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
| Autor: | Shigeru Motomura, Yasuyuki Ishibashi, Keigo Kurotaki, Shunpei Nagasaki, Ken-Ichi Furukawa, Gentaro Kumagai, Kanichiro Wada, Shunfu Chin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0301 basic medicine Receptors CXCR4 Pathology medicine.medical_specialty Stromal cell Matrix (biology) CXCR4 Young Adult 03 medical and health sciences 0302 clinical medicine medicine Humans Stromal cell-derived factor 1 CXC chemokine receptors Aged Aged 80 and over Pharmacology Ligaments biology Ossification Chemotaxis Ossification Heterotopic Mesenchymal stem cell Mesenchymal Stem Cells Middle Aged Chemokine CXCL12 Spine Protein Transport 030104 developmental biology biology.protein Molecular Medicine Immunohistochemistry Female medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Journal of Pharmacology and Experimental Therapeutics. 369:1-8 |
| ISSN: | 1521-0103 0022-3565 |
| Popis: | Mesenchymal stem cells (MSCs) have been used 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 pathologic states. We explored the possible role of the SDF-1/CXCR4 axis in the chemotactic behavior of MSCs in the ossification of spinal ligaments. Specimens of thoracic vertebra ossified ligamentum flavum (OLF) and non-OLF plaques were received from patients in 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 axis. 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 MSCs. Furthermore, the migration of MSCs was upregulated by SDF-1 and downregulated by treatment with AMD3100 (C28H54N88HCl), a specific antagonist for CXCR4. All in vitro test data showed a significant difference in MSCs from OLF compared with non-OLF MSCs. Our results reveal that the SDF-1/CXCR4 axis may contribute to an MSC-mediated increase in the ossification process, indicating that the SDF-1/CXCR4 axis may become a potential target for a novel therapeutic strategy for ossification of spinal ligaments. |
| Databáze: | OpenAIRE |
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