Although inflammation is necessary during the early phases of tissue repair, persistent inflammation contributes to fibrosis. Acute tendon injuries often heal through a fibrotic mechanism, which impedes regeneration and functional recovery. Because inflammation mediated by nuclear factor κB (NF-κB) signaling is implicated in this process, we examined the spatial, temporal, and cell type–specific activation profile of canonical NF-κB signaling during tendon healing. NF-κB signaling was maintained through all phases of tendon healing in mice, including the remodeling phase, and tenocytes and myofibroblasts from the Scleraxis (Scx) lineage were the predominant populations that retained NF-κB activation into the late stages of repair. We confirmed persistent NF-κB activation in myofibroblasts in human tendon scar tissue. Deleting the canonical NF-κB kinase, IKKβ, in Scx-lineage cells in mice increased apoptosis and the deposition of the matrix protein periostin during the late stages of tendon repair, suggesting that persistent NF-κB signaling may facilitate myofibroblast survival and fibrotic progression. Consistent with this, myofibroblasts in human tendon scar samples displayed enhanced prosurvival signaling compared to control tissue. Together, these data suggest that NF-κB may contribute to fibrotic tendon healing through both inflammation-dependent and inflammation-independent functions, such as NF-κB–mediated cell survival.

尽管炎症在组织修复的早期阶段是必需的，但持续的炎症会导致纤维化。急性肌腱损伤通常通过纤维化机制愈合，这阻碍了再生和功能恢复。因为由核因子 κB (NF-κB) 信号传导介导的炎症与该过程有关，我们检查了肌腱愈合过程中典型 NF-κB 信号传导的空间、时间和细胞类型特异性激活特征。NF-κB 信号在小鼠肌腱愈合的所有阶段都得到维持，包括重塑阶段，以及来自巩膜轴的肌腱细胞和肌成纤维细胞( Scx) 谱系是将 NF-κB 激活保留到修复后期的主要群体。我们证实了人肌腱瘢痕组织中肌成纤维细胞的持续 NF-κB 激活。在小鼠的 Scx谱系细胞中删除典型的 NF-κB 激酶 IKKβ会增加细胞凋亡和肌腱修复后期基质蛋白骨膜蛋白的沉积，这表明持续的 NF-κB 信号传导可能促进肌成纤维细胞的存活和纤维化进展。与此一致，与对照组织相比，人肌腱疤痕样本中的肌成纤维细胞显示出增强的促存活信号。总之，这些数据表明 NF-κB 可能通过炎症依赖性和非炎症依赖性功能促进纤维化肌腱愈合，例如 NF-κB 介导的细胞存活。