GDF15 Contributes to the Regulation of the Mechanosensitive Responses of PdL Fibroblasts through the Modulation of IL-37
During orthodontic tooth movement (OTM), areas of compressive and tensile forces are generated in the periodontal ligament (PdL), a mechanoreactive connective tissue between the teeth and alveolar bone. Mechanically stimulated PdL fibroblasts (PdLFs), the main cell type of PdL, express significantly...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Dentistry Journal |
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| Online Access: | https://www.mdpi.com/2304-6767/12/2/39 |
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| author | Julia Steinmetz Albert Stemmler Christoph-Ludwig Hennig Judit Symmank Collin Jacobs |
| author_facet | Julia Steinmetz Albert Stemmler Christoph-Ludwig Hennig Judit Symmank Collin Jacobs |
| author_sort | Julia Steinmetz |
| collection | DOAJ |
| description | During orthodontic tooth movement (OTM), areas of compressive and tensile forces are generated in the periodontal ligament (PdL), a mechanoreactive connective tissue between the teeth and alveolar bone. Mechanically stimulated PdL fibroblasts (PdLFs), the main cell type of PdL, express significantly increased levels of growth differentiation factor 15 (GDF15). In compressed PdL areas, GDF15 plays a fundamental role in modulating relevant OTM processes, including inflammation and osteoclast activation. However, the specific function of this factor in tensile areas has not yet been investigated. Thus, the aim of this study was to investigate the role of GDF15 in the mechanoresponse of human PdLFs (hPdLFs) that were exposed to biaxial tensile forces in vitro. Using siRNA-mediated knockdown experiments, we demonstrated that GDF15 had no impact on the anti-inflammatory force response of elongated hPdLFs. Although the anti-inflammatory markers <i>IL1RN</i> and <i>IL10</i>, as well as the activation of immune cells remained unaffected, we demonstrated an inhibitory role of GDF15 for the IL-37 expression. By analyzing osteogenic markers, including <i>ALPL</i> and <i>RUNX2</i>, along with an assessment of alkaline phosphatase activation, we further showed that the regulation of IL-37 by GDF15 modulates the osteogenic differentiation potential of hPdLFs. Despite bone resorption in tensile areas being rather limited, GDF15 was also found to positively modulate osteoclast activation in those areas, potentially by adjusting the IL-37 levels. In light of our new findings, we hypothesize that GDF15 modulates force-induced processes in tissue and bone remodeling through its various intra- and extracellular signaling pathways as well as interaction partners. Potentially acting as a master regulator, the modulation of GDF15 levels may hold relevance for clinical implications. |
| first_indexed | 2024-03-07T22:35:34Z |
| format | Article |
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| issn | 2304-6767 |
| language | English |
| last_indexed | 2024-03-07T22:35:34Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
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| series | Dentistry Journal |
| spelling | doaj.art-7db5dc9646e0430f9bf4a646fcec70de2024-02-23T15:13:35ZengMDPI AGDentistry Journal2304-67672024-02-011223910.3390/dj12020039GDF15 Contributes to the Regulation of the Mechanosensitive Responses of PdL Fibroblasts through the Modulation of IL-37Julia Steinmetz0Albert Stemmler1Christoph-Ludwig Hennig2Judit Symmank3Collin Jacobs4Department of Orthodontics, University Hospital Jena, 07743 Jena, GermanyDepartment of Orthodontics, University Hospital Jena, 07743 Jena, GermanyDepartment of Orthodontics, University Hospital Jena, 07743 Jena, GermanyDepartment of Orthodontics, University Hospital Jena, 07743 Jena, GermanyDepartment of Orthodontics, University Hospital Jena, 07743 Jena, GermanyDuring orthodontic tooth movement (OTM), areas of compressive and tensile forces are generated in the periodontal ligament (PdL), a mechanoreactive connective tissue between the teeth and alveolar bone. Mechanically stimulated PdL fibroblasts (PdLFs), the main cell type of PdL, express significantly increased levels of growth differentiation factor 15 (GDF15). In compressed PdL areas, GDF15 plays a fundamental role in modulating relevant OTM processes, including inflammation and osteoclast activation. However, the specific function of this factor in tensile areas has not yet been investigated. Thus, the aim of this study was to investigate the role of GDF15 in the mechanoresponse of human PdLFs (hPdLFs) that were exposed to biaxial tensile forces in vitro. Using siRNA-mediated knockdown experiments, we demonstrated that GDF15 had no impact on the anti-inflammatory force response of elongated hPdLFs. Although the anti-inflammatory markers <i>IL1RN</i> and <i>IL10</i>, as well as the activation of immune cells remained unaffected, we demonstrated an inhibitory role of GDF15 for the IL-37 expression. By analyzing osteogenic markers, including <i>ALPL</i> and <i>RUNX2</i>, along with an assessment of alkaline phosphatase activation, we further showed that the regulation of IL-37 by GDF15 modulates the osteogenic differentiation potential of hPdLFs. Despite bone resorption in tensile areas being rather limited, GDF15 was also found to positively modulate osteoclast activation in those areas, potentially by adjusting the IL-37 levels. In light of our new findings, we hypothesize that GDF15 modulates force-induced processes in tissue and bone remodeling through its various intra- and extracellular signaling pathways as well as interaction partners. Potentially acting as a master regulator, the modulation of GDF15 levels may hold relevance for clinical implications.https://www.mdpi.com/2304-6767/12/2/39GDF15IL-37periodontal ligament fibroblastsorthodontic tooth movementtension |
| spellingShingle | Julia Steinmetz Albert Stemmler Christoph-Ludwig Hennig Judit Symmank Collin Jacobs GDF15 Contributes to the Regulation of the Mechanosensitive Responses of PdL Fibroblasts through the Modulation of IL-37 Dentistry Journal GDF15 IL-37 periodontal ligament fibroblasts orthodontic tooth movement tension |
| title | GDF15 Contributes to the Regulation of the Mechanosensitive Responses of PdL Fibroblasts through the Modulation of IL-37 |
| title_full | GDF15 Contributes to the Regulation of the Mechanosensitive Responses of PdL Fibroblasts through the Modulation of IL-37 |
| title_fullStr | GDF15 Contributes to the Regulation of the Mechanosensitive Responses of PdL Fibroblasts through the Modulation of IL-37 |
| title_full_unstemmed | GDF15 Contributes to the Regulation of the Mechanosensitive Responses of PdL Fibroblasts through the Modulation of IL-37 |
| title_short | GDF15 Contributes to the Regulation of the Mechanosensitive Responses of PdL Fibroblasts through the Modulation of IL-37 |
| title_sort | gdf15 contributes to the regulation of the mechanosensitive responses of pdl fibroblasts through the modulation of il 37 |
| topic | GDF15 IL-37 periodontal ligament fibroblasts orthodontic tooth movement tension |
| url | https://www.mdpi.com/2304-6767/12/2/39 |
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