PDK2 promotes chondrogenic differentiation of mesenchymal stem cells by upregulation of Sox6 and activation of JNK/MAPK/ERK pathway
Braz. j. med. biol. res
;
50(2): e5988, 2017. graf
Artigo
em Inglês
| LILACS
| ID: biblio-839254
ABSTRACT
This study was undertaken to clarify the role and mechanism of pyruvate dehydrogenase kinase isoform 2 (PDK2) in chondrogenic differentiation of mesenchymal stem cells (MSCs). MSCs were isolated from femurs and tibias of Sprague-Dawley rats, weighing 300-400 g (5 females and 5 males). Overexpression and knockdown of PDK2 were transfected into MSCs and then cell viability, adhesion and migration were assessed. Additionally, the roles of aberrant PDK2 in chondrogenesis markers SRY-related high mobility group-box 6 (Sox6), type ΙΙ procollagen gene (COL2A1), cartilage oligomeric matrix protein (COMP), aggrecan (AGC1), type ΙX procollagen gene (COL9A2) and collagen type 1 alpha 1 (COL1A1) were measured by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The expressions of c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and extracellular regulated protein kinase (ERK) were measured. Overexpressing PDK2 promoted cell viability, adhesion and inhibited cell migration in MSCs (all P<0.05). qRT-PCR assay showed a potent increase in the mRNA expressions of all chondrogenesis markers in response to overexpressing PDK2 (P<0.01 or P<0.05). PDK2 overexpression also induced a significant accumulation in mRNA and protein expressions of JNK, p38MAPK and ERK in MSCs compared to the control (P<0.01 or P<0.05). Meanwhile, silencing PDK2 exerted the opposite effects on MSCs. This study shows a preliminary positive role and potential mechanisms of PDK2 in chondrogenic differentiation of MSCs. It lays the theoretical groundwork for uncovering the functions of PDK2 and provides a promising basis for repairing cartilage lesions in osteoarthritis.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Proteínas Serina-Treonina Quinases
/
Condrogênese
/
Sistema de Sinalização das MAP Quinases
/
Proteínas Quinases JNK Ativadas por Mitógeno
/
Fatores de Transcrição SOXE
/
Células-Tronco Mesenquimais
Limite:
Animais
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2017
Tipo de documento:
Artigo
País de afiliação:
China
Instituição/País de afiliação:
Tianjin Medical University/CN
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