Evaluation Of Effects Of Wnt Pathway Inhibitor On Osteoarthritis In Rabbits By Multimodal Imaging Study

Objective To evaluate the injury of cartilage and subchondral bone in rabbit knee osteoarthritis(OA)model and to explore the therapeutic effect of Wnt signal pathway inhibitor SM04690 on OA cartilage and subchondral bone by multimodal imaging method.Materials and methods 45 New Zealand white rabbits were randomly divided into three groups:(1)treatment group(n=15): were established osteoarthritis models of the right knee by modified Hulth method,and received SM04690(5μg / 0.2ml)by intra-articular injection two weeks after operation;(2)experimental group(n=15): were established osteoarthritis models of the right knee by modified Hulth method,and received vehicle(0.2ml)by intra-articular injection two weeks after operation;(3)control group(n=15): were operated to open the knee joint without any treatment and received vehicle(0.2ml)by intra-articular injection two weeks after operation.At the time of 4,8 and 12 weeks after operation,5 animals in each group were randomly selected for dual-energy CT and MRI.Finally,the animals were killed and the knee joints were dissected.The samples were fixed and dried for SR-μCT scanning and histological examinationResult(1)Imaging quantitative parameters: At the time of 4,8 and 12 weeks after operation,calcium density(CAD),contrast media(CM),bone volume fraction(BV/TV)and trabecular thickness(TB.Th)measured in the experimental group were lower than those in the control group,and were lower than those in the treatment group,respectively(P<0.05).The T2 value measured in the experimental group was higher than that in the control group,and was higher than that in the treatment group;that in the treatment group was higher than that in the control group,respectively(P<0.05).In the cartilage thickness measurement of femoral condyle,tibial plateau and the average of knee joint,there was no significant difference between each two groups at the time of 4 weeks after operation,respectively(P > 0.05);at the time of 8 and 12 weeks,those measured in the experimental group were lower than those in the control group,and were also lower than those in the treatment group,respectively(P<0.05).(2)Imaging of chondrocytes showed by SR-μCT: In the treatment group,at the time of 4 weeks after operation,the chondrocytes were arranged in order and the surface of cartilage was smooth;at the time of 8weeks,the chondrocytes were slightly disordered,and the surface of cartilage was slightly rough;at the time of12 weeks,the chondrocytes arranged disorderly,the surface of cartilage was rough,and cartilage microcracks were formed.In the experimental group,at the time of 4weeks after operation,chondrocytes were arranged in order and the surface of cartilage was slightly rough;at the time of 8weeks,chondrocytes were arranged disordered,and the surface of cartilage was rough;at the time of 12 weeks,chondrocytes were arranged disordered,the surface fibrillations appeared,the deep fissures associated,and the subchondral bone was exposed.In the control group,chondrocytes were arranged orderly and the cartilage surface was smooth.(3)Histological staining results: In the treatment group,at the time of 4 weeks after operation,the cartilage structure was complete,part of the cartilage surface was slightly irregular;at the time of 8 weeks,the cartilage surface was slightly rough,the number of chondrocytes increased,and the arrangement was still orderly;at the time of 12 weeks,the cartilage surface was fibrotic,the microcracks on the cartilage surface were formed.in the experimental group,at the time of 4 weeks after operation,the surface of cartilage was slightly rough and the number of chondrocytes was slightly increased;at the time of8 weeks,the surface of cartilage was abraded,the cracks on the surface of cartilage were formed;at the time of 12 weeks,the surface of cartilage was severely abraded,the cracks were enlarged and widened,the subchondral bone was exposed.in the control group,the surface of cartilage was smooth and the arrangement of chondrocytes was orderly;The Mankin score of the experimental group in each period was lower than that of the control group,and was lower than that of the treatment group,respectively(P<0.05).There was no significant difference in Mankin score between the treatment group and the control group at 4 weeks after operation(P>0.05).At the time of 8and 12 weeks after operation,the Mankin score of the treatment group was higher than that of the control group,respectively(P<0.05).Conclusion Wnt signal pathway inhibitor SM04690 has a positive effect on cartilage and subchondral bone of the rabbit knee osteoarthritis model.Multimodal imaging plays an important role in early diagnosis and curative effect evaluation of OA.