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Adiponectin And Adiponectin Antibody Effect Of Chitosan Hydrogel By Osteoarthritis

Posted on:2013-10-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:W X WangFull Text:PDF
GTID:1264330401456093Subject:Clinical Medicine
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Background and aims:Osteoarthritis (OA) is a chronic degenerative joint disease of the synovial joint.OA is frequent in elder population,it is already one of the ten most disabling diseases in developed countries. For some patients, there is nothing to do but to receive an arthroplasty surgery. To date, etiopathogenesis of OA is still unclear. Recent studies show that mechanical stress caused cartilage distruction can only partly explain the association between obesity and OA, adipokines secreted in over-weight people may play an important pathophysiologic role. Through the studies of etiopathogenesis of OA, we may find important target factors, which contributes to effective non-surgery treatment of OA. This research includes two parts:part1. Investigate the effect of adiponectin and adiponectin monoclonal antibody on chondrocytes. Part2. Prepare chitosan/glycerophosphate (CS/GP) thermo-sensitive hydrogel and evaluate cytotoxicity of the hydrogel.Methods:Stimulate the chondrocytes with adiponectin and adiponectin monoclonal antibody, then detect the expression of IL-6and type II collagen by Real-time fluorescence quantitative PCR. Prepare the CS/GP thermo-sensitive hydrogel, study the thermo-sensitive characteristics, evaluate the cytotoxicity by CCK-8method.Results:Part1. Adiponectin(1μg/ml) up-regulates the IL-6amount by110times compared to the control(p<0.001). After changing the culture medium, the IL-6amount decreased distinctly, which indicates that adiponectin could induce the expression of IL-6by chondrocytes. Adiponectin monoclonal antibody slightly increased the IL-6. In the group which include equal amount of adiponectin and adiponectin monoclonal antibody, the IL-6amount shows no difference compared to the group include the adiponectin alone. This result might indicate that adiponectin monoclonal antibody did not block the bonding between adiponectin and adiponectin receptor. Another possibility is that the amount of antibody is far from sufficient to neutralize the adiponectin. The quantification of type Ⅱ collagen indicates that adiponectin reduced the collagen production, meanwhile the antibody increased the collagen production. Part2. By mixing different amount of CS and GP, we obtained the thermo-sensitive hydrogel under physiological temperature. The gelling temperature drops and the gelling time shortened as the GP amount increase. After co-cultivation with different amount of CS/GP hydrogel, the chondrocytes show slow proliferation, and the cell viability show slow increase at the beginning, in the second half of the cultivation, the viability decreased slightly. Conclusion:Part1. Adiponectin could induce the IL-6expression, reduce the type II collagen, indicates that adiponectin may contribute in the destruction of cartilage in the OA progression. Adiponectin monoclonal antibody may promote the collagen production, thus promote the cartilage matrix formation. Part2. CS/GP hydrogel has thermo-sensitive characteristic under physiological temperature. When co-cultivated with the hydrogel, chondrocytes showed growth and proliferation, which indicates the potential of hydrogel to be used as drug release system in the intra-articular injection.
Keywords/Search Tags:adiponectin, adiponectin monoclonal antibody, osteoarthritis, chitosan, thermo-sensitive hydrogel
PDF Full Text Request
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