Abstract
PDL cells express GABAB1 and GABAB2 receptors, which are regulated by inflammation and thus might be implicated in periodontal immunology. It was the aim of this study to elucidate the functional role of GABAB receptors in immunomodulation regarding activation of proregenerative versus proinflammatory mechanisms. Human PDL cells were exposed to GABA and/or GABAB receptor antagonist CGP-52432 alone or in combination with IL-1β to mimic inflammation. The influence on marker expression for inflammatory tissue destruction was determined via qRT-PCR and Luminex assays. Proliferation and biomineralization were assessed by MTS assay and von Kossa staining. Statistical significance was set at p < 0.05. GABAB receptor blockade inhibited expression of IL-6, TNFα, MMP-3, and MMP-8 in an inflammatory milieu on transcriptional and on protein level, mediated by NF-κB. Besides, receptor blockade enhanced proliferation, especially under inflammatory conditions, and reduced mineralization in a non-inflammatory milieu. GABAB receptor activity on PDL cells is involved in the modulation of osteoimmunological processes in the periodontium and decides on the initiation versus prevention of host protective mechanisms. This implies anabolic potential for a therapeutic preservation or reestablishment of periodontal tissues under physiological and pathological conditions. In summary, GABAB receptor modulation in PDL cells might become an important target in immunoinflammatory settings.
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Acknowledgements
The authors would like to thank D. Nguyen and D. Stephens from the Forsyth Institute as much as K. Reifenrath and I. Bay-Müller from the Department of Orthodontics, University of Bonn for technical support. This research received Grant Support by the Deutsche Gesellschaft für Kieferorthopädie (DGKFO) and NIH/NIDCR Grant DE020906.
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Konermann, A., Van Dyke, T., Kantarci, A. et al. GABAB Receptors as Modulating Target for Inflammatory Responses of the Periodontal Ligament. Cell Mol Neurobiol 37, 1067–1076 (2017). https://doi.org/10.1007/s10571-016-0439-z
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DOI: https://doi.org/10.1007/s10571-016-0439-z