Type I collagen homotrimer alters tail tendon material properties.

Abstract

Type I collagen homotrimer is associated with age-related musculoskeletal, cardiovascular and fibrotic diseases - in addition to cancer - due to over-production of the alpha-1(I) chain from COL1A1, or inactivation of COL1A2. Type I collagen homotrimer in the osteogenesis imperfecta model oim does not cause bone fragility but exacerbates the oim phenotype. Here Col1a2 null and oim tail tendons were analysed to elucidate the role of collagen homotrimer in soft collagenous tissues. In Col1a2 null homozygotes, tendon diameter was reduced at 8 weeks old, whilst at 18 and 52 weeks old maximum modulus and hysteresis strain energy density were reduced and strain at maximum modulus was increased. Failure strain increased at 52 weeks. Oim homozygotes had additional changes in tendon diameter at 18 weeks, with narrower collagen fibrils and reduced hysteresis strain energy density at 8 weeks old, and reduced percentage hysteresis at both ages. There was evidence of type I collagen homotrimer in Col1a2 null heterozygotes, which had significant but less pronounced changes in failure strain, strain at maximum modulus and hysteresis strain energy at 18 weeks than homozygotes. Proteomics identified altered matrix protein composition in Col1a2 null and oim homozygotes whilst tissue fluorescence increased in Col1a2 null homozygotes at 52 weeks. Hence homotrimeric type I collagen affects the material properties and matrix protein composition of tail tendon following adolescence, whilst the oim mutation introduces earlier and additional alterations to energy dissipation. STATEMENT OF SIGNIFICANCE: Type I collagen is normally a heterotrimeric molecule but homotrimers can also be formed. To study how type I collagen homotrimer affects tissues, genetic inactivation of Col1a2 in mice was used to study the effect on tail tendon biomechanics and protein composition. Tendons comprising solely homotrimeric collagen displayed altered biomechanical properties that were more pronounced at older ages, indicative of damage accumulation or adaptive responses. An altered protein composition indicates both compensatory over-production and corresponding loss of other matrix proteins that may modulate tissue biomechanics. Findings in heterozygotes indicate that even partial homotrimer production is sufficient to alter tendon properties and provides insight into the tissue-level consequences of musculoskeletal and cardiovascular disease associated with type I collagen homotrimer production.