Lösch, L.; Stemmler, A.; Fischer, A.; Steinmetz, J.; Schuldt, L.; Hennig, C.-L.; Symmank, J.; Jacobs, C. GDF15 Promotes the Osteogenic Cell Fate of Periodontal Ligament Fibroblasts, thus Affecting Their Mechanobiological Response. Int. J. Mol. Sci.2023, 24, 10011.
Lösch, L.; Stemmler, A.; Fischer, A.; Steinmetz, J.; Schuldt, L.; Hennig, C.-L.; Symmank, J.; Jacobs, C. GDF15 Promotes the Osteogenic Cell Fate of Periodontal Ligament Fibroblasts, thus Affecting Their Mechanobiological Response. Int. J. Mol. Sci. 2023, 24, 10011.
Lösch, L.; Stemmler, A.; Fischer, A.; Steinmetz, J.; Schuldt, L.; Hennig, C.-L.; Symmank, J.; Jacobs, C. GDF15 Promotes the Osteogenic Cell Fate of Periodontal Ligament Fibroblasts, thus Affecting Their Mechanobiological Response. Int. J. Mol. Sci.2023, 24, 10011.
Lösch, L.; Stemmler, A.; Fischer, A.; Steinmetz, J.; Schuldt, L.; Hennig, C.-L.; Symmank, J.; Jacobs, C. GDF15 Promotes the Osteogenic Cell Fate of Periodontal Ligament Fibroblasts, thus Affecting Their Mechanobiological Response. Int. J. Mol. Sci. 2023, 24, 10011.
Abstract
Periodontal ligament fibroblasts (PdLFs) exert important functions in oral tissue and bone remodeling following mechanical forces, which are specifically applied during orthodontic tooth movement (OTM). Located between the teeth and the alveolar bone, mechanical stress activates the mechanomodulatory functions of PdLFs including the regulation of local inflammation and activation of further bone-remodeling cells. Previous studies suggested the growth differentiation factor 15 (GDF15) as important pro-inflammatory regulator during the PdLFs mechanoresponse. However, the precise mechanism remains to be clarified, as GDF15 may act both intracrine and by receptor binding, potentially also in an autocrine manner. The extent to which PdLFs are susceptible to extracellular GDF15 has not yet been investigated. Thus, our study aims to examine the influence of GDF15 exposure on cellular properties of PdLFs and their mechanoresponse, which seems particularly relevant regarding disease- and aging-associated elevated GDF15 serum levels. Therefore, in addition to investigating potential GDF15 receptors, we analyzed its impact on proliferation, survival, senescence, and differentiation of human PdLFs, demonstrating a pro-osteogenic effect upon long-term stimulation. Furthermore, we detected an altered force-related inflammation and impaired osteoclast differentiation. Overall, our data suggest a major impact of extracellular GDF15 on PdLFs differentiation and their mechanoresponse.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
