Artikel
Tetraspanin 30 and 24 influence the adhesion and migration of rheumatoid synovial fibroblasts
Suche in Medline nach
Autoren
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Nick Lennart Bajors
- Justus Liebig University Giessen, Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Bad Nauheim
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Mona Arnold
- Justus Liebig University Giessen, Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Bad Nauheim
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Klaus Frommer
- Justus Liebig University Giessen, Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Bad Nauheim
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Markus Rickert
- University Hospital Giessen and Marburg, Department of Orthopaedics and Orthopaedic Surgery, Giessen
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Stefan Rehart
- Agaplesion Markus Hospital, Department of Orthopaedics and Trauma Surgery, Frankfurt
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Ulf Müller-Ladner
- Justus Liebig University Giessen, Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Bad Nauheim
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Elena Neumann
- Justus Liebig University Giessen, Department of Rheumatology and Clinical Immunology, Campus Kerckhoff, Bad Nauheim
| Veröffentlicht: | 18. September 2024 |
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Gliederung
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Introduction: In rheumatoid arthritis (RA), the migration of RA synovial fibroblasts (RASF) from affected joints is a hypothesis to explain spreading within a joint or between joints in RA. Tetraspanins are cell membrane proteins that influence adhesion molecules such as integrins and thus influence the cytoskeleton and the motility of the cell. Some tetraspanins are involved in the metastasis of various tumors and presumably also in the migration of RASF, which has already been shown for CD82. CD63 (tetraspanin 30) has a predominantly migration-inhibiting effect and CD151 (tetraspanin 24) has a migration-promoting effect. They are also expressed to different degrees in the lining layer and sublining of RA synovium.
Objectives: To test whether CD63 and CD151 influence the adhesion and migration behavior of RASF.
Methods: A vector (overexpression), siRNA (knockout) or PBS (mock control) was transfected into RASF by nucleofection. The altered expression of CD63 and CD151 RNA was quantified over time by real-time PCR. The protein levels of the tetraspanins were quantified using immunocytochemistry and Western blot. Short-term adhesion tests and scratch assays were performed with the transfected RASF.
Results: Overexpression of CD63 and CD151 reduced RASF adhesion compared to the mock control (100%). The effects of CD63 (55.8%, n=3) and CD151 (54.8%, n=5) were on a similar level. The knockout of CD63 (93.0%, n=3) and CD151 (96.7%, n=5) showed no effect on adhesion. The overexpression reduced the migration of both, CD151 (33.7%, n=3) and CD63 (52.5%, n=2), compared to control (100%). In contrast, the knockout showed no effect on cell motility for CD63 (99.7%, n=2) and CD151 (92.9%, n=3).
Conclusion: In vitro, the overexpression of CD63 and CD151 each leads to reduced adhesion and migration. This is consistent with the reduced migration potential after overexpression of the tetraspanin CD82. Following this, it could be postulated that the tetraspanins inhibit RASF cell migration via tetraspanin-enriched microdomains, particularly in the area of cartilage invasion keeping the cells at the sites of inflammation and invasion.
