Targeting the IL-17A pathway for therapy in early-stage tendinopathy.

• Tác giả: Nathalie Accart, Moeed Akbar, Nicolau Beckmann, Christian Bruns, Claudio Calonder, Michaela Kneissel, Frank Kolbinger, Olivier Leupin, Yufei Li, Iain B McInnes, Neal L Millar, Friedrich Raulf, Matthias Schieker, Richard M Siegel, Eckhard Weber
• Ngôn ngữ: eng
• Ký hiệu phân loại: 809.008 History and description with respect to kinds of persons
• Thông tin xuất bản: England : RMD open , 2025
• Bộ sưu tập: NCBI
• ID: 644071

Tóm tắt

OBJECTIVES: Tendinopathy is a frequent clinical problem and represents an extraordinary health economic and socioeconomic burden with high unmet medical needs. Recent clinical evidence suggests blockade of interleukin 17A (IL-17A) for tendinopathy therapy. The present preclinical study elucidates the biological mechanisms of IL-17A pathway stimulation and blockade in tendinopathy. METHODS: We explored whether IL-17A and other IL-17 family members are differentially expressed in biopsies of healthy, early-stage and late-stage tendinopathic human rotator cuff tendons using RT-qPCR. IL-17 pathway signature genes in healthy human tendon-derived cells were identified following IL-17A stimulation using AmpliSeq RNA. The molecular, structural and functional consequences of IL-17A pathway stimulation were explored in healthy human tendon-derived cells and in a rat tendon fascicle model ex vivo. The effects of IL-17A pathway blockade were investigated in a rat model of rotator cuff tendinopathy in vivo. RESULTS: We provide evidence of differential expression of IL-17A mRNA ( CONCLUSION: Our data provide evidence that IL-17A is a key contributor to the pathogenesis of tendinopathy by promoting tendon inflammation and degeneration and that IL-17A blockade may represent a potential therapy in early-stage tendinopathy.