Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model

• Published in: Cellular physiology and biochemistry Vol. 47; no. 3; pp. 1207 - 1216
• Main Authors: Zhou, Pang-hu, Qiu, Bo, Deng, Rong-hui, Li, Hua-jie, Xu, Xiong-feng, Shang, Xi-fu
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland S. Karger AG 01.01.2018; Cell Physiol Biochem Press GmbH & Co KG
• Subjects: Animals; Apoptosis; Arthritis; Biomedical materials; Chitosan; Chitosan - pharmacology; Cytokine response modifer A; Cytokines; Cytokines - metabolism; Deoxyribonucleic acid; Disease Models, Animal; DNA; Enzymes; Fibroblasts; Gene delivery; Gene therapy; Growth factors; Hyaluronic acid; Hyaluronic Acid - pharmacology; Inflammation; Knee; Laboratory animals; Molecular weight; Morphology; Nanoparticles; Original Paper; Osteoarthritis; Osteoarthritis, Knee - metabolism; Osteoarthritis, Knee - pathology; Osteoarthritis, Knee - therapy; Pathogenesis; Plasmids - genetics; Plasmids - pharmacology; Rats; Serpins - biosynthesis; Serpins - genetics; Tumor necrosis factor-TNF; Vectors (Biology); Viral Proteins - biosynthesis; Viral Proteins - genetics; United States > US; Nanoparticles; Gene delivery; Chitosan; Hyaluronic acid; Osteoarthritis; Cytokine response modifer A
• ISSN: 1015-8987; 1421-9778
• DOI: 10.1159/000490217

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.