CTRP3 exacerbates tendinopathy by dysregulating tendon stem cell differentiation and altering extracellular matrix composition

作者：Yong-Sik Cho, Hyeon-Seop Kim, Hyeon-Seop Kim, Donghyun Kang, Hyeonkyeong Kim, Hyeonkyeong Kim, Narae Lee, Jihye Yun, Yi‐Jun Kim, Kyoung Min Lee, Jin‐Hee Kim, Jin‐Hee Kim, Hang‐Rae Kim, Hang‐Rae Kim, Young‐il Hwang, Chris Hyunchul Jo, Jin-Hong Kim, Jin-Hong Kim · 发表于：Science Advances · 年份：2021 · DOI：10.1126/sciadv.abg6069 · 被引用次数：57 · 研究领域：Tendon Structure and Treatment、Shoulder Injury and Treatment、Veterinary Equine Medical Research

Tendinopathy, the most common disorder affecting tendons, is characterized by chronic disorganization of the tendon matrix, which leads to tendon tear and rupture. The goal was to identify a rational molecular target whose blockade can serve as a potential therapeutic intervention for tendinopathy. We identified C1q/TNF-related protein-3 (CTRP3) as a markedly up-regulated cytokine in human and rodent tendinopathy. Overexpression of CTRP3 enhanced the progression of tendinopathy by accumulating cartilaginous proteoglycans and degenerating collagenous fibers in the mouse tendon, whereas CTRP3 knockdown suppressed the tendinopathy pathogenesis. Functional blockade of CTRP3 using a neutralizing antibody ameliorated overuse-induced tendinopathy of the Achilles and rotator cuff tendons. Mechanistically, CTRP3 elicited a transcriptomic pattern that stimulates abnormal differentiation of tendon stem/progenitor cells and ectopic chondrification as an effect linked to activation of Akt signaling. Collectively, we reveal an essential role for CTRP3 in tendinopathy and propose a potential therapeutic strategy for the treatment of tendinopathy.