ArticleExperimental & molecular medicine2024
Advanced glycation end products promote meniscal calcification by activating the mTOR-ATF4 positive feedback loop.
Article in Experimental & molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
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- Elucidating the Role of Oxidative Stress-Associated Genes FKBP Prolyl Isomerase 5 in Osteoarthritis Development and Immunological Milieu.Biological procedures online · 2026Article
- Integrated Transcriptomics and Metabolomics with Machine Learning Identify Flavonoids as Key Effectors in Wheat Root Thermotolerance.Plants (Basel, Switzerland) · 2026Article
- Targeting post-translational modifications: novel insights into bone metabolic diseases.Journal of advanced research · 2026Review
- Amino Acid Metabolism in Chronic Liver Disease: from Pathogenic Driver to Therapeutic Target.International journal of biological sciences · 2026Review
- Exosome-loaded tannic acid-thioctic acid hydrogel enhances wound healing in coagulation disorders.Materials today. Bio · 2025Article
- MAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Molecular Mechanism Investigation of HBP-A Slows Down Meniscus Hypertrophy and Mineralisation by the Damage Mechanical Model.Journal of cellular and molecular medicine · 2024Article
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Authors and funding
14 authors at 7 institutions in 1 country.
Funding
Abstract
The meniscus is vital for maintaining knee homeostasis and function. Meniscal calcification is one of the earliest radiological indicators of knee osteoarthritis (KOA), and meniscal calcification is associated with alterations in biomechanical properties. Meniscal calcification originates from a biochemical process similar to vascular calcification. Advanced glycation end products (AGEs) and their receptors (RAGEs) reportedly play critical roles in vascular calcification. Herein, we investigated whether targeting AGE-RAGE is a potential treatment for meniscal calcification. In our study, we demonstrated that AGE-RAGE promotes the osteogenesis of meniscal cells and exacerbates meniscal calcification. Mechanistically, AGE-RAGE activates mTOR and simultaneously promotes ATF4 accumulation, thereby facilitating the ATF4-mTOR positive feedback loop that enhances the osteogenic capacity of meniscal cells. In this regard, mTOR inhibits ATF4 degradation by reducing its ubiquitination, while ATF4 activates mTOR by increasing arginine uptake. Our findings substantiate the unique role of AGE-RAGE in the meniscus and reveal the role of the ATF4-mTOR positive feedback loop during the osteogenesis of meniscal cells; these results provide potential therapeutic targets for KOA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.