Department of Orthopaedics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
FASEB J. 2021 Jun;35(6):e21618. doi: 10.1096/fj.202100049R.
Tendons are dense connective tissues that transmit muscle forces to the skeleton. After adult injury, healing potential is generally poor and dominated by scar formation. Although the immune response is a key feature of healing, the specific immune cells and signals that drive tendon healing have not been fully defined. In particular, the immune regulators underlying tendon regeneration are almost completely unknown due to a paucity of tendon regeneration models. Using a mouse model of neonatal tendon regeneration, we screened for immune-related markers and identified upregulation of several genes associated with inflammation, macrophage chemotaxis, and TGFβ signaling after injury. Depletion of macrophages using AP20187 treatment of MaFIA mice resulted in impaired functional healing, reduced cell proliferation, reduced ScxGFP+ neo-tendon formation, and altered tendon gene expression. Collectively, these results show that inflammation is a key component of neonatal tendon regeneration and demonstrate a requirement for macrophages in effective functional healing.
肌腱是一种密集的结缔组织，将肌肉力量传递到骨骼。在成人受伤后，愈合潜力通常较差，主要形成疤痕。尽管免疫反应是愈合的一个关键特征，但驱动肌腱愈合的特定免疫细胞和信号尚未完全确定。特别是，由于缺乏肌腱再生模型，肌腱再生的免疫调节剂几乎完全未知。使用新生鼠肌腱再生模型，我们筛选了与免疫相关的标记物，并在损伤后发现了几个与炎症、巨噬细胞趋化和 TGFβ 信号相关的基因上调。使用 MaFIA 小鼠的 AP20187 处理耗尽巨噬细胞导致功能愈合受损、细胞增殖减少、ScxGFP+ 新生肌腱形成减少以及肌腱基因表达改变。总的来说，这些结果表明炎症是新生儿肌腱再生的关键组成部分，并证明了巨噬细胞在有效功能愈合中的必要性。
