Second Place

Background:Statins (HMG-CoA Reductase inhibitors) reduce the incidence and progression of osteoarthritis of the knee. Nitrogen-containing bisphosphonates (N-BPs) and statins have similar mechanisms of action, but the effects of N-BPs on articular cartilage in osteoarthritis are not understood. We sought to determine if the bisphosphonate alendronate (ALN) has anti-inflammatory effects on articular chondrocytes in vitro.Methods:An in vitro model was developed for sustaining harvested rat chondrocytes in an alginate gel matrix. Using this model with human chondrocytes, osteoarthritis was simulated using interleukin- 1 beta (IL-1 beta) stimulation. Cells were treated with ALN (10100 mM) and IL-1 beta (0.01 and 0.1 ng/mL) for 24 and 48 h. RNA was isolated to quantify the effects of IL-1 beta and ALN on chondrocyte gene expression for cartilage matrix synthesis (aggrecan, collagen type I and II) and degradation (MMP13, ADAMTS4, ADAMTS5).Results:Collagen type I, collagen type II, and aggrecan expression decreased with IL-1 beta stimulation in human chondrocytes, which was not reversed by ALN treatments. MMP13, ADAMTS4, and ADAMTS5 expression increased with IL-1 beta stimulation, and the increases in MMP13 and ADAMTS5 were reduced by ALN treatments after 24 h.Conclusions:ALN reversed increases in chondrocyte MMP13 and ADAMTS5 expression due to IL-1 beta stimulation in vitro, and ALN may play a role in preventing cartilage matrix degradation in osteoarthritis.