| 1759 Biomechanical Signals Regulate Proinflammatory and Osteogenic Gene Expression in PDL | ||
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S. MADHAVAN1, J. DESCHNER1, Z.-J. LIU2, G. KING3, and S. AGARWAL1, 1Ohio State University, Columbus, USA, 2University of Washington -, Seattle, USA, 3University of Washington, Seattle, USA Objectives: Bone and cementum deposition by cells of the periodontal ligament (PDL) is regulated by biomechanical forces. However, the molecular mechanisms underlying selective resorption and osteogenesis are poorly understood. We hypothesized that during alveolar bone remodeling tensile forces (TF) of low magnitudes (TFL) generate signals that are (1) anti-inflammatory and inhibit expression of pro-inflammatory mediators, (2) anabolic and upregulate osteogenic gene transcription. Methods: Human PDL cells harvested from the roots of third molars, were characterized, and grown on flexible bottom plates in the presence of IL-1, as an inflammatory signal. Cells subjected to TF of various magnitudes (3,6,9,12,15,18% tension) and unstretched cells were analyzed for the expression of proinflammatory and osteogenic genes and proteins by real-time PCR and Western blots. Additionally, maxillary first molars of Sprague-Dawley rats were tipped by orthodontic forces (40g). The expression of Cox-2 in the apical (lower force) and cervical (higher force) sections of these roots was examined immunohistochemically and quantified with Axioplan software. ANOVA was used for statistics. Results: In vitro, TFL (3-9%) inhibited IL-1 induced Cox-2 mRNA expression (92% + 8%; p<0.05) and synthesis in PDL cells. This suppression was mediated via inhibition of IkBß phosphorylation and degradation, preventing NFkB nuclear translocation and proinflammatory gene transcription. IL-1 inhibited osteopontin (89±6%), alkaline-phophatase (92±5.3%), and runx-2 (91±4.6%) induction, whereas TFL abrogated this inhibition by more than 78% in each case. In vivo, cervical sections of the first molar roots subjected to orthodontic forces revealed abundant expression of Cox-2 in PDL at both compressive and tensile sites. The apical sections exposed to TFL showed significant (p<0.01) suppression of Cox-2 at the tension sites. Untreated controls were negative for Cox-2 expression. Conclusions: These results provide persuasive evidence that, biomechanical signals produced by TFL regulate osteogenesis by inhibiting proinflammatory gene transcription and augmenting osteogenic gene expression. NIH DE15399, AT000646. | ||
| Seq #204 - Senior Category 2:00 PM-3:00 PM, Saturday, 11 March 2006 Dolphin Hotel Pacific Hall | ||
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