Attenuation of osteoarthritis progression in mice following intra‐articular administration of simvastatin‐conjugated gelatin hydrogel

Abstract

Simvastatin is clinically used for the treatment of hypercholesterolaemia. This study investigated the effects of the intra-articular administration of a simvastatin-conjugated gelatin hydrogel on osteoarthritis (OA) progression in a murine model. The medial meniscus of the knee joint was de-stabilized to induce OA in 10-week-old mice. Mice were then intra-articularly injected with dimethyl sulfoxide (control), drug-free gelatin hydrogel, simvastatin, or simvastatin-conjugated gelatin hydrogel. At 8 weeks postsurgery, OA progression was significantly attenuated in the simvastatin-conjugated gelatin hydrogel-treated mice compared with the other three groups. Attenuation of OA in mice treated with simvastatin-conjugated gelatin hydrogel was associated with decreased expression of cartilage-degrading enzymes and interleukin (IL)-1β and increased expression of type II collagen and an autophagic marker, LC3, in the articular cartilage. The effects of simvastatin on gene expression and autophagy in the mouse primary chondrocytes were also examined in the presence or absence of IL-1β. Treatment with simvastatin down-regulated Mmp-13 and Il-1β and up-regulated Col2a1 and autophagic activity. Our findings suggest that the intraarticular administration of simvastatin-conjugated gelatin hydrogel could be used as a new potential therapy for OA.

KLF2 Protects against Osteoarthritis by Repressing Oxidative Response through Activation of Nrf2/ARE Signaling In Vitro and In Vivo

“…Previously, studies have reported that simvastatin significantly inhibits the IL-1 β -induced production of matrix-degrading enzymes in vitro and protects against the development of cartilage degeneration in OA model mice [46, 47]. It has also been reported that simvastatin triggers the nuclear translocation of Nrf2 in the rat liver [48].…”

Gelatin hydrogels with eicosapentaenoic acid can prevent osteoarthritis progression in vivo in a mouse model

“…Matsuzaki et al 18 reported that gelatin hydrogels incorporating rapamycin gradually release rapamycin within approximately 2 days in vitro, but they release rapamycin for approximately 10 weeks in vivo 18 . Furthermore, gelatin hydrogels incorporating simvastatin have been reported to exhibit sustained release for at least 3 weeks in vitro and 4 weeks in vivo 19,34 . The present study used EPA‐incorporating hydrogel formulation solubilized in water into gelatin micelles.…”

A novel topical treatment for bone metastases using a gelatin hydrogel incorporating cisplatin as a sustained release system

“…Thus, it has great potential for use in medical, pharmaceutical, and cosmetic applications. Because a gelatin hydrogel has the advantages of biological safety and spatial stability, it has been widely used in many clinical studies as a drug delivery system 14,17,21–26 . However, the conventional procedure to prepare GM‐CDDP uses glutaraldehyde or organic solvents that are harmful to the human body.…”

“…Because a gelatin hydrogel has the advantages of biological safety and spatial stability, it has been widely used in many clinical studies as a drug delivery system. 14,17,[21][22][23][24][25][26] However, the conventional procedure to prepare GM-CDDP uses glutaraldehyde or organic solvents that are harmful to the human body. Thus, we developed a new procedure using a F I G U R E 4 (A) Representative images of each group in 3D-μCT at 2 weeks after treatment.…”