GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by P. gingivalis LPS and Concurrent Compression.
Albert StemmlerJudit SymmankJulia SteinmetzKatrin von BrandensteinChristoph-Ludwig HennigCollin JacobsPublished in: International journal of molecular sciences (2021)
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 P. gingivalis -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 GDF15 siRNA-treated HPdLF stimulated with P. gingivalis lipopolysaccharides alone and in combination with compressive force. GDF15 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.
Keyphrases
- inflammatory response
- oxidative stress
- diabetic rats
- induced apoptosis
- transforming growth factor
- high glucose
- single molecule
- endothelial cells
- lipopolysaccharide induced
- lps induced
- gene expression
- cell cycle arrest
- drug induced
- weight gain
- toll like receptor
- rheumatoid arthritis
- radiation therapy
- immune response
- anti inflammatory
- machine learning
- induced pluripotent stem cells
- big data
- electronic health record
- stress induced
- locally advanced
- artificial intelligence
- cancer therapy
- newly diagnosed
- postmenopausal women
- binding protein
- soft tissue