The Effect Of Tougu Xiaotong Capsule On The Structure Of Cartilage And Subchondral Bone In Osteoporotic Osteoarthritis Of The Knee In Rabbits

ObjectiveOsteoporotic osteoarthritis is a kind of special osteoarthritis(OA).Our clinical and basic research shows that Tougu Xiaotong Capsule,a traditional Chinese medicine for tonifying the kidney,has a better curative effect on OA.Therefore,this research used the Tougu Xiaotong Capsule to interfere with osteoporotic OA model,observe its effect on structural changes of cartilage and subchondral bone,analyze the mechanism of the drug,and to provide the foundational research basis for the application of the drug in the prevention and treatment of osteoporotic OA.MethodsForty eight New Zealand rabbits randomly selected 18 as control group,and the rest 30 rabbits were modeled using castration and modified Hulth methods to establish an osteoporotic OA model.After five weeks,from osteoporotic OA model and control group randomly selected 6 rabbits,respectively,and the model was identified by observing the pathological changes of cartilage and subchondral bone.The remaining 24 osteoporotic OA rabbits were randomly divided into the model group and the traditional Chinese medicine group,12 in each group.The control group and the model group were given intragastric administration of normal saline,and the traditional Chinese medicine group was given intragastric administration of the aqueous solution of Tougu Xiaotong Capsule.The animals were sacrificed in batches after gavage for 4 weeks or 8 weeks,each group took 6 rabbits.The femur was taken to make paraffin sections.HE staining and safranin-O fast green staining were used to observe the changes of cartilage.Cartilage injury was assessed using Mankin's score and the course of OA was staged.After the surface of the tibial plateau was been observed,Micro-CT scan was performed to observe the changes of tibial plateau,sagittal plane of subchondral bone and cross section of subchondral bone,and measured trabecular bone parameters.The subtle structure changes of subchondral bone were observed by scanning electron microscopy.The expression of inflammatory cytokines IL-1? and TNF-? was detected.The changes of serum bone metabolic markers of ALP,TRAP,OPG,and RANKL were detected.ResultsAfter 5 weeks of modeling,the cartilage surface of the model group was damaged,the cartilage matrix staining was severely decreased,and the Mankin score was significantly higher than the control group.Subchondral osteophyte hyperplasia,trabecular structure damage,bone density was significantly reduced.This shows that the osteoporotic OA model was successfully established.After 4 weeks of treatment,the cartilage structure in the traditional Chinese medicine group was improved,the cartilage surface was smoother,and the cartilage matrix staining was deepened.The Mankin score was significantly lower than the control group;the osteophyte was reduced,the density of trabecular bone was higher and the spacing of trabecular bone was smaller,and the connection was good.IL-1? and TNF-? were significantly lower than those in the model group.The activity of ALP and TRAP in the traditional Chinese medicine group was significantly lower than that in the model group,and the OPG/RANKL ratio was significantly higher than that in the model group.It shows that the traditional Chinese medicine can improve the structure of cartilage and subchondral bone,reduce the level of inflammatory factors,regulate the rate of bone remodeling,and reduce the pathological process of the early and middle stage of osteoporotic OA.After 8 weeks of treatment,although the improvement of structure of cartilage and subchondral bone was not as good as the traditional Chinese medicine group for 4 weeks of morphological.The levels of inflammatory factors and bone metabolism in the Chinese medicine group were significantly lower than those in the model group.This indicated that the drug partially improved the structure of cartilage and subchondral bone of osteoporotic OA in the middle and late stage,reduced the level of inflammatory factors,and regulated the rate of bone remodeling.Conclusion1.In the pathological process of osteoporotic OA,cartilage structure damage and subchondral bone loosening are important structural changes.Subchondral osteoporosis may promote the cartilage structure damage and aggravate the pathological process of osteoporotic OA.2.Tougu Xiaotong Capsule can reduce the degradation of cartilage matrix by reducing the level of inflammatory factors,and at the same time promote the synthesis and secretion of proteoglycan in chondrocytes,reduce the destruction of articular cartilage,and delay cartilage degeneration.3.Chinese medicine may improve bone mass and improve the microstructure of subchondral bone trabeculae by regulating bone metabolism.4.This study suggests that Tougu Xiaotong Capsule can be used for the treatment of osteoporotic OA,and the early application in osteoporotic OA is helpful to delay the progression of the disease.