AI Article Synopsis

  • The study investigates how hyperglycemia (high blood sugar) and the antidiabetic drug metformin affect fibrosis (thickening and scarring) in the knee joint capsules of mice.
  • Researchers used two types of mice: normal (wild-type) and diabetic (db/db), with some receiving metformin treatment, and evaluated various fibrosis-related genes and proteins.
  • Results showed metformin reduced fibrosis-related gene expression and physical signs of fibrosis (like increased capsule thickness) in diabetic mice, suggesting it could be a potential treatment for knee joint capsule fibrosis linked to high blood sugar levels.

Article 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 () 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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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11219202PMC
http://dx.doi.org/10.1302/2046-3758.137.BJR-2023-0384.R1DOI Listing

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