Analysis of lysophosphatidic acid signaling in periodontal ligament

Objectives: Periodontal ligament (PDL) is a connective tissue and acts as a cushion to a mechanical stress (MS) such as occlusal pressure between alveolar bone and the cementum of the dental root. Lysophosphatidic acid (LPA) is a new lipid mediator to regulate cell growth and development. We recently found the expressions of several LPA receptors and a synthetic enzyme of LPA in human periodontal ligament (PDL) cells and mouse tooth germ. There is a possibility that LPA might have an important role for a function of mature PDL and development of PDL in tooth germ. However, it is totally unclear. In this study, we attempted to reveal a role of LPA signals in PDL. Methods: PDL cells were isolated from human premolar teeth of patients extracted for orthodontic treatment. PDL cells were treated with 1µM LPA or MS with centrifuge for 2h. Total RNAs were isolated from PDL cells and the expression level of mRNA was compared between treated and untreated cells using DNA microarray. We also analyzed LPA receptor expression in mouse tooth germ by in situ hybridization. Results: In human PDL cells, LPA1 and LPA6 of LPA receptors were highly expressed; autotaxin (lyso-PLD) was also highly expressed, however, PA-PLA_1a and PS-PLA₁ were not expressed. MS stimulated autotaxin mRNA in human PDL cells. In mouse tooth germ, LPA1 was expressed in mesenchyme bordering to epithelium from ED12 to ED16. However, the expression was reversed from mesenchyme to epithelium at EP18 in which ameloblasts were existed. Conclusion: LPA signals have important roles for functions in mature PDL cells and development in tooth germ.