RESUMO
Photobiomodulation (PBM) therapy displays relevant properties for tissue healing and regeneration, which may be of interest for the tissue engineering field. Here, we show that PBM is able to improve cell survival and to interact with recombinant human Bone Morphogenetic Protein 4 (rhBMP4) to direct and accelerate odonto/osteogenic differentiation of dental derived mesenchymal stem cells (MSCs). MSCs were encapsulated in an injectable and thermo-responsive cell carrier (Pluronic® F-127) loaded with rhBMP4 and then photoactivated. PBM improved MSCs self-renewal and survival upon encapsulation in the Pluronic® F-127. In the presence of rhBMP4, cell odonto/osteogenic differentiation was premature and markedly improved in the photoactivated MSCs. An in vivo calvarial critical sized defect model demonstrated significant increase in bone formation after PBM treatment. Finally, a balance in the reactive oxygen species levels may be related to the favorable results of PBM and rhBMP4 association. PBM may act in synergism with rhBMP4 and is a promise candidate to direct and accelerate hard tissue bioengineering.
Assuntos
Proteína Morfogenética Óssea 4/administração & dosagem , Portadores de Fármacos , Terapia com Luz de Baixa Intensidade/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos da radiação , Poloxâmero/química , Engenharia Tecidual/métodos , Alicerces Teciduais , Adolescente , Adulto , Animais , Proteína Morfogenética Óssea 4/química , Regeneração Óssea , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Autorrenovação Celular/efeitos dos fármacos , Autorrenovação Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células Cultivadas , Humanos , Hidrogéis , Injeções , Lasers Semicondutores , Terapia com Luz de Baixa Intensidade/instrumentação , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Camundongos Nus , NF-kappa B/metabolismo , Osteogênese/efeitos dos fármacos , Osteogênese/efeitos da radiação , Osso Parietal/lesões , Osso Parietal/patologia , Osso Parietal/cirurgia , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo , Adulto JovemRESUMO
Both BMP2 and BMP4 are involved in tooth development. We examined phenotypes and BMP2 and BMP4 gene variations in two Mexican oligodontia families. Physical and oral examinations and panoramic radiographs were performed on affected and unaffected members in these two families. The affected members lacked six or more teeth. DNA sequencing was performed to detect BMP2 and BMP4 gene variations. Three single nucleotide polymorphisms (SNPs) in BMP2 and BMP4 genes were identified in the two families, including one synonymous and two missense SNPs: BMP2 c261A>G, pS87S, BMP2 c570A>T, pR190S, and BMP4 c455T>C, pV152A. Among the six affected patients, 67% carried "GG" or "AG" genotype in BMP2 c261A>G and four were "TT" or "AT" genotype in BMP2 c570A>T (pR190S). Polymorphism of BMP4 c455T>C resulted in amino acid changes of Val/Ala (pV152A). BMP2 c261A>G and BMP4 c455T>C affect mRNA stability. This was the first time that BMP2 and BMP4 SNPs were observed in Mexican oligodontia families.