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. 2021 Aug 26;22(17):9208. doi: 10.3390/ijms22179208

Figure 4.

Figure 4

Schematic representation of IL-6 function in osteoarthritis pathogenesis. IL-6 acts by binding membrane-bound IL-6R or sIL-6R that associates with gp130. Gp130 initiates intracellular signaling that regulates the inflammation and expression of enzymes, collagen and proteoglycans. sIL-6R is produced by means of alternative splicing or the shedding of membrane-bound IL-6R. sgp130 can inhibit IL-6 signaling. Through classic and trans-signaling, IL-6 activates the PI3K, JAK/STAT and MAPK signaling pathways that regulate enzymes production (TIMP, MMPs and ADAMTS) and type II collagen and proteoglycan synthesis. Thus, IL-6 balances between anti-inflammatory and proinflammatory effects, but the latter predominates, ultimately leading to the progression of osteoarthritis. ADAM—a disintegrin and metalloproteinase; ADAMTS—a disintegrin-like and metalloproteinase with thrombospondin motifs; gp130—glycoprotein 130; IL-6—interleukin-6; MMP—matrix metalloproteinases; sgp130—soluble glycoprotein 130; sIL-6R—soluble IL-6 receptor; TIMP—tissue inhibitor of metalloproteinase; JAK/STAT—Janus kinase/signal transducers and activators of transcription; PI3K—phosphoinositide 3-kinases; MAPK—mitogen-activated protein kinase.