1. Figure 3 Inflammatory mechanisms in tendinopathy
Figure 3 | Inflammatory mechanisms in tendinopathy. This figure highlights the potential targetable intracellular signalling pathways that have functional consequences (such as regulation of extracellular matrix (ECM), immune cell recruitment and cell proliferation) relevant to tendon pathology. For example, activation of mitogen-activated protein kinase (MAPK) signalling by the cytokines IL-33 (through myeloid differentiation primary response protein MyD88, IL-1 receptor-associated kinase (IRAK) and TNF receptor-associated factor 6 (TRAF6)), IL-6 (through p130) and IL-17 (through TRAF6); activation of nuclear factor κB (NF-κB) signalling by TNF (through TRAF2) or 15-epi-lipoxin A4 (15-epi-LXA4); and activation Janus kinase (JAK) and signal transducer and activator of transcription (STAT) by IL-13 result in downstream mediation of enhanced cytokine and chemokine production, ECM remodelling (collagen and other proteins), proliferation and angiogenesis, all of which become dysregulated in tendon disease. Appreciation of these pathways could help define the molecular checkpoints that modify a homeostatic inflammatory response toward an aberrant inflammatory tendon microenvironment that leads to clinical tendinopathy. An ideal tendinopathy target should modify the proinflammatory response and promote resolution by sparing inflammation-induced healing moieties and encouraging robust and rapid matrix repair. COX, cyclooxygenase; EP, prostaglandin E2 receptor; FPR2, N-formyl peptide receptor 2; PGE2, prostaglandin E2.
Millar, N. L. et al. (2017) Inflammatory mechanisms in tendinopathy – towards translation
Nat. Rev. Rheumatol. doi: /nrrheum