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

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.