Crosstalk Between Lysophosphatidic Acid and Mechanical Stress in Periodontal Ligament

Objective: Lysophosphatidic acid (LPA) is a new lipid mediator to affect several biological functions such as cell growth and development. LPA is existed in serum and regulates maintenance of cells and tissues. We recently found the expressions of LPA receptors in human periodontal ligament (PDL) cells. However, the function of LPA signaling in PDL cells is totally unclear. We also found that mechanical stress (MS) had an important role to maintain PDL cells via an induction of several genes including an enzyme for LPA synthesis. In this study, we attempted to reveal a role of a signaling crosstalk between LPA and MS in PDL cells. Method: PDL cells were isolated from human premolar teeth of patients extracted for orthodontic treatment. PDL cells were treated with MS using centrifuge or LPA (1µM). An induction of mRNA by MS and LPA was determined using RT-PCR analyses and DNA microarray. Cell lysates were isolated to analyze an intercellular signaling pathway including MAP kinase phosphorylation. LPA produced from PDL cells was analyzed by Thin-Layer Chromatography using ¹⁴C-labeled palmitic acid and lysophosphatidylcholine. Result: An enzyme for LPA synthesis, lyso-Phospholipase D (lyso-PLD) was induced by MS after 6h. ERK phosphorylation was determined by MS or LPA treatment at 10 min. LPA was synthesized by PDL cell with MS. IL-11 and NR4A3 (the member 3 of group A in nuclear receptor superfamily 4) was induced by both MS and LPA treatment. Conclusion: LPA treatment and MS stimulated several common signaling pathways such as ERK phosphorylation and induction of genes such as IL-11 and NR4A3 in PDL cells. MS also induced lyso-PLD in PDL cells. Thus, signaling crosstalk between LPA and MS might have an important role for maintenance of PDL cells.