Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248
CD248 (endosialin) belongs to a glycoprotein family that also includes thrombomodulin (CD141), CLEC14A, and CD93 (AA4) stem cell markers. We analyzed the regulated expression of CD248 in vitro using skin (HFFF) and synovial (FLS) mesenchymal stem cell lines, and in fluid and tissue samples of rheuma...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/11/9546 |
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| author | Melissa Payet Franck Ah-Pine Xavier Guillot Philippe Gasque |
| author_facet | Melissa Payet Franck Ah-Pine Xavier Guillot Philippe Gasque |
| author_sort | Melissa Payet |
| collection | DOAJ |
| description | CD248 (endosialin) belongs to a glycoprotein family that also includes thrombomodulin (CD141), CLEC14A, and CD93 (AA4) stem cell markers. We analyzed the regulated expression of CD248 in vitro using skin (HFFF) and synovial (FLS) mesenchymal stem cell lines, and in fluid and tissue samples of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells were incubated with either rhVEGF<sub>165</sub>, bFGF, TGF-β1, IL1-β, TNF-α, TGFβ1, IFN-γ, or PMA (Phorbol ester). There was no statistically significant change in membrane expression. A soluble (s) form of cleaved CD248 (sCD248) was detected after cell treatment with IL1-β and PMA. Matrix metalloprotease (MMP) MMP-1 and MMP-3 mRNAs were significantly up-regulated by IL1-β and PMA. A broad MMP inhibitor blocked the release of soluble CD248. In RA synovial tissue, we identified CD90<sup>+</sup> perivascular MSCs double-stained for CD248 and VEGF. High sCD248 levels were detected in synovial fluid from RA. In culture, subpopulations of CD90<sup>+</sup> CD14<sup>−</sup> RA MSCs were either identified as CD248<sup>+</sup> or CD141<sup>+</sup> cells but CD93<sup>−</sup>. CD248 is abundantly expressed by inflammatory MSCs and shed in an MMP-dependent manner in response to cytokines and pro-angiogenic growth factors. Both membrane-bound and soluble CD248 (acting as a decoy receptor) may contribute to RA pathogenesis. |
| first_indexed | 2024-03-11T03:05:24Z |
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| id | doaj.art-26ec3010a5c6461387d067e1b4b72fd5 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:05:24Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-26ec3010a5c6461387d067e1b4b72fd52023-11-18T08:00:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012411954610.3390/ijms24119546Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248Melissa Payet0Franck Ah-Pine1Xavier Guillot2Philippe Gasque3Unité de Recherche en Pharmaco-Immunologie (EPI), Université et CHU de La Réunion, 97400 Saint-Denis, FranceUnité de Recherche en Pharmaco-Immunologie (EPI), Université et CHU de La Réunion, 97400 Saint-Denis, FranceUnité de Recherche en Pharmaco-Immunologie (EPI), Université et CHU de La Réunion, 97400 Saint-Denis, FranceUnité de Recherche en Pharmaco-Immunologie (EPI), Université et CHU de La Réunion, 97400 Saint-Denis, FranceCD248 (endosialin) belongs to a glycoprotein family that also includes thrombomodulin (CD141), CLEC14A, and CD93 (AA4) stem cell markers. We analyzed the regulated expression of CD248 in vitro using skin (HFFF) and synovial (FLS) mesenchymal stem cell lines, and in fluid and tissue samples of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells were incubated with either rhVEGF<sub>165</sub>, bFGF, TGF-β1, IL1-β, TNF-α, TGFβ1, IFN-γ, or PMA (Phorbol ester). There was no statistically significant change in membrane expression. A soluble (s) form of cleaved CD248 (sCD248) was detected after cell treatment with IL1-β and PMA. Matrix metalloprotease (MMP) MMP-1 and MMP-3 mRNAs were significantly up-regulated by IL1-β and PMA. A broad MMP inhibitor blocked the release of soluble CD248. In RA synovial tissue, we identified CD90<sup>+</sup> perivascular MSCs double-stained for CD248 and VEGF. High sCD248 levels were detected in synovial fluid from RA. In culture, subpopulations of CD90<sup>+</sup> CD14<sup>−</sup> RA MSCs were either identified as CD248<sup>+</sup> or CD141<sup>+</sup> cells but CD93<sup>−</sup>. CD248 is abundantly expressed by inflammatory MSCs and shed in an MMP-dependent manner in response to cytokines and pro-angiogenic growth factors. Both membrane-bound and soluble CD248 (acting as a decoy receptor) may contribute to RA pathogenesis.https://www.mdpi.com/1422-0067/24/11/9546mesenchymal stem cellsCD248inflammationrheumatoid arthritis |
| spellingShingle | Melissa Payet Franck Ah-Pine Xavier Guillot Philippe Gasque Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248 International Journal of Molecular Sciences mesenchymal stem cells CD248 inflammation rheumatoid arthritis |
| title | Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248 |
| title_full | Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248 |
| title_fullStr | Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248 |
| title_full_unstemmed | Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248 |
| title_short | Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248 |
| title_sort | inflammatory mesenchymal stem cells express abundant membrane bound and soluble forms of c type lectin like cd248 |
| topic | mesenchymal stem cells CD248 inflammation rheumatoid arthritis |
| url | https://www.mdpi.com/1422-0067/24/11/9546 |
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