Altered expression of proteoglycan, collagen and growth factor genes in a TGF-β1 stimulated genetic risk model for musculoskeletal soft tissue injuries

Abstract 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, 10 ng/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  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.