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Objective: It has remained ambiguous as to whether oral dosing of glucosamine (GlcN) would make its way to the joint and affect changes in the cartilage, particularly the integrity of cartilage and chondrocyte function. The objective of this study was to trace the fate of orally dosed GlcN and determine definitively if GlcN was incorporated into cartilage proteoglycans., Design: Two dogs were treated with (13)C-GlcN-HCl by oral dosing (500 mg/dog/d for 2 weeks and 250 mg/dog/d for 3 weeks). Cartilage was harvested from the tibial plateau and femoral condyles along with tissue specimens from the liver, spleen, heart, kidney, skin, skeletal muscle, lung, and costal cartilage. Percentages of (13)C and (13)C-GlcN present in each tissue sample were determined by inductively coupled plasma mass spectroscopy (ICP-MS) and nuclear magnetic resonance spectroscopy, respectively., Results: In the case of dog 1 (2-week treatment), there was an increase of 2.3% of (13)C present in the articular cartilage compared to the control and an increase of 1.6% of (13)C in dog 2 compared to control. As to be expected, the highest percentage of (13)C in the other tissues tested was found in the liver, and the remaining tissues had percentages of (13)C less than that of articular cartilage., Conclusion: The results are definitive and for the first time provide conclusive evidence that orally given GlcN can make its way through the digestive tract and be used by chondrocytes in joint cartilage, thereby potentially having an effect on the available GlcN for proteoglycan biosynthesis.