Transcriptomics

Dataset Information

44

Priming integrin alpha5 promotes human mesenchymal stromal cell osteoblast differentiation and osteogenesis


ABSTRACT: Human adult mesenchymal stromal cells (hMSC) have the potential to differentiate into chondrogenic, adipogenic or osteogenic lineages, providing a potential source for tissue regeneration. An important issue for efficient bone regeneration is to identify factors that can be targeted to promote the osteogenic potential of hMSCs. Using transcriptomic analysis, we found that integrin alpha5 (ITGA5) expression is upregulated during dexamethasone-induced hMSCs osteoblast differentiation. Gain-of-function studies showed that ITGA5 promotes the expression of osteoblast phenotypic markers as well as in vitro osteogenesis in hMSCs. Downregulation of endogenous ITGA5 using shRNA blunted osteoblast marker expression and osteogenic differentiation. Pharmacological and molecular analyses showed that the enhanced hMSCs osteoblast differentiation induced by ITGA5 was mediated by activation of FAK/ERK1/2-MAPKs and PI3K signaling pathways. Remarkably, activation of ITGA5 using a specific antibody that primes the integrin or a peptide that specifically activates ITGA5 was sufficient to enhance ERK1/2-MAPKs and PI3K signaling and to promote osteoblast differentiation and osteogenic capacity of hMSCs. We also demonstrate that hMSCs engineered to over-express ITGA5 exhibited a marked increase in their osteogenic potential in vivo. These findings not only reveal that ITGA5 is required for osteoblast differentiation of adult human MSCs but also provide a novel targeted strategy using ITGA5 agonists to promote the osteogenic capacity of hMSCs, which may be used for tissue regeneration in bone disorders where the recruitment or capacity of MSCs is compromised. Keywords: Time course of osteogenic differentiation processes Overall design: Gene expression profiles were generated from bone marrow MSC before and 1, 3 and 7 days after stimulation with 10E-7M dexamethasone to study the early molecular processes of osteogenic differentiation. 3 replicates per timepoint.

REANALYSED by: GSE20125E-GEOD-49910

INSTRUMENT(S): [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array

ORGANISM(S): Homo sapiens  

SUBMITTER: Thomas Häupl  

PROVIDER: GSE18043 | GEO | 2009-09-10

SECONDARY ACCESSION(S): PRJNA119295

REPOSITORIES: GEO

Similar Datasets

2009-01-01 | S-EPMC2773973 | BioStudies
2009-09-18 | E-GEOD-18043 | ArrayExpress
1000-01-01 | S-EPMC3129223 | BioStudies
2019-01-01 | S-EPMC6829495 | BioStudies
1000-01-01 | S-EPMC5330439 | BioStudies
2019-01-01 | S-EPMC6410690 | BioStudies
2015-01-01 | S-EPMC4700155 | BioStudies
1000-01-01 | S-EPMC5079670 | BioStudies
2020-01-01 | S-EPMC7539212 | BioStudies
2016-01-01 | S-EPMC5018671 | BioStudies