Department of Orthopedics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Key Laboratory of Protein and Peptide Pharmaceutical, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; Nanozyme Laboratory in Zhongyuan, Henan Academy of Innovations in Medical Science, Zhengzhou, Henan 451163, China.
Int Immunopharmacol. 2024 Aug 20;137:112528. doi: 10.1016/j.intimp.2024.112528. Epub 2024 Jun 21.
Low back pain due to epidural fibrosis is a major complication after spine surgery. Macrophages infiltrate the wound area post laminectomy, but the role of macrophages in epidural fibrosis remains largely elusive. In a mouse model of laminectomy, macrophage depletion decreased epidural fibrosis. CD146, an adhesion molecule involved in cell migration, is expressed by macrophages. CD146-defective macrophages exhibited impaired migration, which was mediated by reduced expression of CCR2 and suppression of the MAPK/ERK signaling pathway. CD146-defective macrophages suppress the MAPK/ERK signaling pathway by increasing Erdr1. In vivo, CD146 deficiency decreased macrophage infiltration and reduced extracellular matrix deposition in wound tissues. Moreover, the anti-CD146 antibody AA98 suppressed macrophage infiltration and epidural fibrosis. Taken together, these findings demonstrated that CD146 deficiency alleviates epidural fibrosis by decreasing the migration of macrophages via the Erdr1/ERK/CCR2 pathway. Blocking CD146 and macrophage infiltration may help alleviate epidural fibrosis.
由于硬膜外纤维化导致的下腰痛是脊柱手术后的主要并发症。巨噬细胞在椎板切除术后浸润伤口区域，但巨噬细胞在硬膜外纤维化中的作用在很大程度上仍不清楚。在椎板切除术的小鼠模型中，巨噬细胞耗竭可减少硬膜外纤维化。CD146 是一种参与细胞迁移的黏附分子，在巨噬细胞中表达。CD146 缺陷型巨噬细胞表现出迁移受损，这是由 CCR2 表达减少和 MAPK/ERK 信号通路抑制介导的。CD146 缺陷型巨噬细胞通过增加 Erdr1 来抑制 MAPK/ERK 信号通路。在体内，CD146 缺乏可减少巨噬细胞浸润并减少伤口组织中的细胞外基质沉积。此外，抗 CD146 抗体 AA98 可抑制巨噬细胞浸润和硬膜外纤维化。总之，这些发现表明，CD146 缺乏通过 Erdr1/ERK/CCR2 途径减少巨噬细胞迁移来缓解硬膜外纤维化。阻断 CD146 和巨噬细胞浸润可能有助于缓解硬膜外纤维化。
