expression of fibrosis-related genes in response to glucose and metformin was evaluated in vitro.

Results: The expression of all fibrosis-related genes was higher in Db met(-) than in WT met(-) and was suppressed by metformin. Increased levels of fibrosis-related genes, posterior capsule thickness, and collagen density were observed in the capsules of db/db mice compared with those in WT mice; these effects were suppressed by metformin. Glucose addition increased fibrosis-related gene expression in both groups of mice in vitro. When glucose was added, metformin inhibited the expression of fibrosis-related genes other than cellular communication network factor 2 (Ccn2) in WT mouse cells.

Conclusion: Hyperglycaemia promotes fibrosis in the mouse knee joint capsule, which is inhibited by metformin. These findings can help inform the development of novel strategies for treating knee joint capsule fibrosis.

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二甲双胍对糖尿病小鼠模型膝关节囊纤维化的影响
目的:抗糖尿病药物二甲双胍可抑制多种器官的纤维化。本研究旨在阐明高血糖和二甲双胍对小鼠膝关节囊纤维化的影响:方法:将八周大的野生型(WT)和 2 型糖尿病(db/db)小鼠分为四组,分别给予二甲双胍治疗(WT met(-/+)、Db met(-/+))或不给予二甲双胍治疗(WT met(-/+)、Db met(-/+))。小鼠每天腹腔注射二甲双胍,分别于12周龄和14周龄处死。对纤维化形态及其相关基因和蛋白质进行了评估。从14周龄小鼠的蒴果中提取成纤维细胞,在体外评估纤维化相关基因对葡萄糖和二甲双胍的表达:结果:所有纤维化相关基因在Db met(-)中的表达均高于WT met(-),且二甲双胍抑制了其表达。与 WT 小鼠相比,在 db/db 小鼠的囊中观察到纤维化相关基因水平、后囊厚度和胶原密度增加;二甲双胍抑制了这些影响。添加葡萄糖会增加两组小鼠体外纤维化相关基因的表达。加入葡萄糖后,二甲双胍抑制了WT小鼠细胞中除细胞通讯网络因子2(Ccn2)以外的纤维化相关基因的表达:结论:高血糖会促进小鼠膝关节囊纤维化,而二甲双胍能抑制这种纤维化。这些发现有助于开发治疗膝关节囊纤维化的新策略。
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来源期刊
Bone & Joint Research
Bone & Joint Research CELL & TISSUE ENGINEERING-ORTHOPEDICS
CiteScore
7.40
自引率
23.90%
发文量
156
审稿时长
12 weeks
期刊介绍: The gold open access journal for the musculoskeletal sciences. Included in PubMed and available in PubMed Central.
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