Altered expression of proteoglycan, collagen and growth factor genes in a TGF-ß1 stimulated genetic risk model for musculoskeletal soft tissue injuries.

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-ß-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-ß1 treatment (1% FBS, 10ng/mL TGF-1ß). 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-1ß 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-ß1 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.

Are TNC gene variants associated with anterior cruciate ligament rupture susceptibility?

OBJECTIVES: To investigate the role of inter-individual variations in a particular glycoprotein, TNC, and its potential contribution to anterior cruciate ligament (ACL) injury susceptibility in Polish Caucasian participants. ACL rupture is one of the most prevalent and severe knee injury that predominantly occurs during sports participation, primarily via a non-contact mechanism. Several polymorphisms in genes encoding glycoproteins either independently or as allelic combinations, modulate the risk of musculoskeletal soft tissue injuries. Specifically, the TNC rs1330363 (C>T), rs2104772 (T>A) and rs13321 (G>C) variants, independently or in haplotype combinations, were analysed in this context. DESIGN: Case-control genetic association study. METHODS: A group of 421 physically active, unrelated participants were recruited where 229 individuals with surgically diagnosed primary ACL rupture and 192 apparently healthy participants without any history of ACL injuries. Participants were genotyped for the above variants. RESULTS: Genotype and allele frequencies of TNC variants did not differ between cases and controls. Haplotype analysis revealed no association between TNC and predisposition to ACL rupture. CONCLUSIONS: Our analyses did not reveal a significant association between these TNC variants and risk of ACL rupture in Polish Caucasian participants.