Lysophosphatidic acid (LPA) is a lipid messenger mediated by G protein-coupled receptors (LPAR1-6). It is involved in the pathogenesis of certain chronic inflammatory and autoimmune diseases. In addition, it controls the self-renewal and differentiation of stem cells. Recent research has demonstrated the close relationship between periodontitis and various diseases in the human body. However, the precise role of LPA in the development of periodontitis has not been studied. We identified that LPAR1 was highly expressed in human periodontal ligament stem cells (PDLSCs). In periodontitis-mimicking conditions with Porphyromonas gingivalis -derived lipopolysaccharide (Pg-LPS) treatment, PDLSCs exhibited a considerable reduction in the cellular viability and osteogenic differentiation potential, in addition to an increase in the inflammatory responses including tumor necrosis factor-α and interleukin-1β expression and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation. Of the various LPAR antagonists, pre-treatment with AM095, an LPAR1 inhibitor, showed a positive effect on the restoration of cellular viability and osteogenic differentiation, accompanied by a decrease in NF-κB signaling, and action against Pg-LPS. These findings suggest that the modulation of LPAR1 activity will assist in checking the progression of periodontitis and in its treatment.

Introduction
Materials and Methods
    1. Cell culture and reagents
    2. Multilineage differentiation
    3. Immunocytochemistry
    4. Flow cytometry analysis
    5. RNA isolation and quantitative reverse transcriptionpolymerase chain reaction (RT-PCR)
    6. Proliferation assay
    7. Immunoblotting
    8. Induction of osteogenic differentiation
    9. Statistical analysis
Results
    1. Characterization of PDLSCs in MSC properties andLPAR expression
    2. Effect of LPAR antagonists on the viability ofPDLSCs
    3. Effect of LPAR antagonists on Pg-LPS-inducedviability decrease and inflammatory response
    4. Effect of LPAR1 antagonist on Pg-LPS-induceddecrease of osteogenic differentiation
Discussion
References

• Dong Hee Kim(Department of Oral Biochemistry, Pusan National University School of Dentistry/Dental and Life Science Institute, Pusan National University School of Dentistry/Department of Biological Sciences, College of Natural Sciences, University of Ulsan)
• Eun Jin Seo(Department of Oral Biochemistry, Pusan National University School of Dentistry/Dental and Life Science Institute, Pusan National University School of Dentistry)
• Gabor J. Tigyi(Department of Physiology, University of Tennessee Health Science Center)
• Byung Ju Lee(Department of Biological Sciences, College of Natural Sciences, University of Ulsan)
• Il Ho Jang(Department of Oral Biochemistry, Pusan National University School of Dentistry/Dental and Life Science Institute, Pusan National University School of Dentistry) Correspondence to