RESUMEN
Brain-derived neurotrophic factor (BDNF) enhances periodontal tissue regeneration. Tissue regeneration is characterized by inflammation, which directs the quality of tissue repair. The objective of this study is to propose the relevance of BDNF to inflammation. In this study, we investigated the effect of BDNF on intercellular adhesion molecule (ICAM)-1, which is an inflammatory marker, expressed in interleukin (IL)-1ß-treated human microvascular endothelial cells (HMVECs). In addition, we studied the effect of BDNF on the adhesion of neutrophil-like differentiated HL-60 cells to HMVECs in a cell adhesion assay. We demonstrated that BDNF attenuates the IL-1ß-induced ICAM-1 mRNA and protein expression. Treatment of HMVECs with IL-1ß led to an increase in the number of adherent neutrophil-like HL-60 cells. BDNF significantly decreased the number of neutrophil-like HL-60 cells attached to HMVECs. In conclusion, BDNF may reduce excess inflammation through reduced neutrophil recruitment by regulating ICAM-1 expression.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/farmacología , Expresión Génica/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1beta/farmacología , Western Blotting , Adhesión Celular/efectos de los fármacos , Línea Celular , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Células HL-60 , Humanos , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular/genética , Microvasos/citología , Neutrófilos/citología , Neutrófilos/inmunología , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
We recently demonstrated that brain-derived neurotrophic factor (BDNF) promotes periodontal tissue regeneration. The purpose of this study was to establish an essential component of a rational approach for the clinical application of BDNF in periodontal regenerative therapy. Here, we assessed the sequence of early events in BDNF-induced periodontal tissue regeneration, especially from the aspect of cementum regeneration. Brain-derived neurotrophic factor was applied into experimental periodontal defects in Beagle dogs. The localization of cells positive for neurotrophic tyrosine kinase, receptor, type 2, proliferating cell nuclear antigen, osteopontin, integrin αVß3, and integrin α2ß1 was evaluated by immunohistochemistry. The effects of BDNF on adhesion of cultured human periodontal ligament cells was examined by an in vitro study. The results suggest that BDNF could induce rapid cementum regeneration by stimulating adhesion, proliferation, and differentiation of periodontal ligament cells in the early regenerative phase, resulting in enhancement of periodontal tissue regeneration.
Asunto(s)
Periodoncio , Animales , Factor Neurotrófico Derivado del Encéfalo , Cemento Dental , Perros , Humanos , Ligamento Periodontal , RegeneraciónRESUMEN
This study aimed to observe the regenerative effect of brain-derived neurotrophic factor (BDNF) in a non-human primate furcation defect model. Class II furcation defects were created in the first and second molars of 8 non-human primates to simulate a clinical situation. The defect was filled with either, Group A: BDNF (500 µg/ml) in high-molecular weight-hyaluronic acid (HMW-HA), Group B: BDNF (50 µg/ml) in HMW-HA, Group C: HMW-HA acid only, Group D: empty defect, or Group E: BDNF (500 µg/ml) in saline. The healing status for all groups was observed at different time-points with micro computed tomography. The animals were euthanized after 11 weeks, and the tooth-bone specimens were subjected to histologic processing. The results showed that all groups seemed to successfully regenerate the alveolar buccal bone, however, only Group A regenerated the entire periodontal tissue, i.e., alveolar bone, cementum and periodontal ligament. It is suggested that the use of BDNF in combination with a scaffold such as the hyaluronic acid in periodontal furcation defects may be an effective treatment option.