Mechanical Stress-induced Gene Expression Essential for HPLF Growth

Objectives: Differential expression of genes in human periodontal ligament fibroblasts (HPLF) under physiological stress such as occlusal force is thought to be associated not only with the remodeling of ligament itself but also with the repair or regeneration of periodontal tissues. We aimed to reveal the changes of gene expression induced by mechanical stress in cultured HPLF. Methods: The cells were isolated from the periodontal ligaments of three donors, and subjected to 18% elongation at 6 cycles per minute for 0.5, 1, 2, and 16 hours using the Flexercell Strain Unit. Total RNA was recovered from the mechanical stress-applied and from stress-free cells as a control, and analyzed for gene expression using the oligonucleotide arrays spotted about 8,500 known human genes. The analysis and its data mining were performed as described previously (J Dent Res, 81: 679-682, 2003), and an ANOVA and k-means clustering analyses were performed. Results: The 122 genes changed their expression significantly. They were assigned into 8 clusters of unique gene regulation patterns including the up-regulation between 0.5 and 2 hours and the down-regulation at 16 hours of the deleted in liver cancer 1, dual specificity phosphatase 6, and tribbles homolog 1; and the up-regulation at 1 and 2 hours of the cytochrome c and TGF-b inducible early growth response. These genes belonged to Cell Growth and Maintenance category based on the GeneSpring Database. In the other clusters, many genes, whose expressions were up-regulated in either period, belonged to the category. Conclusion: These results indicate that the differentially expressed genes by mechanical stress may be essential for HPLF growth because these genes are related to the cell growth and maintenance. This study was supported by a Grant-in-Aid for Exploratory Research (No. 16659579) and a Grant-in-Aid for Scientific Research A (No. 16209063) from the JSPS.