Lysophosphatidic acid (LPA) 18:1 transcriptional regulation of primary human gingival fibroblasts.

The pleiotropic, bioactive lipid lysophosphatidic acid [(LPA), 1-acyl-sn-glycerol-3-phosphate] exerts critical regulatory actions in physiology and pathophysiology in many systems. It is present in normal bodily fluids, and is elevated in pathology (1). In vivo, "LPA" exists as distinct molecular species, each having a single fatty acid of varying chain length and degree of unsaturation covalently attached to the glycerol backbone via an acyl, alkyl, or alkenyl link.

A Major Human Oral Lysophosphatidic Acid Species, LPA 18:1, Regulates Novel Genes in Human Gingival Fibroblasts.

Background: The small bioactive lipid lysophosphatidic acid (LPA) plays critical roles in both normal physiology and inflammation in many systems. However, its actions are just beginning to be defined in oral biology and pathophysiology.

Methods: Microarray analysis was used to test the hypothesis that human gingival fibroblasts (GFs) would show significant changes in wound-healing and inflammation-related gene transcripts in response to a major human salivary and gingival crevicular fluid LPA species, 18:1, and that they would express transcript for the major LPA-producing enzyme autotaxin.

Lysophosphatidic Acid signals through specific lysophosphatidic Acid receptor subtypes to control key regenerative responses of human gingival and periodontal ligament fibroblasts.

Background: We showed that the pluripotent platelet growth factor and mediator lysophosphatidic acid (LPA) controls key regenerative responses of human gingival fibroblasts (GFs) and periodontal ligament fibroblasts (PDLFs) and positively modulates their responses to platelet-derived growth factor (PDGF). This study determined which LPA receptor (LPAR) subtype(s) LPA signals through to stimulate mitogenic extracellular signal-regulated kinase (ERK) 1/2 signaling and chemotaxis and to elicit intracellular Ca(2+) increases in GFs and PDLFs because many healing responses are calcium-dependent.

Methods: Activation of mitogen-activated protein kinase was determined using Western blotting with an antibody to phosphorylated ERK1/2.

Lysophosphatidic acid modulates the healing responses of human periodontal ligament fibroblasts and enhances the actions of platelet-derived growth factor.

Background: Platelet-derived growth factor (PDGF) has been used to promote healing in many in vitro and in vivo models of periodontal regeneration. PDGF interacts extensively with lysophosphatidic acid (LPA). We recently showed that LPA modulates the responses of human gingival fibroblasts to PDGF.

Lysophosphatidic acid modulates the regenerative responses of human gingival fibroblasts and enhances the actions of platelet-derived growth factor.

Background: Platelet-derived growth factor (PDGF) has been used to promote healing in many in vitro and in vivo models of periodontal regeneration. PDGF is known to interact extensively with another platelet mediator, lysophosphatidic acid (LPA), to enhance regenerative responses in non-oral systems. PDGF and LPA are both liberated by platelets in the blood clot, which is known to be critical in stabilizing early periodontal wound healing.