Topical administration of the nitric oxide donor glyceryl trinitrate modifies the structural and biomechanical properties of ovine articular cartilage

Objective: To examine the effect of topical administration of glyceryl trinitrate (GTN), an exogenous nitric oxide (NO) donor, on the structural and biomechanical properties of uncalcified articular cartilage (UCC) in aged ewes. Design: Twelve ewes were used for this study. Six of these were treated with 2% GTN ointment (0.7 mg/kg) twice per week (GTN), and the remaining six were used as normal controls (NOC). After sacrifice at 26 weeks, dynamic biomechanical indentation testing and thickness determination (by needle penetration) were performed on tibial plateau articular cartilage at 18 locations. Using histological sections prepared from the lateral and medial femoral condyles (LFC, MFC) and tibial plateau (LTP, MTP), the thickness of UCC, cartilage proteoglycan content (intensity of toluidine blue staining; LFC, MFC only), and collagen birefringence (LTP, MTP, LFC only) were quantified by computer-assisted image analysis. Results: Phase lag of tibial plateau cartilage was reduced in GTN sheep relative to NOC (mean of all testing locations 11.0±1.9° vs 12.1±2.3°; P=0.0001). GTN treatment also globally reduced UCC thickness across the joint (ANOVA for all measured zones, P<0.0001). UCC thinning was most pronounced in the MFC (P=0.025) and LTP (P=0.0002). Proteoglycan content was reduced in the MFC (P=0.019), while collagen birefringence, was increased in superficial cartilage zones of the LTP. Conclusions: NO donation via topical administration of GTN to normal ewes reduced the thickness and phase lag of femoro-tibial articular cartilage, suggesting a disturbance in chondrocyte metabolism. Regional alterations of collagen organisation and proteoglycan content were consistent with this interpretation.