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Hyaluronic acid-chitosan nanoparticles encoding CrmA attenuate interleukin-1β induced inflammation in synoviocytes
Bo Qiu1, Xiong-Feng Xu1, Rong-Hui Deng1
1Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Abstract:
Osteoarthritis (OA) is a common degenerative joint disease characterized by inflammation of synoviocytes and degradation of cartilage. In the present study, hyaluronic acid/chitosan (HA/CS) nanoparticles were used as a vehicle for gene therapy of OA, and the cytokine response modifier A (CrmA) pDNA was proposed as the target gene. The HA/CS/pCrmA nanoparticles were prepared and the characteristics of the nanoparticles were examined. The nanoparticles were spherical, and the smallest size was obtained with the HA:CS weight ratio of 1:4. The release analysis exhibited a constant release over 29 days. The pDNA was completely combined with HA/CS nanoparticles and the HA/CS nanoparticles protected pDNA from degradation. Subsequently, rat synoviocytes were transfected with HA/CS/pDNA nanoparticles, and the results demonstrated that the HA/CS nanoparticles were able to improve the transfection capacity of pDNA. The cytotoxicity of the HA/CS/pDNA nanoparticles was additionally detected using a MTS assay to ensure that the HA/CS nanoparticle was a safe carrier. To additionally investigate the effects of HA/CS/pCrmA nanoparticles on synoviocytes in OA, the MMP‑3 and MMP‑13 gene expression levels were detected at the gene and protein expression levels. These results indicated that the HA/CS/pCrmA nanoparticles attenuated interleukin‑1β‑mediated inflammation in synoviocytes. It was concluded that the HA/CS/pCrmA nanoparticles may provide a novel approach to the treatment of OA.
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