Inhibition of a Signaling Modality Within the Gp130 Receptor Enhances Tissue Regeneration and Mitigates Osteoarthritis

    March 2023 in “ Science Translational Medicine
    Ruzanna Shkhyan, Candace Flynn, Emma Lamoure, Arijita Sarkar, Benjamin Van Handel, Jinxiu Li, Jesse York, Nicholas W. Banks, Robert Van der Horst, Nancy Q. Liu, Siyoung Lee, Paul Bajaj, Kanagasabai Vadivel, Hans I.Chen Harn, Jade Tassey, Thomas P. Lozito, Jay R. Lieberman, Cheng Ming Chuong, Mark Hurtig, Denis Evseenko
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    TLDR Blocking a certain signal in the gp130 receptor can improve tissue healing and lessen osteoarthritis symptoms.
    The study identified a cellular stress sensor, a tyrosine residue at position 814 (Y814) of glycoprotein 130 (gp130), responsible for inflammatory responses. By replacing the tyrosine with a phenylalanine (F814), researchers observed a decrease in pro-inflammatory and pro-fibrotic signaling cascades after stimulation in vitro. Mice with the F814 modification showed increased resistance to osteoarthritis and enhanced skin regeneration after wounding. A small molecule that modulated gp130 receptor pro-inflammatory signaling also improved osteoarthritis symptoms in rodents and dogs. These findings suggest that targeting Y814 in gp130 could potentially enhance tissue regeneration and mitigate osteoarthritis.
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