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ObjectivesOsteoarthritis (OA) is a degenerative joint disease, which is characterized by destruction of articular cartilage. It seriously affects the quality of life and has very high disability rate. Currently there are a lot of conservative therapies for OA, but for their limitation they can not fundamentally change the natural course of OA. At present, artificial joint replacement is still the most effective method for the treatment of osteoarthritis, however this treatment may bring about a series of problems, such as age restrictions, great surgical injury, many complications, high cost, a second renovation and so on. Therefore, it is vital to look for an effective conservative treatment to delay or prevent the progress of osteoarthritis. By applying hyaluronic acid (HA) to prepare cartilage-derived morphogenetic protein (CDMP-1) to maintain effective drug concentrations within the joint, this experiment observed its role in inhibiting OA progress and effect on the expression of MMP-13 and TIMP-1, and probed into the continuous treatment mechanism of CDMP-1 to OA of rabbit knee joint.MethodsForty healthy adult New Zealand white rabbits were randomly selected as the control group 8 no experimental intervention, and the remaining 32 rabbits as the experimental group were treated with experimental intervention. By randomly checking, the experimental group of 32 rabbits were randomly numbered, followed by extraction number divided into 4 groups, n = 8, respectively, the model group, HA microspheres (HA-M), CDMP-1 solution group (CDMP-1-S), HA/CDMP-1 microspheres (HA/CDMP-1-M).1,4,7 in the experimental process, the first day, in the rabbit knee joint cavity after the injection of double-papain solution modeling. HA coated with CDMP-1 Preparation of sustained release microspheres lyophilized. After modeling the first 3 weeks and 6 weeks, all experimental groups were injected with 1ml of rabbit articular saline, 1ml CDMP-1 solution, 1ml PBS containing microspheres, 1ml with CDMP-1 microspheres, in the first 9 weeks rats were killed. India’s score compared with the general cartilage damage in each group;, HE staining and PAS staining pathological changes compared rickets, the use of Mankin score evaluation; application of RT-PCR, MMP-13, TIMP-1 mRNA expression changes.ResultsFirst, the appearance and the release characteristics of microspheres. Round appearance of HA microspheres, particle size distribution, most of the microspheres in the 1-10μm particle size distribution range. HA/CDMP-1-M faster initial release, especially in the first 24 hours of drug release of 25% of the total, followed by a smooth gradual drug release, the release of 7 days to 40%.Second, the INK score results of each group. Compared with the control group, model group was significantly increased articular cartilage damage; CDMP-1-S group and the PBS-M as compared with the model group, no significant articular cartilage damage mitigation; CDMP-1-M group of articular cartilage damage Than the model group was significantly reduced.Third, the Mankin score results of each group. Compared with the control group, model group was significantly increased articular cartilage damage; CDMP-1-S group and the PBS-M as compared with the model group, no significant articular cartilage damage mitigation; CDMP-1-M group of articular cartilage damage Than the model group was significantly reduced.Last, the expression changes of articular cartilage MMP-13 and TIMP-1mRNA. Compared with the control group, model group, MMP-13 mRNA expression was increased, TIMP-1mRNA expression was significantly decreased; CDMP-1-S group and the PBS-M group of MMP-13, TIMP-1mRNA expression and no significant difference between the model group; CDMP-1-M group than in model group, MMP-13 mRNA expression was significantly decreased, TIMP-1 mRNA expression was significantly increased.Conclusions1.Intra-articular injection with HA/CDMP-1-M can promote cartilage repairation and inhibit the progress of osteoarthritis;Meanwhile, microsphere delivery system is an important security for the effective treatment of osteoarthritis with CDMP-1.2. The treatment of osteoarthritis with HA/CDMP-1-M is achieved by increased expression of TIMP and reduced expression of MMP.3. Through intra-articular injection of papain, model of knee osteoarthritis can be successfully established.
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