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http://purl.uniprot.org/citations/32061523http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Objectives

To investigate the functional effect of implicated variants within BGN and COL5A1 on gene expression of components of the extracellular matrix (ECM) in a TGF-β-stimulated risk model for musculoskeletal soft tissue injuries.

Design

Experimental research, laboratory study.

Methods

Skin biopsies were obtained from nine healthy participants with either a combined increased or reduced risk profile for COL5A1 rs12722 C>T and BGN rs1126499 C>T - rs1042103 G>A, and primary fibroblast cell lines were established. Total RNA was extracted at baseline (10% FBS), after serum starvation (1% FBS) and TGF-β1 treatment (1% FBS, 10ng/mL TGF-1β). Relative mRNA levels of BGN, COL5A1, DCN and VEGFA was quantified using Taqman® array pre-spotted plate assays (Applied Biosystems, Foster city, CA, USA).

Results

At baseline, the reduced risk group had 2.5, 1.9 and 2 fold increases (p<0.001) in relative BGN, COL5A1 and VEGFA mRNA levels respectively. In the serum starved experiments, except for a significant 1.5 fold (p=0.017) increase in relative DCN mRNA expression in the reduced risk group, similar observations were noted for the other three genes. After TGF-1β treatment, the reduced risk group had 1.3 (p=0.011) and 1.4 fold (p=0.001) increases in the relative COL5A1 and VEGFA mRNA levels, respectively.

Conclusions

Altered mRNA levels associated with genetic risk profiles for musculoskeletal soft injury risk at baseline (BGN, COL5A1 and VEGFA), with serum starvation (DCN) and after TGF-β1 treatment (COL5A1 and VEGFA) provide additional functional evidence to support the association of implicated genetic loci with several musculoskeletal soft tissue injuries. Implication of altered gene expression profiles underpinning these genetic risk associated loci potentially highlight key therapeutic targets for management of these injuries."xsd:string
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http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/author"Collins M."xsd:string
http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/author"Prince S."xsd:string
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http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/author"Willard K."xsd:string
http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/author"Laguette M.N."xsd:string
http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/author"Alves de Souza Rios L."xsd:string
http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/author"D'Alton C."xsd:string
http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/name"J Sci Med Sport"xsd:string
http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/pages"695-700"xsd:string
http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/title"Altered expression of proteoglycan, collagen and growth factor genes in a TGF-beta1 stimulated genetic risk model for musculoskeletal soft tissue injuries."xsd:string
http://purl.uniprot.org/citations/32061523http://purl.uniprot.org/core/volume"23"xsd:string
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