2. Academic Validation
  3. CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro

CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro

  • J Transl Med. 2023 Aug 25;21(1):573. doi: 10.1186/s12967-023-04449-0.
Xinzhe Feng # 1,  Shanbang Zhu # 1 2,  Junjie Qiao # 1,  Zhou Ji 1,  Bole Zhou 1,  Weidong Xu 3
Affiliations

Affiliations

  • 1 Department of Joint Bone Disease Surgery, Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China.
  • 2 Department of Orthopaedics, Affiliated Jinling Hospital, Medical School of Nanjing University, No 305 Zhongshandonglu Road, Nanjing, 210002, China.
  • 3 Department of Joint Bone Disease Surgery, Changhai Hospital, Naval Medical University, 168 Changhai Road, Shanghai, 200433, China. [email protected].
  • # Contributed equally.
PMID: 37626378 DOI: 10.1186/s12967-023-04449-0
Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords

Ankylosing spondylitis; CX3CL1; Intestinal inflammation; Macrophages.

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