RESUMEN
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. Migration responses were measured using a microchemotaxis chamber. GF and PDLF intracellular Ca(2+) mobilization responses to multiple LPA species and LPAR subtype-specific agonists were measured by using a cell-permeable fluorescent Ca(2+) indicator dye. RESULTS: LPA stimulated ERK1/2 phosphorylation via LPA(1)(-3). For GFs, LPA(1) preferentially elicited chemotaxis, and LPA(1-3) for PDLFs, as confirmed using subtype-specific agonists. Elevation of intracellular calcium seems to be mediated through LPA(1) and LPA(3), with little, if any, contribution from LPA(2). CONCLUSIONS: To the best of our knowledge, this study provides the first evidence that LPA signals through specific LPAR subtypes to stimulate human oral fibroblast regenerative responses. These data, in conjunction with our previous findings showing that LPA modulates GF and PDLF responses to PDGF, suggest that LPA is a factor of emerging importance to oral wound healing.
Asunto(s)
Encía/fisiología , Lisofosfolípidos/fisiología , Ligamento Periodontal/fisiología , Receptores del Ácido Lisofosfatídico/clasificación , Regeneración/fisiología , Adulto , Western Blotting , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/fisiología , Células Cultivadas , Quimiotaxis/efectos de los fármacos , Quimiotaxis/fisiología , Femenino , Fibroblastos/efectos de los fármacos , Fibroblastos/fisiología , Colorantes Fluorescentes , Encía/citología , Encía/efectos de los fármacos , Humanos , Isoxazoles/farmacología , Lisofosfolípidos/farmacología , Masculino , Proteína Quinasa 1 Activada por Mitógenos/efectos de los fármacos , Proteína Quinasa 1 Activada por Mitógenos/fisiología , Proteína Quinasa 3 Activada por Mitógenos/efectos de los fármacos , Proteína Quinasa 3 Activada por Mitógenos/fisiología , Organotiofosfatos/farmacología , Ligamento Periodontal/citología , Ligamento Periodontal/efectos de los fármacos , Ácidos Fosfatidicos/farmacología , Fosforilación , Propionatos/farmacología , Receptores del Ácido Lisofosfatídico/agonistas , Receptores del Ácido Lisofosfatídico/antagonistas & inhibidores , Transducción de Señal/fisiología , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiología , Adulto JovenRESUMEN
Dental procedures done in the vicinity of dermal fillers may result in complications of the dermal fillers such as infections which may mimic a dental infection. These infections of dermal fillers must be differentiated from facial cellulitis or from dental infection as treatment for infection from dermal fillers may be prolonged with repeated use of antibiotics, incision and drainage or removal of the filler material itself. Dental surgeons need to be aware of this potential risk in order to recognize and manage it appropriately.