Gene

Cell biology

Biology

Chemokine

Surgery

RAC1

Ankylosis

Signal transduction

CXCR4

Ankylosing spondylitis

Immunology

Genetics

Inflammation

Pathological

Conditional gene knockout

Medicine

Phenotype

Pathology

Science Advances

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.

CXCL12/CXCR4-Rac1–mediated migration of osteogenic precursor cells contributes to pathological new bone formation in ankylosing spondylitis