Lysophosphatidic Acid Modulates the Healing Responses of Human Periodontal Ligament Fibroblasts and Enhances the Actions of Platelet‐Derived Growth Factor

Cerutis, D. Roselyn; Dreyer, A; Vierra, Matthew J.; King, Joshua P.; Wagner, David J.; Fimple, Jacob L.; Cordini, Franco; McVaney, Timothy P.; Parrish, Lawrence C.; Wilwerding, Terrence M.; Mattson, John S.

doi:10.1902/jop.2007.060442

Cited by 13 publications

(16 citation statements)

References 47 publications

(69 reference statements)

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“…LPA markedly enhance the growth of cells of esophagus, pharynx, and tongue origin in vitro (Sugiura et al, 2002). Lysophosphatidic acids also stimulate the healing responses of human periodontal ligament fibroblasts and interact positively with PDGF (Cerutis et al, 2007).…”

Section: Lpa In Wound Healingmentioning

confidence: 99%

Lysophosphatidic acids, cyclic phosphatidic acids and autotaxin as promising targets in therapies of cancer and other diseases.

Gendaszewska‐Darmach¹

2008

Acta Biochim Pol

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Lysophospholipids have long been recognized as membrane phospholipid metabolites, but only recently lysophosphatidic acids (LPA) have been demonstrated to act on specific G protein-coupled receptors. The widespread expression of LPA receptors and coupling to several classes of G proteins allow LPA-dependent regulation of numerous processes, such as vascular development, neurogenesis, wound healing, immunity, and cancerogenesis. Lysophosphatidic acids have been found to induce many of the hallmarks of cancer including cellular processes such as proliferation, survival, migration, invasion, and neovascularization. Furthermore, autotaxin (ATX), the main enzyme converting lysophosphatidylcholine into LPA was identified as a tumor cell autocrine motility factor. On the other hand, cyclic phosphatidic acids (naturally occurring analogs of LPA generated by ATX) have anti-proliferative activity and inhibit tumor cell invasion and metastasis. Research achievements of the past decade suggest implementation of preclinical and clinical evaluation of LPA and its analogs, LPA receptors, as well as autotaxin as potential therapeutic targets.

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Section: Lpa In Wound Healingmentioning

confidence: 99%

Lysophosphatidic acids, cyclic phosphatidic acids and autotaxin as promising targets in therapies of cancer and other diseases.

Gendaszewska‐Darmach¹

2008

Acta Biochim Pol

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“…The latest studies in this area have shown that PDGF works in synergy with other signaling molecules, particularly in the regulation of proliferation. For example, PDGF has been shown to enhance the proliferative effect of lysophosphatidic acid on periodontal ligament fibroblasts and stimulate complete wound closure (35). Also, thrombospondin has been reported to be an important mediator of PDGF-DD-stimulated migration and proliferation of retinal pericytes (36).…”

Section: Modulation Of Pdgf and Pdgfr By Integrins And Other Cell Surmentioning

confidence: 99%

Platelet-derived growth factor signaling in mesenchymal cells

Donovan¹

2013

Front Biosci

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Platelet-derived growth factors (PDGFs) and their receptors are major mitogens for many cell types of mensenchymal origin, including fibroblasts and vascular smooth muscle cells (VSMCs). Their role in enhancing migratory and proliferative responses and extracellular matrix synthesis in these cells, make them key regulators of critical biological functions and in tissue diseases including tissue remodeling, scarring and fibrosis. The activities of the PDGFs have been extensively characterized at the molecular and cellular level and in in vivo model systems. This, in turn, has lead to an increasing number of PDGF-based therapies designed to accelerate or combat defects in tissue repair. This review aims to summarize recent developments in the role of PDGF in key mesenchymal cell functions. Many of the current developments in this field have primarily focused on advancements in understanding cell differentiation, migration, proliferation and the development of emerging PDGF-based therapies and hence will be primary focus of this review.

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“…Research on the application of tissue growth factors for promoting periodontal regeneration is still receiving increasing attention [3]. Platelet-derived growth factor (PDGF) is extensively used both in vitro and in vivo oral wound healing models, either alone [4][5][6][7] or in combination with other agents such as insulin-like growth factor-1 (IGF-1) [8,9], extracellular matrix molecules [10], lysophosphatidic acid [11] and/or with other different agents [12]. PDGF influences migration, proliferation and synthetic activity of periodontal ligament (PDL) fibroblast cells [5,13,14].…”

Section: Introductionmentioning

confidence: 99%

Effect of PDGF-BB combined with EDTA gel on adhesion and proliferation to the root surface

et al. 2012

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Periodontal regeneration using EDTA or PDGF showed promising results, but the effect of combined application was still unclear. This study aimed to verify the effect of EDTA and/or PDGF application on root adhesion and proliferation of PDL fibroblast cells. Eighty specimens were prepared from forty periodontitis teeth and made five groups: (1) diseased (untreated), (2) SRP (scaling root planing), (3) EDTA (24%), (4) PDGF (25 ng/ml) and (5) Combined application of EDTA and PDGF. Periodontal ligament cells were cultured on the above conditioned dentin plate, and SEM examination was preformed and cells were counted within a representative standard area for both cell morphology and density. All groups including untreated showed significantly increase of adhered cells from baseline to 7 days. Among them, rate of increase was much higher in EDTA, PDGF, and combined groups. ANOVA test indicated that the number of cells in PDGF and combined groups was significantly higher than diseased group at 1 day. On day 7, PDGF and combined groups showed significantly higher number of adhesion cells than that found in the diseased, SRP and EDTA groups. Thus, root conditioning with EDTA enhanced cell adhesion more than SRP alone. There was no significant difference of cell number between PDGF and combined group. Combined application of EDTA and PDGF increased significantly PDL cell adhesion than EDTA alone. PDGF alone, however, also showed comparable effect to combined application at all periods. Thus, synergistic effect between PDGF and EDTA was not observed.

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Lysophosphatidic Acid Modulates the Healing Responses of Human Periodontal Ligament Fibroblasts and Enhances the Actions of Platelet‐Derived Growth Factor

Abstract: 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.

Cited by 13 publications

References 47 publications

Lysophosphatidic acids, cyclic phosphatidic acids and autotaxin as promising targets in therapies of cancer and other diseases.

Lysophosphatidic acids, cyclic phosphatidic acids and autotaxin as promising targets in therapies of cancer and other diseases.

Platelet-derived growth factor signaling in mesenchymal cells

Effect of PDGF-BB combined with EDTA gel on adhesion and proliferation to the root surface

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