CD146-dependent macrophage infiltration promotes epidural fibrosis via the Erdr1/ERK/CCR2 pathway
Jinpeng Sun1, Mohan Shi1, Zeyuan Song1
1Department of Orthopedics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
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.
Insights
Blocking CD146 reduces macrophage migration, alleviating epidural fibrosis after spine surgery. This study reveals CD146
Area of Science:
- Immunology and Cell Biology
- Spinal Surgery Complications
Background:
- Epidural fibrosis is a significant complication following spine surgery, often leading to low back pain.
- The precise role of macrophages in the development of epidural fibrosis post-laminectomy has been unclear.
Purpose of the Study:
- To investigate the role of the adhesion molecule CD146 in macrophage-mediated epidural fibrosis.
- To explore the molecular mechanisms by which CD146 influences macrophage migration and fibrosis development.
Main Methods:
- Utilized a mouse model of laminectomy to study epidural fibrosis.
- Employed macrophage depletion strategies and CD146-defective macrophages.
- Analyzed cell migration, signaling pathways (MAPK/ERK), gene expression (Erdr1, CCR2), and extracellular matrix deposition.
Main Results:
- Macrophage depletion significantly decreased epidural fibrosis in the laminectomy model.
- CD146 deficiency in macrophages impaired their migration, linked to reduced CCR2 expression and MAPK/ERK pathway suppression via increased Erdr1.
- In vivo, CD146 deficiency and anti-CD146 antibody treatment reduced macrophage infiltration and extracellular matrix deposition, thereby suppressing epidural fibrosis.
Conclusions:
- CD146 plays a critical role in macrophage migration contributing to epidural fibrosis.
- Targeting CD146 and subsequent macrophage infiltration offers a potential therapeutic strategy for mitigating post-surgical epidural fibrosis.
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