Chondroprotective Effects of Hyaluronic Acid-Chitosan Nanoparticles Containing Plasmid DNA Encoding Cytokine Response Modifier A in a Rat Knee Osteoarthritis Model.
Cell Physiol Biochem
; 47(3): 1207-1216, 2018.
Article
en En
| MEDLINE
| ID: mdl-29913441
ABSTRACT
BACKGROUND/AIMS:
Interleukin (IL)-1ß plays an essential role in the pathophysiology of osteoarthritis (OA). Cytokine response modifier A (CrmA) can prevent the generation of active IL-1ß. 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-1ß, 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-1ß, 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-1ß generation.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Plásmidos
/
Proteínas Virales
/
Serpinas
/
Osteoartritis de la Rodilla
/
Quitosano
/
Nanopartículas
/
Ácido Hialurónico
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Physiol Biochem
Asunto de la revista:
BIOQUIMICA
/
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY