Inhibitory Effects of Tumor Necrosis Factor-Alpha on Migration of Human Periodontal Ligament Cells

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Tumor necrosis factor-alpha (TNF-α) is associated with chronic gingival inflammation and is suspected to influence periodontal destruction. However, the exact roles of TNF-α in wound healing and periodontal tissue regeneration are largely unknown. In the present study, we examined the effects of TNF-α on migration and proliferation of human periodontal ligament (PDL) cells.


PDL cells were cultured in the presence of TNF-α to determine its effects on cellular migration and proliferation. The protein expression profiles of α5 and β1 integrin subunits and their related molecules, paxillin and focal adhesion kinases (FAK), were investigated. Gene expression of fibronectin also was assayed. Further, the activation of Rho-family small guanosine triphosphate (GTP)-binding protein (RhoA) was evaluated using a GTP-loading pull-down assay, and focal adhesion formation by PDL cells after transfection with the expression vector of paxillin-fused green fluorescent protein (GFP) also was observed with confocal microscopy.


Cellular migration was impaired by TNF-α and recovered following the addition of anti-TNF-α antibodies. In contrast, PDL cell proliferation was not affected by TNF-a. TNF-α upregulated the expression of the α5 and β1 integrin subunits, whereas fibronectin was not overexpressed. Phosphorylation of paxillin and FAK by PDL cells was induced, and RhoA activation also was induced. Confocal microscopic analysis revealed that TNF-α induced focal adhesion and stress fiber formation in all parts of the cells.


Our results suggested that TNF-α impairs cellular migration by enhancing cellular adhesive ability following significant focal adhesion and stress fiber formation. J Periodontol 2006;77:883-890.

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