CXCL12/CXCR4-Rac1-mediated migration of osteogenic precursor cells contributes to pathological new bone formation in ankylosing spondylitis.
Haowen CuiZihao LiSiwen ChenXiang LiDongying ChenJianru WangZemin LiWenjun HaoFangling ZhongKuibo ZhangZhaomin ZhengZhongping ZhanHui LiuPublished in: Science advances (2022)
Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by inflammatory back pain and spinal ankylosis due to pathological new bone formation. Here, we identified CXCL12 as a critical contributor to pathological new bone formation through recruitment of osteogenic precursor cells (OPCs). CXCL12 was found highly expressed in the regions that would potentially develop pathological new bone. OPCs were recruited to the regions where CXCL12 was up-regulated. Inhibition of CXCL12/CXCR4 axis with AMD3100 or conditional knockout of CXCR4 attenuated OPCs migration and subsequent pathological new bone formation in animal models of AS. By contrast, a genetically engineered animal model with CXCL12 overexpression developed a joint ankylosis phenotype. Furthermore, Rac1 was found essential for OPCs migration and pathological new bone formation. These findings ravel the novel role of CXCL12 in AS and indicate a potential strategy for targeting the CXCL12/CXCR4-Rac1 axis to prevent progression of axial skeleton ankylosis.
Keyphrases
- systemic lupus erythematosus
- disease activity
- ankylosing spondylitis
- cell migration
- induced apoptosis
- rheumatoid arthritis
- oxidative stress
- bone marrow
- magnetic resonance
- cell cycle arrest
- cell proliferation
- bone mineral density
- drug delivery
- cell death
- spinal cord injury
- risk assessment
- cancer therapy
- endoplasmic reticulum stress
- human health
- climate change
- drug induced