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

ABSTRACT: 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 es

SUBMITTER: Cui H 

PROVIDER: S-EPMC8986111 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature