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Review
. 2025 Jul 1;52(1):662.
doi: 10.1007/s11033-025-10769-9.

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

Seyede-Sara Hassani  1   2 , Elham Farhadi  3   4 , Seyed-Alireza Esmaeili  5   6 , Mahdi Mahmoudi  1   7 , Mahmoud Mahmoudi  2   8 , Jalil Tavakol Afshari  2   8 , Masoumeh Akhlaghi  1   7 , Ahmadreza Jamshidi  1
Affiliations
Review

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

Seyede-Sara Hassani et al. Mol Biol Rep. .

Abstract

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.

Keywords: ERK; Fibroblast-like synoviocyte; Osteoclast; PI3K/Akt; Rheumatoid arthritis.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

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References

    1. Nygaard G, Firestein GS (2020) Restoring synovial homeostasis in rheumatoid arthritis by targeting fibroblast-like synoviocytes. Nat Rev Rheumatol 16(6):316–333 - PubMed - PMC - DOI
    1. Iwamoto N, Kawakami A (2022) The monocyte-to-osteoclast transition in rheumatoid arthritis: recent findings. Front Immunol 13:998554 - PubMed - PMC - DOI
    1. Wehmeyer C, Pap T, Buckley CD, Naylor AJ (2017) The role of stromal cells in inflammatory bone loss. Clin Experimental Immunol 189(1):1–11 - DOI
    1. Firestein GS, McInnes IB (2017) Immunopathogenesis of rheumatoid arthritis. Immunity 46(2):183–196 - PubMed - PMC - DOI
    1. Falconer J, Murphy AN, Young SP, Clark AR, Tiziani S, Guma M et al (2018) Synovial cell metabolism and chronic inflammation in rheumatoid arthritis. Arthritis Rheumatol 70(7):984–999 - PubMed - PMC - DOI

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