1The loss of proteoglycan (PG) is regarded as one of the early signs of osteoarthritis (OA), 2 thus observing the progress of PG loss would be useful for the early detection of OA. In 3 this study, high-frequency ultrasound was used to monitor and analyze the trypsin-4 induced progressive degeneration in articular cartilage. Full-thickness cartilage-bone 5 specimens (n = 10) prepared from normal bovine patellae were digested using 0.25% 6 trypsin solution for different periods of time to evaluate the dynamic of the digestion 7 process. The trypsin penetration front was observed in M-mode image, which was 8 acquired using a nominal 50 MHz focused transducer. The transient speed of the 9 digestion process was estimated from the image. The digestion fraction, which represents 10 the ratio of the digestion depth to the total cartilage thickness, was estimated from 11 ultrasound data and histology sections. With ultrasound, the digestion fraction observed 12 in the 10 specimens ranged from 64 to 99%, and was correlated to that measured by 13 histology (R 2 0.63, p<0.05). It was found that the digestion speed decreased nonlinearly 14 with depth from 0.61 ± 0.16 m/s (mean ± SD) in the superficial zone to 0.04 ± 0.02 15 m/s in a region located at 70% of the cartilage thickness in depth. The relationship 16 between the digestion depth and the exposure duration in trypsin could be described 17 using a 3 rd order polynomial function. The full-thickness of digested and undigested 18 tissues was also measured using caliper, estimated from ultrasound data and histology 19 sections, and compared. These findings indicate that ultrasound could provide useful 20 information about the trypsin-induced progressive PG depletion in articular cartilage. 21Therefore, ultrasound represents a useful tool to evaluate the dynamic of models of OA in 22 vitro in cartilage specimens in a research environment, and this would ultimately help the 23 in-vitro examination of articular cartilage for research related to model of OA from the 24 early stages of tissue degradation. 25