Anti-inflammatory and anti-catabolic effects of TENDOACTIVE® on human tenocytes in vitro
M. Shakibaei1, C. Buhrmann1 and A. Mobasheri2
1Musculoskeletal Research Group, Institute of Anatomy, Ludwig-Maximilian-University Munich, Munich, Germany and 2Musculoskeletal Research Group, School of Veterinary Medicine and Science, Faculty of Medicine and Health Sciences, University of Nottingham, Sutton Bonington, United Kingdom.
Offprint requests to: Prof. Dr. Mehdi Shakibaei, Ludwig-Maximilian-University Munich, Institute of Anatomy, Musculoskeletal Research Group, Pettenkoferstrasse 11, D-80336 Munich, Germany. e-mail: firstname.lastname@example.org
Summary. Tendons have a limited capacity for self-repair due to the low density and mitotic activity of tenocytes. Pro-inflammatory cytokines such as interleukin-1ß (IL-1ß) have been identified as the main initiators of tendinopathies, stimulating inflammation, apoptosis and extracellular matrix (ECM) degradation. The aim of this study was to evaluate the potential of Tendoactive®, a newly developed proprietary nutraceutical formulation that includes mucopolysaccharides, collagen and vitamin C, in an in vitro model of tendon inflammation. The effects of Tendoactive® were studied in primary cultures of human tenocytes treated with IL-1ß for up to 72 h. Expression of collagen type I, integrin ß1, cyclo-oxygenase-2 (COX-2), caspase-3 and matrix metalloproteinase-1 (MMP-1) was monitored by western blotting. The effects of Tendoactive® on the expression, phosphorylation and nuclear translocation of protein components of the NF-κB system were studied by western blotting and immunofluorescence respectively. Treatment of tenocytes with Tendoactive® suppressed IL-1ß-induced NF-κB activation and p65 nuclear translocation. These events correlated with down-regulation of NF-κB targets including COX-2, MMP-1 and activated caspase-3. Tendoactive® also reversed the IL-1ß-induced down-regulation of collagen type I and ß1-integrin receptor expression. These results indicate that Tendoactive® has nutraceutical potential as an anti-inflammatory agent for treating tendinopathy through suppression of NF-κB mediated IL-1ß catabolic signalling pathways in tenocytes. Histol Histopathol 26, 1173-1185 (2011)
Key words: Tendon, Tenocyte, Tendinopathy, NF-κB, IL-1ß, MMP, COX-2, Tendoactive®, Anti-inflammatory, Nutraceutical formulation