Dataset Information

Exendin-4 promotes the osteogenic differentiation of osteoblasts via the Hedgehog/Gli1 signaling pathway.

ABSTRACT: This study aimed to investigate the effect and mechanisms of Exendin-4 mediated-Hedgehog/Gli1 signaling pathway on the differentiation of osteoblasts in mouse. The alkaline phosphate activity, alizarin red staining and expression of Gli1, GLP-1R, Hedgehog, Runx2 and osteocalcin were analyzed using PCR and Western blot analysis after treating the osteoblastic cell line MC3T3-E1 with Exendin-4. Osteoblasts were treated with Gli1-siRNA and Hedgehog receptor antagonist Cyclopamine (Cy) and analyzed for their impact on the Hedgehog/Gli1 signaling pathway. Our results showed that optimal treatment of Exendin-4 was 7 days at 10-7 mol/L. Exendin-4 significantly promoted osteoblast formation in the cell line in a dose-dependent manner and up-regulated the expression of GLP-1R, Hedgehog and Gli1. Gli1-siRNA significantly down regulated the expression of Gli1 and Runx2, and offset Exendin-4-induced osteoblast differentiation. Similarly, Cy offset Exendin-4-induced Gli1 up-regulation. It is clear that Exendin-4 can promote the osteogenic differentiation of osteoblasts through Hedgehog/Gli1 signaling pathway.

SUBMITTER: Gao L

PROVIDER: S-EPMC5801369 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Exendin-4 promotes the osteogenic differentiation of osteoblasts via the Hedgehog/Gli1 signaling pathway.

Gao Liu L Li Shilun S Li Yukun Y

American journal of translational research 20180115 1

This study aimed to investigate the effect and mechanisms of Exendin-4 mediated-Hedgehog/Gli1 signaling pathway on the differentiation of osteoblasts in mouse. The alkaline phosphate activity, alizarin red staining and expression of Gli1, GLP-1R, Hedgehog, Runx2 and osteocalcin were analyzed using PCR and Western blot analysis after treating the osteoblastic cell line MC3T3-E1 with Exendin-4. Osteoblasts were treated with Gli1-siRNA and Hedgehog receptor antagonist Cyclopamine (Cy) and analyzed ...[more]

PMID: 29423016

Similar Datasets

Project description:ObjectivesTo investigate the potential role of Ribosomal protein L35 (RPL35) in regulating chondrocyte catabolic metabolism and to examine whether osteoarthritis (OA) progression can be delayed by overexpressing RPL35 in a mouse compression loading model.MethodsRNA sequencing analysis was performed on chondrocytes treated with or without 20 % elongation strain loading for 24 h. Experimental OA in mice was induced by destabilization of the medial meniscus and compression loading. Mice were randomly assigned to a sham group, an intra-articular adenovirus-mediated overexpression of the negative group, and an intra-articular adenovirus-mediated overexpression of the RPL35 operated group. The Osteoarthritis Research Society International score was used to evaluate cartilage degeneration. Immunostaining and western blot analyses were conducted to detect relative protein levels. Primary mouse chondrocytes were treated with 20 % elongation strain loading for 24 h to investigate the role of RPL35 in modulating chondrocyte catabolic metabolism and regulating cellular senescence in chondrocytes.ResultsThe protein expression of RPL35 in mouse chondrocytes was significantly reduced when excessive mechanical loading was applied, while elevated protein levels of RPL35 protected articular chondrocytes from degeneration. In addition, the RPL35 knockdown alone induced chondrocyte senescence, decreased the expression of anabolic markers, and increased the expression of catabolic markers in vitro in part through the hedgehog (Hh) pathway.ConclusionsThese findings demonstrated a functional pathway important for OA development and identified intra-articular injection of RPL35 as a potential therapy for OA prevention and treatment.The translational potential of this articleIt is necessary to develop new targeted drugs for OA due to the limitations of conventional pharmacotherapy. Our study explores and demonstrates the protective effect of RPL35 against excessive mechanical stress in OA models in vivo and in vitro in animals. These findings might provide novel insights into OA pathogenesis and show its translational potential for OA therapy.

Dataset Information

Exendin-4 promotes the osteogenic differentiation of osteoblasts via the Hedgehog/Gli1 signaling pathway.

Publications

Exendin-4 promotes the osteogenic differentiation of osteoblasts via the Hedgehog/Gli1 signaling pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets