Dataset Information

Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells.

ABSTRACT:

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.

SUBMITTER: Wang CX

PROVIDER: S-EPMC6942280 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells.

Wang Chen-Xi CX Ge Xi-Yuan XY Wang Ming-Yue MY Ma Ting T Zhang Yu Y Lin Ye Y

Stem cell research & therapy 20200103 1

<h4>Background</h4>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.<h4>Methods</h4>In this work, we evaluated the influence of both dopamine D1 and D2 receptor activation on BMSC osteogenic differentiation. Gene and protein ...[more]

PMID: 31900224

Similar Datasets

Project description:BackgroundGlobally, bone fractures are the most common musculoskeletal trauma, and approximately 8-10% of cases that fall into the categories of delayed or non-union healing. To date, there are no efficient pharmacological agents to accelerate the healing of bone fractures. Thus, it is necessary to find new strategies that accelerate bone healing and reduce the incidence of non-union or delayed fracture healing. Previous studies have revealed that the plasminogen activation system has been demonstrated to play an important role in bone metabolism. However, the function of SERPINB2 in the osteogenesis of hBMSCs remains unclear. Therefore, in this study, we investigated the effects and mechanism of SERPINB2 on osteogenic differentiation.MethodsWe investigated the osteogenesis effects of hBMSCs by both exogenous SerpinB2 protein and SERPINB2 gene silencing in vitro. Cell proliferation assay was used to assess the effect of exogenous SerpinB2 or SERPINB2 silencing on proliferation of hBMSCs. qPCR and Western blotting analysis detected the expression of target genes and proteins respectively. ALP staining was used to evaluated ALP activity and Alizarin Red staining (ARS) was used to evaluate mineral deposition. In vivo, a murie tibial fracture model was established, histological evaluation and radiographic analysis was used to confirm the therapeutic effects of SERPINB2 silencing in fracture healing. Statistical significance between two groups was determined by Student's t test, one-way ANOVA or Bonferroni's post-hoc test according to the distribution of the tested population.ResultsThe addition of exogenous SerpinB2 protein inhibted osteoblast differentiation of hBMSCs in vitro, while SERPINB2 gene silencing significant promote osteoblast differentiation of hBMSCs in vitro. And silenced SERPINB2 gene also increased mineral deposits. Moreover, β-catenin levels were up-regulated by SERPINB2 gene depletion. And the enhancement of osteogenic differentiation induced by SERPINB2 silencing was almost inhibited by specific Wnt/β-catenin signaling pathway inhibitor. In a murine tibial fracture model, local injection of SERPINB2 siRNA improved bone fracture healing.ConclusionsTaken together, these findings indicate that SERPINB2 silencing promoted osteogenic differentiation of BMSCs via the Wnt/β-catenin signaling pathway, and silenced SERPINB2 in vivo effectively promotes fracture healing, suggesting that SERPINB2 may be a novel target for bone fracture healing.

Dataset Information

Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells.

Background

Methods

Results

Conclusions

Publications

Dopamine D1 receptor-mediated activation of the ERK signaling pathway is involved in the osteogenic differentiation of bone mesenchymal stem cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets