gms | German Medical Science

Objective: When diseased or injured, adult tendons do not heal to the same regenerative capacity of embryonic tissue, but exhibit a highly disorganized matrix that consequently affects normal tissue function. Disorganized collagen bundles and variations in the diameters and orientation of the collagen fibers are characteristics of a tendinopathic tendon. The mechanical properties of tendon are, to a great extent, determined by the molecular structure and organization of the collagen fibers. The maintenance of the tendon matrix has important consequences for the ability of the tendon to resist mechanical forces and to repair response to injury.

The aim of this study was to investigate the effect of Tendoactive^® (TA) on fibrillogenesis of collagen and on Tenomodulin levels in the presence/absence of IL-1β in a 3-dimensional culture of primary human tenocytes.

Material/Methods: Primary human tenocytes were cultured in high density cultures [1] for 0, 7, 10 and 14 days under the different treatments. Cultures were either treated with TA, non-stimulated or stimulated with IL-1β, and stimulated with IL-1β and TA. Tendoactive (TA) is a nutraceutical formulation that contains mainly mucopolysaccharides.

Tendon ultrastructure, in particular extracellular matrix (ECM) and collagen fibril organization and orientation, was investigated by electron microscopy. Additionally, we evaluated by western blot analysis if the treatment of tenocytes with the formulation could prevent IL-1β-induced upregulation of catabolic events leading to downregulation of production of matrix specific proteins such as the glycoprotein Tenomodulin. This protein is described in literature [2] that plays a role in tendon development and organization of the tendinous structure.

Results: Cells treated with IL-1β underwent apoptosis and extracellular matrix was completely disorganized. The treatment with Tendoactive^® was able to counteract the negative effects on the tenocytes: cells looked healthy and with abundant and well organized extracellular matrix (ECM) consisting of thick fibrils of collagen. Also tenocytes displayed high amount of euchromatin that indicates that cells are very active and with a high rate of protein biosynthesis.

Western blot demonstrated a considerable prophylactic effect of Tendoactive^® on human tenocytes co-treated with IL-1β on Tenomodulin production. Additionally an anabolic effect of the formulation was observed: cells showed an increased Tenomodulin production compared to the untreated control cells.

Conclusion: These results indicate that Tendoactive^® could be useful in the prevention and/or treatment of tendinopathies (tendinitis, tendinosis, etc). The administration of this product is believed to contribute to remodelling the tendon, which is a necessary step in returning it to its mature functional structure.