GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by <i>P. gingivalis</i> LPS and Concurrent Compression
Periodontitis is characterized by bacterially induced inflammatory destruction of periodontal tissue. This also affects fibroblasts of the human periodontal ligaments (HPdLF), which play a coordinating role in force-induced tissue and alveolar bone remodeling. Excessive inflammation in the oral tiss...
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| Format: | Article |
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MDPI AG
2021-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/24/13608 |
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| author | Albert Stemmler Judit Symmank Julia Steinmetz Katrin von Brandenstein Christoph-Ludwig Hennig Collin Jacobs |
| author_facet | Albert Stemmler Judit Symmank Julia Steinmetz Katrin von Brandenstein Christoph-Ludwig Hennig Collin Jacobs |
| author_sort | Albert Stemmler |
| collection | DOAJ |
| description | Periodontitis is characterized by bacterially induced inflammatory destruction of periodontal tissue. This also affects fibroblasts of the human periodontal ligaments (HPdLF), which play a coordinating role in force-induced tissue and alveolar bone remodeling. Excessive inflammation in the oral tissues has been observed with simultaneous stimulation by pathogens and mechanical forces. Recently, elevated levels of growth differentiation factor 15 (GDF15), an immuno-modulatory member of the transforming growth factor (TGFB) superfamily, were detected under periodontitis-like conditions and in force-stressed PdL cells. In view of the pleiotropic effects of GDF15 in various tissues, this study aims to investigate the role of GDF15 in <i>P. gingivalis</i>-related inflammation of HPdLF and its effect on the excessive inflammatory response to concurrent compressive stress. To this end, the expression and secretion of cytokines (IL6, IL8, COX2/PGE2, TNFα) and the activation of THP1 monocytic cells were analyzed in <i>GDF15</i> siRNA-treated HPdLF stimulated with <i>P. gingivalis</i> lipopolysaccharides alone and in combination with compressive force. <i>GDF15</i> knockdown significantly reduced cytokine levels and THP1 activation in LPS-stimulated HPdLF, which was less pronounced with additional compressive stress. Overall, our data suggest a pro-inflammatory role for GDF15 in periodontal disease and demonstrate that GDF15 partially modulates the force-induced excessive inflammatory response of PdLF under these conditions. |
| first_indexed | 2024-03-10T03:54:19Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T03:54:19Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1688a4d75f4446cf9c0094d823e2bfa12023-11-23T08:48:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0122241360810.3390/ijms222413608GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by <i>P. gingivalis</i> LPS and Concurrent CompressionAlbert Stemmler0Judit Symmank1Julia Steinmetz2Katrin von Brandenstein3Christoph-Ludwig Hennig4Collin Jacobs5Department of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyDepartment of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyDepartment of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyDepartment of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyDepartment of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyDepartment of Orthodontics, University Hospital Jena, Leutragraben 3, 07743 Jena, GermanyPeriodontitis is characterized by bacterially induced inflammatory destruction of periodontal tissue. This also affects fibroblasts of the human periodontal ligaments (HPdLF), which play a coordinating role in force-induced tissue and alveolar bone remodeling. Excessive inflammation in the oral tissues has been observed with simultaneous stimulation by pathogens and mechanical forces. Recently, elevated levels of growth differentiation factor 15 (GDF15), an immuno-modulatory member of the transforming growth factor (TGFB) superfamily, were detected under periodontitis-like conditions and in force-stressed PdL cells. In view of the pleiotropic effects of GDF15 in various tissues, this study aims to investigate the role of GDF15 in <i>P. gingivalis</i>-related inflammation of HPdLF and its effect on the excessive inflammatory response to concurrent compressive stress. To this end, the expression and secretion of cytokines (IL6, IL8, COX2/PGE2, TNFα) and the activation of THP1 monocytic cells were analyzed in <i>GDF15</i> siRNA-treated HPdLF stimulated with <i>P. gingivalis</i> lipopolysaccharides alone and in combination with compressive force. <i>GDF15</i> knockdown significantly reduced cytokine levels and THP1 activation in LPS-stimulated HPdLF, which was less pronounced with additional compressive stress. Overall, our data suggest a pro-inflammatory role for GDF15 in periodontal disease and demonstrate that GDF15 partially modulates the force-induced excessive inflammatory response of PdLF under these conditions.https://www.mdpi.com/1422-0067/22/24/13608periodontal diseaseGDF15orthodontic tooth movementinflammationPdL |
| spellingShingle | Albert Stemmler Judit Symmank Julia Steinmetz Katrin von Brandenstein Christoph-Ludwig Hennig Collin Jacobs GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by <i>P. gingivalis</i> LPS and Concurrent Compression International Journal of Molecular Sciences periodontal disease GDF15 orthodontic tooth movement inflammation PdL |
| title | GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by <i>P. gingivalis</i> LPS and Concurrent Compression |
| title_full | GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by <i>P. gingivalis</i> LPS and Concurrent Compression |
| title_fullStr | GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by <i>P. gingivalis</i> LPS and Concurrent Compression |
| title_full_unstemmed | GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by <i>P. gingivalis</i> LPS and Concurrent Compression |
| title_short | GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by <i>P. gingivalis</i> LPS and Concurrent Compression |
| title_sort | gdf15 supports the inflammatory response of pdl fibroblasts stimulated by i p gingivalis i lps and concurrent compression |
| topic | periodontal disease GDF15 orthodontic tooth movement inflammation PdL |
| url | https://www.mdpi.com/1422-0067/22/24/13608 |
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