Lysylhydroxylation and non-reducible crosslinking of human supraspinatus tendon collagen: changes with age and in chronic rotator cuff tendinitis

Objectives-To investigate age related and site specific variations in turno ver and chemistry of the collagen network in healthy tendons as well as the role of collagen remodelling in the degeneration of the supraspinatus tend on (ST-D) in rotator cuff tendinitis. Methods-Collagen content and the amount of hydroxylysine (Hyl), hydroxylysy lpyridinoline (HP), lysylpyridinoline (LP), and the degree of non-enzymatic glycation (pentosidine) were investigated in ST-D and in normal human supr aspinatus (ST-N) and biceps brachii tendons (BT-N) by high-performance liqu id chromatography. Results-In BT-N, tendons that served as control tissue as it shows rarely m atrix abnormalities, pentosidine levels rise linearly with age (20-90 years ), indicating little tissue remodelling (resulting in an undisturbed accumu lation of pentosidine). A similar accumulation was observed in ST-N up to 5 0 years. At older ages, little pentosidine accumulation was observed and pe ntosidine levels showed large interindividual variability. This was interpr eted as remodelling of collagen in normal ST after age 50 years because of microruptures (thus diluting old collagen with newly synthesised collagen). All degenerate ST samples showed decreased pentosidine levels compared wit h age matched controls, indicating extensive remodelling in an attempt to r epair the tendon defect. Collagen content and the amount of Hyl, HP, and LP of ST-N and BT-N did not change with age. With the exception of collagen c ontent, which did not differ, all parameters were significantly (p<0.001) l ower in BT-N. The ST-D samples had a reduced collagen content and had highe r Hyl, HP, and LP levels than ST-N (p<0.001). Conclusions-Inasmuch as Hyl, HP, and LP levels in ST-N did not change with age, tissue remodelling as a consequence of microruptures does not seem to affect the quality of the tendon collagen. On the other hand, the clearly d ifferent profile of post-translational modifications in ST-D indicates that the newly deposited collagen network in degenerated tendons is qualitative ly different. It is concluded that in ST-D the previously functional and ca refully constructed matrix is replaced by aberrant collagen. This may resul t in a mechanically less stable tendon; as the supraspinatus is constantly subjected to considerable forces this could explain why tendinitis is mostl y of a chronic nature.