Department of Joint Bone Disease Surgery, Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.
Department of Orthopaedics, Affiliated Jinling Hospital, Medical School of Nanjing University, No 305 Zhongshandonglu Road, Nanjing, 210002, China.
J Transl Med. 2023 Aug 25;21(1):573. doi: 10.1186/s12967-023-04449-0.
Ankylosing spondylitis (AS) is an autoimmune disease with a genetic correlation and is characterized by inflammation in the axial skeleton and sacroiliac joints. Many AS patients also have inflammatory bowel diseases (IBD), but the underlying causes of intestinal inflammation and osteoporosis in AS are not well understood. CX3CL1, a protein involved in inflammation, has been found to be up-regulated in AS patients and AS-model mice.
The authors investigated the effects of CX3CL1 on AS by studying its impact on macrophage polarization, inflammation factors, and osteoclast differentiation. Furthermore, the effects of inhibiting the NF-κB pathway and blocking CX3CL1 were assessed using BAY-117082 and anti-CX3CL1 mAb, respectively. AS model mice were used to evaluate the effects of anti-CX3CL1 mAb on limb thickness, spine rupture, and intestinal tissue damage.
The authors found that CX3CL1 increased the expression of M1-type macrophage markers and inflammation factors, and promoted osteoclast differentiation. This effect was mediated through the NF-κB signaling pathway. Inhibition of the NF-κB pathway prevented M1-type macrophage polarization, reduced inflammation levels, and inhibited osteoclast differentiation. Injection of anti-CX3CL1 mAb alleviated limb thickness, spine rupture, and intestinal tissue damage in AS model mice by inhibiting M1-type macrophage polarization and reducing intestinal tissue inflammation.
The study demonstrated that up-regulated CX3CL1 promotes M1-type macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway. Inhibition of this pathway and blocking CX3CL1 can alleviate inflammation and bone destruction in AS. These findings contribute to a better understanding of the pathogenesis of AS and provide a basis for clinical diagnosis and treatment.
强直性脊柱炎（AS）是一种具有遗传相关性的自身免疫性疾病，其特征是轴向骨骼和骶髂关节的炎症。许多 AS 患者也患有炎症性肠病（IBD），但 AS 中肠道炎症和骨质疏松的潜在原因尚不清楚。CX3CL1 是一种参与炎症的蛋白质，已被发现在 AS 患者和 AS 模型小鼠中上调。
作者通过研究其对巨噬细胞极化、炎症因子和破骨细胞分化的影响，研究了 CX3CL1 对 AS 的影响。此外，分别使用 BAY-117082 和抗 CX3CL1 mAb 评估了抑制 NF-κB 通路和阻断 CX3CL1 的效果。使用抗 CX3CL1 mAb 评估了 AS 模型小鼠对肢体厚度、脊柱破裂和肠道组织损伤的影响。
作者发现 CX3CL1 增加了 M1 型巨噬细胞标志物和炎症因子的表达，并促进了破骨细胞分化。这种作用是通过 NF-κB 信号通路介导的。抑制 NF-κB 通路可防止 M1 型巨噬细胞极化，降低炎症水平并抑制破骨细胞分化。注射抗 CX3CL1 mAb 通过抑制 M1 型巨噬细胞极化和减少肠道组织炎症来缓解 AS 模型小鼠的肢体厚度、脊柱破裂和肠道组织损伤。
该研究表明，上调的 CX3CL1 通过 NF-κB 信号通路促进 M1 型巨噬细胞极化和破骨细胞分化。抑制该通路和阻断 CX3CL1 可以缓解 AS 中的炎症和骨破坏。这些发现有助于更好地了解 AS 的发病机制，并为临床诊断和治疗提供依据。
