Adipokine Contribution to the Pathogenesis of Osteoarthritis

Figure 2

Leptin signal transduction. The Ob receptor b (ObR b) isoform of leptin binds to the JAK-STAT intracellular signaling system. As a consequence of leptin binding to its receptor, JAK2 is activated by the autophosphorylation. STAT1 and STAT5 bind tyrosine residues. STAT3 proteins form dimers and translocate to the nucleus and regulate c-fos, c-jun, SOCS3, and AP1 gene expression. Src homology domains of receptor (SHP2) activate MAPK pathways (p38, p42/44, and ERK1/2). These pathways induce the expression of cytokine and chemokine genes. Moreover, ObRb/leptin also induces the transcription of metalloproteinases and aggrecanases, cartilage degradation proteins, and the signaling pathways of inflammatory cytokines through activation of NF-kB and AP-1 that transcribe the genes of inflammatory proteins (IL-1β, IL-6, TNF-α, and induced nitric oxide synthase among others). Leptin, through interleukin 6 (IL-6)/gp130 pathway activates STAT3, which in the nucleus, transcribes the gene of SOCS3 that suppresses the leptin signaling pathways. Bcl: B cell lymphoma; ERK: extracellular signal-regulated kinase; JAK: c-Jun N-terminal kinase-associated kinase; MAPK: mitogen-activated protein kinase; NF-kB: nuclear factor-kappa B; ObR: Ob receptor; SOCS3: suppressor of cytokine signaling-3; STAT: signal transducer and activator of transcription.