Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
An in Vitro Model of Human Tenocytes to Investigate the Effectiveness of a Novel Formulation for the Prophylaxis and Treatment of Tendinopathies
Torrent1, Anna, Ruhi1, Ramon, Martinez2, Cristina, Cid2, Mar, Csaki3, Constanze, Shakibaei3, Mehdi
Clinically, tendinopathies pose a major problem as they require lengthy treatment protocols and the tendon often heals unsatisfactorily. Tendons have a limited capacity for self-repair due to low cell density and little mitotic activity. Pro-inflammatory cytokines such as interleukin-1b (IL-1b) 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 effectiveness of a novel formulation (BIS-033) including mucopolysaccharides, in an in vitro model of tendon inflammation.
In monolayer cultures primary human tenocytes were either treated with BIS-033, non-stimulated or stimulated with IL-1b, stimulated with IL-1b and BIS-033 or pre-stimulated with BIS-033 followed by co-treatment with BIS-033 and IL-1b. Cell viability, adhesion, proliferation and production of ECM were analysed with light microscopy and transmission electron microscopy (TEM). Immunofluorescence was used to evaluate production of type I collagen, the main extracellular matrix protein produced by tenocytes. We also studied the expression of the signal transduction and adhesion molecule b1-integrin. Western blotting (WB) was performed to evaluate expression of apoptotic and inflammatory markers (MMP-1, Cox-2, Caspase-3).
BIS-033 had a potent stimulatory effect on human tenocyte proliferation and ECM production. BIS-033 was able to suppress the catabolic, apoptotic and inflammatory effects induced by IL-1b in human tenocytes. This was demonstrated by the suppression of IL-1b-induced expression of MMP-1, Cox-2 and Caspase-3 and up-regulation of type I collagen and b1-integrin.
The methodology and results demonstrate that this in vitro model is useful for evaluating the potential effectiveness of new compounds and formulations on tendon disorders. The results presented also suggest that this formulation inhibits catabolic and inflammatory processes in an in vitro model of tendonitis. BIS-033 may therefore be used on prophylaxis and treatment of tendinopathies to stimulate tendon healing, regeneration and repair.
To cite this abstract, please use the following information:
Torrent, Anna, Ruhi, Ramon, Martinez, Cristina, Cid, Mar, Csaki, Constanze, Shakibaei, Mehdi; An in Vitro Model of Human Tenocytes to Investigate the Effectiveness of a Novel Formulation for the Prophylaxis and Treatment of Tendinopathies [abstract]. Arthritis Rheum 2009;60 Suppl 10 :85