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Metformin regulates chondrocyte senescence and proliferation through microRNA-34a/SIRT1 pathway in osteoarthritis

Overview of attention for article published in Journal of Orthopaedic Surgery and Research, March 2023
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Title
Metformin regulates chondrocyte senescence and proliferation through microRNA-34a/SIRT1 pathway in osteoarthritis
Published in
Journal of Orthopaedic Surgery and Research, March 2023
DOI 10.1186/s13018-023-03571-5
Pubmed ID
Authors

Shiju Yan, Wenjing Dong, Zhirui Li, Junqiang Wei, Tao Han, Junliang Wang, Feng Lin

Abstract

Osteoarthritis (OA) is the most common degenerative disease in joints among elderly patients. Senescence is deeply involved in the pathogenesis of osteoarthritis. Metformin is widely used as the first-line drug for Type 2 diabetes mellitus (T2DM), and has great potential for the treatment of other aging-related disorders, including OA. However, the role of metformin in OA is not fully elucidated. Therefore, our aim here was to investigate the effects of metformin on human chondrocytes. After metformin treatment, expression level of microRNA-34a and SIRT1 in chondrocyte were detected with quantitative real-time PCR and immunofluorescence staining. Then, microRNA-34a mimic and small interfering RNA (siRNA) against SIRT1 (siRNA-SIRT1) were transfected into chondrocyte. Senescence-associated β-galactosidase (SA-β-gal) staining was performed to assess chondrocyte senescence. Chondrocyte viability was illustrated with MTT and colony formation assays. Western blot was conducted to detect the expression of P16, IL-6, matrix metalloproteinase-13 (MMP-13), Collagen type II (COL2A1) and Aggrecan (ACAN). We found that metformin treatment (1 mM) inhibited microRNA-34a while promoted SIRT1 expression in OA chondrocytes. Both miR-34a mimics and siRNA against SIRT1 inhibited SIRT1 expression in chondrocytes. SA-β-gal staining assay confirmed that metformin reduced SA-β-gal-positive rate of chondrocytes, while transfection with miR-34a mimics or siRNA-SIRT1 reversed it. MTT assay and colony formation assay showed that metformin accelerated chondrocyte proliferation, while miR-34a mimics or siRNA-SIRT1 weakened this effect. Furthermore, results from western blot demonstrated that metformin suppressed expression of senescence-associated protein P16, proinflammatory cytokine IL-6 and catabolic gene MMP-13 while elevated expression of anabolic proteins such as Collagen type II and Aggrecan, which could be attenuated by transfection with miR-34a mimics. Overall, our data suggest that metformin regulates chondrocyte senescence and proliferation through microRNA-34a/SIRT1 pathway, indicating it could be a novel strategy for OA treatment.

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The data shown below were collected from the profiles of 3 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 6 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 6 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 2 33%
Student > Bachelor 2 33%
Student > Master 1 17%
Unknown 1 17%
Readers by discipline Count As %
Unspecified 2 33%
Pharmacology, Toxicology and Pharmaceutical Science 1 17%
Medicine and Dentistry 1 17%
Engineering 1 17%
Unknown 1 17%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 July 2023.
All research outputs
#17,165,923
of 25,218,929 outputs
Outputs from Journal of Orthopaedic Surgery and Research
#765
of 1,606 outputs
Outputs of similar age
#243,804
of 416,364 outputs
Outputs of similar age from Journal of Orthopaedic Surgery and Research
#21
of 63 outputs
Altmetric has tracked 25,218,929 research outputs across all sources so far. This one is in the 21st percentile – i.e., 21% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,606 research outputs from this source. They receive a mean Attention Score of 4.3. This one is in the 33rd percentile – i.e., 33% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 416,364 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 29th percentile – i.e., 29% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 63 others from the same source and published within six weeks on either side of this one. This one is in the 42nd percentile – i.e., 42% of its contemporaries scored the same or lower than it.