Experinental Study On Effect Of Curcumin On Knee Osteoarthritis In Rabbits By Intra-peritoneal Injection

Background:Osteoarthritis (OA) is the most common form of arthritis and one of themost primary cause of chronic disability. Knee and hip joints are the mostfrequently involved joints.The incidence of OA is based on the combinedeffects of mechanical and biological factors, which made destruction of thenormal synthesis and degradation coupled in articular cartilage cells,extracellular matrix, and subchondral bone . OA is caused by a variety offactors and these factors change the performance of the cartilage cells andextracellular matrix in morphology, biochemistry, molecular biology andbiomechanics. These changes lead to softening of the articular cartilage,fibrosis, ulcers, lack of subchondral bone sclerosis and eburnation andosteophyte formation and subchondral cystic degeneration and deteriorationof articular cartilage is a hallmark of OA pathogenesis. Although the preciseaetiology of this disease is still unknown，but it is clear that A variety ofcytokines participate in the formation of osteoarthritis through altering thebalance of articular cartilage matrix catabolism and anabolism. Such as thepyrolysis effect of matrix metalloproteinases (MMPs) on the cartilage matrixmolecule (including collagen type II and proteoglycans) and high expressionof IL-1 in OA cartilage mediated inflammatory reactions. Recent studies havefound that Curcumin The main component of turmeric has the effects ofanti-inflammatory and immunomodulatory. Curcumin can intervene in theexpression of a variety of inflammatory cytokines such as tumor necrosis factor, IL-1, IL-6 and has a protective effect on OA. The objective of ourstudy was to investigate the effcts of curcumin intraperitoneal injection onknee osteoarthritis in rabbits to found probably a new effective therapeuticmethod for OA.Objective:（1）To establish the rabbit model of knee osteoarthritis.（2）To observe the pathological changes of the joints of animal models.（3）To investigate the effects of Curcumin on cytokines in theperipheral blood of experimental animals.（4）To investigate the histological changes of the articular cartilage ofexperimental animals.Methods:（1）The right knee of rabbits were straight by gypsum for six weeks toestablish animal model of osteoarthritis. Then the rabbits were randomlydivided into two groups including injection of 0.9%NaCl and curcumin. Therewas another No-treatment control group.（2）The rabbits in curcumin group was intraperitoneally injected bycurcumin 50mg/(kg.d) for two weeks .After treatment ,all animals weresacrificed to collect blood serum and articular cartilage of knee.（3）The tissue slices were stained by HE and Safranin O to explorepathological analysis and evaluation by Mankin score of cartilage specimens.（4）The level of IL-1β, IL-6, IL-17, MCP-1, MMP13, KS in serumwere measured by ELISA.（5）The expression of TNF-α, type II collagen and MMP9 in cartilagespecimens were detected by immunohistochemistry. Results:（1）The rabbit knee osteoarthritis model was induced successfully andconfirmed histological evaluation.（2）Mankin scores of groups increased by degrees from normal group,curcumin group to arthritis group ,the differences among the groups werestatistically significant（p<0.05）.（3）The level of IL-1β, IL-6, IL-17, MMP13, KS in serum increasedfrom normal group, curcumin group to arthritis group ,the differences amongthe groups were statistically significant（p<0.05）.（4）The expression of TNF-α, type II collagen and MMP9 in cartilagespecimens increased from normal group, curcumin group to arthritis group.Conclusion:（１）Our study confirmed that using gypsum for straight fixed rabbitknee joint is a feasible method to build animal model of osteoarthritis.（2）The increased expression of IL-1β, TNF-α, IL-6, IL-17, MMP9 andMMP13 in cartilage cells and peripheral blood of arthritis group confirmedthat these cytokines may be involved in the destruction of the cartilage cellsand matrix degradation through a variety of signaling pathways.（3）Curcumin have the effects of anti-inflammatory andimmunomodulatory. Curcumin can intervene in the expression of a variety ofcytokines,and inhibite of the destruction of the cartilage cells and cartilagematrix degradation. Curcumin can be probably a new effective therapeuticmethod for OA.