Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Novel Treatment of Tendinopathies with a Sulfated Disaccharide of Hyaluronic Acid-Promising In Vitro Results.
Torrent1, Anna, Ruhi1, Ramon, Alaez1, Carlos, Buhrmann2, Constanze, Shakibaei3, Mehdi
As tendons regenerate slowly and inefficiently after trauma, tendinopathies pose a serious musculoskeletal problem. Recent studies indicate that initiators of tendinopathy include a number of pro-inflammatory cytokines such as Interleukin-1b (IL-1b), which are known to enhance and support inflammation and promote apoptosis through the production of cyclooxygenase-2 (Cox-2), metalloproteinases (MMPs) and activation of caspase-3. The aim of this study was to evaluate the potential prophylactic and/or regenerative effects of a sulphated disaccharide of hyaluronic acid (methyl 2-acetamido-106-deoxi-106-O-(b-D-glucopyranosyluronic acid)-4,6-di-sulfo-a-D-glucopyranoside, trisodium salt), BIS014, on suppression of catabolic, inflammatory and apoptotic pathways in IL-1b stimulated human tenocytes in vitro.
Monolayer cultures of primary human tenocyes were pre-stimulated with BIS014 followed by co-treatment with IL-1b and BIS014 and evaluated with electron microscopy and western blotting. Control cultures were left untreated or treated with IL-1b or BIS014. Cell viability, adhesion, proliferation and production of extracellular matrix (ECM) were analysed with light microscopy and transmission electron microscopy. Immunofluorescence was used to evaluate production of type I collagen, the main extracellular matrix protein synthesized by tenocytes. Immunoblotting was performed to determine expression of type I collagen, b-1 integrins, caspase-3, Cox-2 and MMP-1, -9 and -13.
Ultrastructural evaluation with electron microscopy demonstrated that BIS014 exerts a potent stimulatory effect on human tenocyte proliferation and was able to suppress catabolic, apoptotic and inflammatory effects induced by IL-1b. Suppression of IL-1b-induced up-regulation of activated caspase-3, Cox-2 and MMP-1, -9 and -13 by western blotting further confirmed these results.
These results demonstrate that the synthetic disaccharide of hyaluronic acid BIS014 may have therapeutic utility for the healing, regeneration and repair of tendons.
To cite this abstract, please use the following information:
Torrent, Anna, Ruhi, Ramon, Alaez, Carlos, Buhrmann, Constanze, Shakibaei, Mehdi; Novel Treatment of Tendinopathies with a Sulfated Disaccharide of Hyaluronic Acid-Promising In Vitro Results. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :106