Impact of an oral amino acid provision on Achilles peritendinous amino acid concentrations in young and older adults

ABSTRACTRecent studies have indicated that consumption of amino acid-rich compounds can increase tendon collagen content and enhance biomechanical function. Still, it is not clear as to what extent oral consumption of amino acids alters peritendinous amino acid concentrations. Whether aging alters the delivery of amino acids to tendon tissue after oral consumption is also not known. Using microdialysis, we determined the impact of a single oral essential amino acid bolus on Achilles peritendinous amino acid concentrations in younger (n=7; 27±1 yr.) and older adults (n=6; 68±2 yrs.) over four hours. The peritendinous concentration of all amino acids in the beverage except methionine (p=0.136) and glycine (p=0.087) increased with time (p<0.05). Additionally, the concentrations of glycine and arginine were greater in older adults (p≤0.05). We also accessed the impact of amino acid consumption on peritendinous concentrations of pro-collagen Iα1, a marker of collagen synthesis. Pro-collagen Iα1 tended to change with time (p=0.071) but was not altered age (p=0.226). We demonstrate that an oral amino acid bolus leads to modest increases in Achilles peritendinous amino acid concentrations in young and older adults. The concentration of some amino acids was also greater in older adults. However, the amino acid bolus did not significantly impact peritendinous pro-collagen concentrations.

Age-related changes in the physical properties, cross-linking, and glycation of collagen from mouse tail tendon

Collagen is a structural protein whose internal cross-linking critically determines the properties and functions of connective tissue. Knowing how the cross-linking of collagen changes with age is key to understanding why the mechanical properties of tissues change over a lifetime. The current scientific consensus is that collagen cross-linking increases with age and that this increase leads to tendon stiffening. Here, we show that this view should be reconsidered. Using MS-based analyses, we demonstrated that during aging of healthy C57BL/6 mice, the overall levels of collagen cross-linking in tail tendon decreased with age. However, the levels of lysine glycation in collagen, which is not considered a cross-link, increased dramatically with age. We found that in 16-week-old diabetic db/db mice, glycation reaches levels similar to those observed in 98-week-old C57BL/6 mice, while the other cross-links typical of tendon collagen either decreased or remained the same as those observed in 20-week-old WT mice. These results, combined with findings from mechanical testing of tendons from these mice, indicate that overall collagen cross-linking in mouse tendon decreases with age. Our findings also reveal that lysine glycation appears to be an important factor that contributes to tendon stiffening with age and in diabetes.

Targeted pathological collagen delivery of sustained-release rapamycin to prevent heterotopic ossification

Heterotopic ossification (HO) in connective tissues like tendons and ligaments severely damages tissue structure. The pathogenesis of HO remains unclear but may involve mTOR. The results presented here indicate that tendon stem/progenitor cells do not undergo osteochondrogenic differentiation when mTOR signaling is inactivated by gene knockout or rapamycin (RAPA) treatment. Meanwhile, it is necessary to deliver RAPA to the injured sites and avoid disturbing the normal tendon. A RAPA delivery system, developed using collagen hybrid peptide (CHP) to modify the surface of poly(lactic-co-glycolic acid) (PLGA) nanoparticles, targeted RAPA specifically to pathological tendon collagen. The CHP-PLGA-RAPA nanoparticles showed excellent pathological collagen affinity, sustained-release ability, and bioactivity. In a mouse model of tendon HO, CHP-PLGA-RAPA nanoparticles specifically bound to pathological tendon and strongly suppressed HO progression. The mTOR signaling pathway appears to be a viable therapeutic target for tendon HO, and CHP-PLGA nanoparticles may be valuable for the treatment of tendon-related diseases.

A Horse of a Different Color?: Tensile Strength and Elasticity of Sloth Flexor Tendons

Tendons must be able to withstand the tensile forces generated by muscles to provide support while avoiding failure. The properties of tendons in mammal limbs must therefore be appropriate to accommodate a range of locomotor habits and posture. Tendon collagen composition provides resistance to loading that contributes to tissue strength which could, however, be modified to not exclusively confer large strength and stiffness for elastic energy storage/recovery. For example, sloths are nearly obligate suspenders and cannot run, and due to their combined low metabolic rate, body temperature, and rate of digestion, they have an extreme need to conserve energy. It is possible that sloths have a tendon “suspensory apparatus” functionally analogous to that in upright ungulates, thus allowing for largely passive support of their body weight below-branch, while concurrently minimizing muscle contractile energy expenditure. The digital flexor tendons from the fore- and hindlimbs of two-toed (Choloepus hoffmanni) and three-toed (Bradypus variegatus) sloths were loaded in tension until failure to test this hypothesis. Overall, tensile strength and elastic (Young’s) modulus of sloth tendons were low, and these material properties were remarkably similar to those of equine suspensory “ligaments.” The results also help explain previous findings in sloths showing relatively low levels of muscle activation in the digital flexors during postural suspension and suspensory walking.