Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2021 Jun 8;12:666361. doi: 10.3389/fimmu.2021.666361. eCollection 2021.
The accumulation of macrophages in degenerated discs is a common phenomenon. However, the roles and mechanisms of M2a macrophages in intervertebral disc degeneration (IDD) have not been illuminated. This study investigated the expression of the M2a macrophage marker (CD206) in human and rat intervertebral disc tissues by immunohistochemistry. To explore the roles of M2a macrophages in IDD, nucleus pulposus (NP) cells were co-cultured with M2a macrophages . To clarify whether the CHI3L1 protein mediates the effect of M2a macrophages on NP cells, siRNA was used to knock down CHI3L1 transcription. To elucidate the underlying mechanisms, NP cells were incubated with recombinant CHI3L1 proteins, then subjected to western blotting analysis of the IL-13Rα2 receptor and MAPK pathway. CD206-positive cells were detected in degenerated human and rat intervertebral disc tissues. Notably, M2a macrophages promoted the expression of catabolism genes (MMP-3 and MMP-9) and suppressed the expression of anabolism genes (aggrecan and collagen II) in NP cells. These effects were abrogated by CHI3L1 knockdown in M2a macrophages. Exposure to recombinant CHI3L1 promoted an extracellular matrix metabolic imbalance in NP cells the IL-13Rα2 receptor, along with activation of the ERK and JNK MAPK signaling pathways. This study elucidated the roles of M2a macrophages in IDD and identified potential mechanisms for these effects.
在退变的椎间盘内，巨噬细胞的聚集是一种常见现象。然而，M2a 巨噬细胞在椎间盘退变（IDD）中的作用和机制尚未阐明。本研究通过免疫组织化学方法检测了人及大鼠椎间盘组织中 M2a 巨噬细胞标志物（CD206）的表达。为了研究 M2a 巨噬细胞在 IDD 中的作用，将髓核细胞与 M2a 巨噬细胞共培养。为了阐明 CHI3L1 蛋白是否介导了 M2a 巨噬细胞对 NP 细胞的作用，用 siRNA 敲低 CHI3L1 转录。为了阐明潜在的机制，将 NP 细胞与重组 CHI3L1 蛋白孵育，然后进行白细胞介素 13 受体 α2 受体和 MAPK 通路的 Western blot 分析。在退变的人及大鼠椎间盘组织中检测到 CD206 阳性细胞。值得注意的是，M2a 巨噬细胞促进了 NP 细胞中分解代谢基因（MMP-3 和 MMP-9）的表达，抑制了合成代谢基因（聚集蛋白聚糖和胶原 II）的表达。在 M2a 巨噬细胞中敲低 CHI3L1 可消除这些作用。暴露于重组 CHI3L1 可促进 NP 细胞细胞外基质代谢失衡，这与白细胞介素 13 受体 α2 受体的激活以及 ERK 和 JNK MAPK 信号通路的激活有关。本研究阐明了 M2a 巨噬细胞在 IDD 中的作用，并确定了这些作用的潜在机制。
