CXCL12/CXCR4-Rac1-mediated migration of osteogenic precursor cells contributes to pathological new bone formation in ankylosing spondylitis.
CXCL12/CXCR4-Rac1-mediated migration of osteogenic precursor cells contributes to pathological new bone formation in ankylosing spondylitis.
复制标题
DOI：
10.1126/sciadv.abl8054
复制
发表时间：
2022-04-08
期刊：
影响因子：
13.6
通讯作者：
Liu H
中科院分区：
文献类型：
--
作者：
Cui H;Li Z;Chen S;Li X;Chen D;Wang J;Li Z;Hao W;Zhong F;Zhang K;Zheng Z;Zhan Z;Liu H
强直性脊柱炎(AS)是一种慢性炎症性疾病，其特征是炎症性背痛和由于病理性新骨形成而导致的脊柱强直。在这里，我们确定CXCL12是通过募集成骨前体细胞(OPC)而在病理性新骨形成中起关键作用的。CXCL12在可能形成病理性新骨的区域高表达。OPC被招募到CXCL12上调的地区。在AS动物模型中，用AMD3100抑制CXCL12/CXCR4轴或条件性敲除CXCR4可减少OPC的迁移和随后的病理性新骨形成。相比之下，CXCL12过表达的基因工程动物模型出现了关节强直的表型。此外，还发现rac1是OPC迁移和病理性新骨形成所必需的。这些发现削弱了CXCL12在AS中的新作用，并表明了一种潜在的靶向CXCL12/CXCR4-rac1轴的策略，以防止中轴性骨骼强直的进展。CXCL12/CXCR4轴介导的OPC迁移参与了强直性脊柱炎的病理性新骨形成。
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 axis–mediated migration of OPCs contributes to pathological new bone formation in ankylosing spondylitis.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
6.2
作者：
Baraliakos, Xenofon;Braun, Juergen;Fierlinger, Anke
通讯作者：
Fierlinger, Anke
影响因子：
--
作者：
Berlo, Suzanne E.;Guichelaar, Teun;Glant, Tibor T.
通讯作者：
Glant, Tibor T.
影响因子：
27.4
作者：
Jacques, Peggy;Lambrecht, Stijn;Elewaut, Dirk
通讯作者：
Elewaut, Dirk
影响因子：
11.5
作者：
Ghobrial, Irene M.;Liu, Chia-Jen;Becker, Pamela S.
通讯作者：
Becker, Pamela S.