@article {Chinjpet.118.254367, author = {Shunfu Chin and Ken-Ichi Furukawa and Keigo Kurotaki and Shunpei Nagasaki and Kanichiro Wada and Gentaro Kumagai and Shigeru Motomura and Yasuyuki Ishibashi}, title = {Facilitation of chemotaxis activity of mesenchymal stem cells via stromal cell-derived factor-1 and its receptor may promote ectopic ossification of human spinal ligaments}, elocation-id = {jpet.118.254367}, year = {2019}, doi = {10.1124/jpet.118.254367}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Mesenchymal stem cells (MSCs) have been utilized to elucidate the pathogenesis of numerous diseases. Our recent study showed that MSCs may conduce to the ossification of spinal ligaments. Stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) regulate MSC migration. Moreover, their expression is elevated in sites of damage and remodeling in pathological states. We explored the possible role of the SDF-1/CXCR4 axis in chemotactic behavior of MSCs in ossification of spinal ligaments. Specimens of thoracic vertebra ossified ligamentum flavum (OLF) and non-OLF plaques were received from patients whom we had performed spine surgery. Paraffin-embedded tissue sections were prepared for immunohistochemical staining. Cultured MSCs from the ligamentum flavum were prepared for in vitro analyses. We observed SDF-1 and CXCR4 localization immunohistochemically in the perivascular area and collagenous matrix of ligaments and in chondrocytes near the ossification front of OLF. And then, immunohistochemical staining showed a close relationship between MSCs and the SDF-1/CXCR4. In the in vitro analyses, expression of the SDF-1/CXCR4 and the migratory capacity of MSCs in OLF were remarkably higher compared with non-OLF. Furthermore, the migration of MSCs was up-regulated by SDF-1 and down-regulated by treatment with AMD3100, a specific antagonist for CXCR4. All in vitro test data showed a significant difference in MSCs from OLF compared with non-OLF. Our results reveal that the SDF-1/CXCR4 axis may contribute to an MSC-mediated increase in the ossification process, indicating that SDF-1/CXCR4 axis may become a potential target for a novel therapeutic strategy for ossification of spinal ligaments.}, issn = {0022-3565}, URL = {https://jpet.aspetjournals.org/content/early/2019/01/28/jpet.118.254367}, eprint = {https://jpet.aspetjournals.org/content/early/2019/01/28/jpet.118.254367.full.pdf}, journal = {Journal of Pharmacology and Experimental Therapeutics} }