Fig. 5.

Feed-forward pathogenesis of OA relying on chondrocytic inflammatory signaling, which results in Piezo1 increased function. A schematic of our findings and proposed OA pathogenetic mechanism. Signaling hubs and their consequences, upon activation as we demonstrate, are shown as a sequence 1 to 6. Shown in black letters, 1 to 6 is supported by our findings and known background. We interpret the result as “hypermechanotransduction & increased cellular damage,” in purple and speculate, in blue, that a loosened/rarefied F-actin may enhance p38 phosphorylation by making p38 more available for kinases.