Metformin limits osteoarthritis development and progression through activation of AMPK signalling.

Annals of the Rheumatic Diseases
Jun LiDi Chen

Abstract

In this study, we aim to determine the effect of metformin on osteoarthritis (OA) development and progression. Destabilisation of the medial meniscus (DMM) surgery was performed in 10-week-old wild type and AMP-activated protein kinase (AMPK)α1 knockout (KO) mice. Metformin (4 mg/day in drinking water) was given, commencing either 2 weeks before or 2 weeks after DMM surgery. Mice were sacrificed 6 and 12 weeks after DMM surgery. OA phenotype was analysed by micro-computerised tomography (μCT), histology and pain-related behaviour tests. AMPKα1 (catalytic alpha subunit of AMPK) expression was examined by immunohistochemistry and immunofluorescence analyses. The OA phenotype was also determined by μCT and MRI in non-human primates. Metformin upregulated phosphorylated and total AMPK expression in articular cartilage tissue. Mild and more severe cartilage degeneration was observed at 6 and 12 weeks after DMM surgery, evidenced by markedly increased Osteoarthritis Research Society International scores, as well as reduced cartilage areas. The administration of metformin, commencing either before or after DMM surgery, caused significant reduction in cartilage degradation. Prominent synovial hyperplasia and osteophyte formation were o...Continue Reading

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Citations

Sep 10, 2020·Pharmaceuticals·Teresa SalvatoreFerdinando Carlo Sasso
Jan 1, 2021·Ageing Research Reviews·Linli ZhengAli Mobasheri
Nov 27, 2020·Osteoarthritis and Cartilage·M H J van den Bosch
Nov 19, 2020·Pharmacological Reviews·Muhammad Saad YousufTheodore J Price
May 4, 2021·Frontiers in Pharmacology·Xiaoyan CaiChanghai Ding
Jul 10, 2021·Frontiers in Cell and Developmental Biology·Dan YiDi Chen
Aug 28, 2021·Life·Shenglan Wang, Yi Dai
Oct 9, 2021·Arthritis Research & Therapy·Dennis M MintonAdam R Konopka

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