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. The objectives of this study were as follows: 1) to evaluate the basic interactions of LPA with primary human periodontal ligament fibroblasts (PDLFs) alone and with PDGF-BB for promoting PDLF growth and migration; 2) to determine the effects in an in vitro oral wound-healing model; and 3) to identify the LPA receptors (LPARs) expressed by PDLF. Methods: PDLF regenerative responses were measured using 1 and 10 mu M LPA in the absence or presence of 1 or 10 ng/ml PDGF. Cell proliferation was determined by 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and by cell counting. Migration responses were measured using a microchemotaxis chamber. PDLFs were grown to confluence on glass slides, a 3-mm-wide wound was mechanically inflicted, and wound fill on days 4, 6, and 9 was reported. PDLF LPAR expression was determined using Western blotting. Results: PDLFs exhibited proliferative and chemotactic responses to LPA; these responses were enhanced when LPA and PDGF were present together. LPA plus PDGF elicited complete wound fill. PDLFs express the LPARs LPA(1), LPA(2), and LPA(3). Conclusions: To our knowledge, this study provides the first evidence that LPA stimulates human PDLF wound healing responses and interacts positively with PDGF to regulate these actions. These results suggest that LPA and its receptors play important modulatory roles in PDLF regenerative biology.