Int J Oral Biol.  2020 Jun;45(2):42-50. 10.11620/IJOB.2020.45.2.42.

The role of lysophosphatidic acid receptor 1 in inflammatory response induced by lipopolysaccharide from Porphyromonas gingivalis in human periodontal ligament stem cells

Affiliations
  • 1Department of Oral Biochemistry, Pusan National University School of Dentistry, Yangsan 50612, Republic of Korea
  • 2Dental and Life Science Institute, Pusan National University School of Dentistry, Yangsan 50612, Republic of Korea
  • 3Department of Biological Sciences, College of Natural Sciences, University of Ulsan, Ulsan 44610, Republic of Korea
  • 4Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA

Abstract

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.

Keyword

Periodontal ligament stem cell; Periodontitis; Lysophosphatidic acid receptor
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