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 (C 28 H 54 N 8 .8HCl), 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.
Aseptic meningitis sometimes occurs as consequence of central nervous system (CNS) involvement in patients with primary Sjögren’s syndrome (SS), even in pediatric-onset cases. However, little information is available regarding the pathological role of CSF anti-Ro/SSA and anti-La/SSB antibodies in the CNS involvement in patients with primary SS. We experienced an 18-year-old adolescent female with a 7-year history of suspicious of subclinical SS who subsequently developed aseptic meningitis as initial presentation of probable SS. Her CSF exhibited marked elevation of anti-Ro/SSA and anti-La/SSB antibodies. When compared to her CSF IgG/serum IgG ratio (0.0058), her CSF/serum ratios of anti-Ro/SSA and anti-La/SSB antibody titers were higher (0.448 and 0.068, respectively; these were 77.5 and 11.7 times higher than that of IgG, respectively), suggesting that regional production of these antibodies was attributable, at least partly, to the development of meningitis. After the initiation of prednisolone treatment, her clinical manifestations promptly subsided. Since the clinical and pathological roles of the Ro/SSA antibody system in several autoimmune conditions have been postulated, our clinical observation may add novel insight to this theory.
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