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Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells.
Wang, Chen-Xi; Ge, Xi-Yuan; Wang, Ming-Yue; Ma, Ting; Zhang, Yu; Lin, Ye.
Afiliação
  • Wang CX; Department of Implantology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, Pe
  • Ge XY; Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, 100081, People's Republic of China.
  • Wang MY; Department of Implantology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, Pe
  • Ma T; Department of Implantology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, Pe
  • Zhang Y; Department of Implantology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, Pe
  • Lin Y; Department of Implantology, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, 100081, Pe
Stem Cell Res Ther ; 11(1): 12, 2020 01 03.
Article em En | MEDLINE | ID: mdl-31900224
BACKGROUND: Osteogenic differentiation of bone mesenchymal stem cells (BMSCs) is regulated by numerous signaling pathways. Dopamine (DA), a neurotransmitter, has previously been demonstrated to induce new bone formation by stimulating the receptors on BMSCs, but the essential mediators of DA-induced osteogenic signaling remain unclear. METHODS: In this work, we evaluated the influence of both dopamine D1 and D2 receptor activation on BMSC osteogenic differentiation. Gene and protein expression of osteogenic-related markers were tested. The direct binding of transcriptional factor, Runx2, to those markers was also investigated. Additionally, cellular differentiation-associated signaling pathways were evaluated. RESULTS: We showed that the expression level of the D1 receptor on BMSCs increased during osteogenic differentiation. A D1 receptor agonist, similar to DA, induced the osteogenic differentiation of BMSCs, and this phenomenon was effectively inhibited by a D1 receptor antagonist or by D1 receptor knockdown. Furthermore, the suppression of protein kinase A (PKA), an important kinase downstream of the D1 receptor, successfully inhibited DA-induced BMSC osteogenic differentiation and decreased the phosphorylation of ERK1/2. Compared with P38, MAPK, and JNK, DA mainly induced the phosphorylation of ERK1/2 and led to the upregulation of Runx2 transcriptional activity, thus facilitating BMSC osteogenic differentiation. On the other hand, an ERK1/2 inhibitor could reverse these effects. CONCLUSIONS: Taken together, these results suggest that ERK signaling may play an essential role in coordinating the DA-induced osteogenic differentiation of BMSCs by D1 receptor activation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteogênese / Células da Medula Óssea / Receptores de Dopamina D1 / Sistema de Sinalização das MAP Quinases / Células-Tronco Mesenquimais Limite: Animals / Humans Idioma: En Revista: Stem Cell Res Ther Ano de publicação: 2020 Tipo de documento: Article País de publicação: Reino Unido
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteogênese / Células da Medula Óssea / Receptores de Dopamina D1 / Sistema de Sinalização das MAP Quinases / Células-Tronco Mesenquimais Limite: Animals / Humans Idioma: En Revista: Stem Cell Res Ther Ano de publicação: 2020 Tipo de documento: Article País de publicação: Reino Unido