RESUMO
Prolyl-hydroxyproline (Pro-Hyp) is one of the major constituents of collagen-derived dipeptides. The objective of this study was to investigate the effects of Pro-Hyp on the proliferation and differentiation of MC3T3-E1 osteoblastic cells. Addition of Pro-Hyp did not affect MC3T3-E1 cell proliferation and matrix mineralization but alkaline phosphatase activity was significantly increased. Furthermore, cells treated with Pro-Hyp significantly upregulated gene expression of Runx2, Osterix, and Col1α1. These results indicate that Pro-Hyp promotes osteoblast differentiation. This study demonstrates for the first time that Pro-Hyp has a positive effect on osteoblast differentiation with upregulation of Runx2, Osterix, and Collα1 gene expression.
Assuntos
Diferenciação Celular/fisiologia , Colágeno/metabolismo , Dipeptídeos/fisiologia , Osteoblastos/citologia , Células 3T3 , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica , Proliferação de Células , Colágeno Tipo I/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Dipeptídeos/metabolismo , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Fator de Transcrição Sp7 , Fatores de Transcrição/genéticaRESUMO
Mangiferin is a polyphenolic compound present in Salacia reticulata. It has been reported to reduce bone destruction and inhibit osteoclastic differentiation. This study aimed to determine whether mangiferin directly affects osteoblast and osteoclast proliferation and differentiation, and gene expression in MC3T3E1 osteoblastic cells and osteoclastlike cells derived from primary mouse bone marrow macrophage cells. Mangiferin induced significantly greater WST1 activity, indicating increased cell proliferation. Mangiferin induced significantly increased alkaline phosphatase staining, indicating greater cell differentiation. Reverse transcriptionpolymerase chain reaction (RTPCR) demonstrated that mangiferin significantly increased the mRNA level of runtrelated transcription factor 2 (RunX2), but did not affect RunX1 mRNA expression. Mangiferin significantly reduced the formation of tartrateresistant acid phosphatasepositive multinuclear cells. RTPCR demonstrated that mangiferin significantly increased the mRNA level of estrogen receptor ß (ERß), but did not affect the expression of other osteoclastassociated genes. Mangiferin may inhibit osteoclastic bone resorption by suppressing differentiation of osteoclasts and promoting expression of ERß mRNA in mouse bone marrow macrophage cells. It also has potential to promote osteoblastic bone formation by promoting cell proliferation and inducing cell differentiation in preosteoblast MC3T3E1 cells via RunX2. Mangiferin may therefore be useful in improving bone disease outcomes.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoclastos/citologia , Osteoclastos/efeitos dos fármacos , Xantonas/farmacologia , Animais , Biomarcadores , Células da Medula Óssea/citologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Linhagem Celular , Linhagem da Célula/efeitos dos fármacos , Linhagem da Célula/genética , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Perfilação da Expressão Gênica , Masculino , Camundongos , Osteoblastos/metabolismo , Osteoclastos/metabolismoRESUMO
[reaction: see text] A novel 2-pyridone synthesis via nucleophilic addition of malonic esters to alkynyl imines has been developed. The reaction of dialkylalkyl sodiomalonates with alkynyl imines provided 2-pyridones in good to excellent yields.