Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model
Background/Aims: Interleukin (IL)-1β plays an essential role in the pathophysiology of osteoarthritis (OA). Cytokine response modifier A (CrmA) can prevent the generation of active IL-1β. This study aimed to explore the chondroprotective effects of hyaluronic acid-chitosan nanoparticles containing p...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2018-06-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/490217 |
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| author | Pang-hu Zhou Bo Qiu Rong-hui Deng Hua-jie Li Xiong-feng Xu Xi-fu Shang |
| author_facet | Pang-hu Zhou Bo Qiu Rong-hui Deng Hua-jie Li Xiong-feng Xu Xi-fu Shang |
| author_sort | Pang-hu Zhou |
| collection | DOAJ |
| description | Background/Aims: Interleukin (IL)-1β plays an essential role in the pathophysiology of osteoarthritis (OA). Cytokine response modifier A (CrmA) can prevent the generation of active IL-1β. This study aimed to explore the chondroprotective effects of hyaluronic acid-chitosan nanoparticles containing plasmid DNA encoding CrmA (HA/CS-CrmA) in a rat OA model. Methods: HA/CS-CrmA nanoparticles were synthesized through the complex coacervation of cationic polymers. The characteristics, toxicity, and transfection of the nanoparticles were investigated. Furthermore, the potential effects of HA/CS-CrmA nanoparticles were evaluated via a rat anterior cruciate ligament transection (ACLT) model of OA. Cartilage damage and synovial inflammation were assessed by safranin O/fast green and hematoxylin and eosin staining. Type II collagen in cartilage was measured by immunohistochemistry, and the expression levels of IL-1β, matrix metalloproteinase (MMP)-3, and MMP-13 in synovial tissue were detected by western blot. Results: The HA/CS-CrmA nanoparticles, which effectively entrapped plasmid DNA, showed an adequate size (100-300 nm) and a regular spherical shape. The nanoparticles safely transfected synoviocytes and released plasmid DNA in a sustained manner over 3 weeks. Additionally, HA/CS-CrmA nanoparticles significantly inhibited cartilage damage, synovial inflammation, and the loss of type II collagen induced by ACLT. The expression levels of IL-1β, MMP-3, and MMP-13 in synovial tissue were dramatically down-regulated by HA/CS-CrmA nanoparticles. Conclusions: These results suggested that HA/CS-CrmA nanoparticles could attenuate cartilage destruction and protect against early OA by inhibiting synovial inflammation via inhibition of IL-1β generation. |
| first_indexed | 2024-04-13T06:14:34Z |
| format | Article |
| id | doaj.art-85d15150ee424eb4bc410f9edb572339 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-13T06:14:34Z |
| publishDate | 2018-06-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-85d15150ee424eb4bc410f9edb5723392022-12-22T02:58:53ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-06-014731207121610.1159/000490217490217Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis ModelPang-hu ZhouBo QiuRong-hui DengHua-jie LiXiong-feng XuXi-fu ShangBackground/Aims: Interleukin (IL)-1β plays an essential role in the pathophysiology of osteoarthritis (OA). Cytokine response modifier A (CrmA) can prevent the generation of active IL-1β. This study aimed to explore the chondroprotective effects of hyaluronic acid-chitosan nanoparticles containing plasmid DNA encoding CrmA (HA/CS-CrmA) in a rat OA model. Methods: HA/CS-CrmA nanoparticles were synthesized through the complex coacervation of cationic polymers. The characteristics, toxicity, and transfection of the nanoparticles were investigated. Furthermore, the potential effects of HA/CS-CrmA nanoparticles were evaluated via a rat anterior cruciate ligament transection (ACLT) model of OA. Cartilage damage and synovial inflammation were assessed by safranin O/fast green and hematoxylin and eosin staining. Type II collagen in cartilage was measured by immunohistochemistry, and the expression levels of IL-1β, matrix metalloproteinase (MMP)-3, and MMP-13 in synovial tissue were detected by western blot. Results: The HA/CS-CrmA nanoparticles, which effectively entrapped plasmid DNA, showed an adequate size (100-300 nm) and a regular spherical shape. The nanoparticles safely transfected synoviocytes and released plasmid DNA in a sustained manner over 3 weeks. Additionally, HA/CS-CrmA nanoparticles significantly inhibited cartilage damage, synovial inflammation, and the loss of type II collagen induced by ACLT. The expression levels of IL-1β, MMP-3, and MMP-13 in synovial tissue were dramatically down-regulated by HA/CS-CrmA nanoparticles. Conclusions: These results suggested that HA/CS-CrmA nanoparticles could attenuate cartilage destruction and protect against early OA by inhibiting synovial inflammation via inhibition of IL-1β generation.https://www.karger.com/Article/FullText/490217Cytokine response modifer AHyaluronic acidChitosanNanoparticlesGene deliveryOsteoarthritis |
| spellingShingle | Pang-hu Zhou Bo Qiu Rong-hui Deng Hua-jie Li Xiong-feng Xu Xi-fu Shang Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model Cellular Physiology and Biochemistry Cytokine response modifer A Hyaluronic acid Chitosan Nanoparticles Gene delivery Osteoarthritis |
| title | Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model |
| title_full | Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model |
| title_fullStr | Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model |
| title_full_unstemmed | Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model |
| title_short | Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model |
| title_sort | chondroprotective effects of hyaluronic acid chitosan nanoparticles containing plasmid dna encoding cytokine response modifier a in a rat knee osteoarthritis model |
| topic | Cytokine response modifer A Hyaluronic acid Chitosan Nanoparticles Gene delivery Osteoarthritis |
| url | https://www.karger.com/Article/FullText/490217 |
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