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<p>Rheumatoid arthritis (RA) is a systemic immune-mediated synovial disorder characterized by chronic inflammation in the joints, resulting in heightened bone resorption and physical disabilities. RA develops through a complex interaction of different cellular and molecular factors. Fibroblast-like synoviocytes (FLSs), which have a significant role in the pathophysiology of RA, exhibiting an aggressive and inflammatory phenotype that leads to increased osteoclastogenesis and joint destruction. Understanding the cell-to-cell communication between osteoclasts and FLSs is essential for elucidating the pathophysiology of RA and identifying potential therapeutic targets for retrieving joint integrity and function. In this review, by studying the interactions of FLS and osteoclast in the inflammatory process of the disease, the ERK and PI3K/Akt pathways were found as common points in the activation of FLSs and osteoclastogenesis, which can be introduced as potential therapeutic targets in the experimental researches aimed at reducing bone destruction.</p>

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Deciphering the role of ERK and PI3K/Akt as crosstalk pathways between fibroblast-like synoviocytes and osteoclasts; novel therapeutic approach for rheumatoid arthritis

  • 期刊论文

  • 发表日期：

    2025年7月1日

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  • Seyede-Sara Hassani,
  • Elham Farhadi,
  • Seyed-Alireza Esmaeili,
  • Mahdi Mahmoudi,
  • Mahmoud Mahmoudi,
  • Jalil Tavakol Afshari,
  • Masoumeh Akhlaghi,
  • Ahmadreza Jamshidi

摘要

Rheumatoid arthritis (RA) is a systemic immune-mediated synovial disorder characterized by chronic inflammation in the joints, resulting in heightened bone resorption and physical disabilities. RA develops through a complex interaction of different cellular and molecular factors. Fibroblast-like synoviocytes (FLSs), which have a significant role in the pathophysiology of RA, exhibiting an aggressive and inflammatory phenotype that leads to increased osteoclastogenesis and joint destruction. Understanding the cell-to-cell communication between osteoclasts and FLSs is essential for elucidating the pathophysiology of RA and identifying potential therapeutic targets for retrieving joint integrity and function. In this review, by studying the interactions of FLS and osteoclast in the inflammatory process of the disease, the ERK and PI3K/Akt pathways were found as common points in the activation of FLSs and osteoclastogenesis, which can be introduced as potential therapeutic targets in the experimental researches aimed at reducing bone destruction.