4-Octyl itaconate protects chondrocytes against IL-1ß-induced oxidative stress and ferroptosis by inhibiting GPX4 methylation in osteoarthritis.

The role of oxidative stress and ferroptosis in osteoarthritis (OA) pathogenesis is increasingly recognized. Notably, 4-octyl Itaconate (OI) has been documented to counteract oxidative stress and inflammatory responses, highlighting its therapeutic potential in OA. This study explored the effects of OI on GPX4 methylation, oxidative stress, and ferroptosis in chondrocytes affected by OA. Our results demonstrated that OI mitigated IL-1ß-induced chondrocyte degeneration in a dose-dependent manner. It also suppressed reactive oxygen species (ROS) production and sustained GPX4 expression, thereby attenuating the degenerative impact of IL-1ß and Erastin on chondrocytes by curtailing ferroptosis. Moreover, we observed that blocking GPX4 methylation could alleviate IL-1ß-induced degeneration, oxidative stress, and ferroptosis in chondrocytes. The regulatory mechanism of OI on GPX4 expression in chondrocytes involved the inhibition of GPX4 methylation. In a mouse model of OA, OI's protective effects against OA were comparable to those of Ferrostatin-1. Thus, OI reduced chondrocyte degeneration, oxidative stress, and ferroptosis by inhibiting GPX4 methylation, offering a novel mechanistic insight into its therapeutic application in OA.

[Experimental study on repair of articular cartilage defects with homograft of marrow mesenchymal stem cells seeded onto poly-L-lactic acid/gelatin].

OBJECTIVE: To investigate the effect of homograft of marrow mesenchymal stem cells (MSCs) seeded onto poly-L-lactic acid (PLLA)/gelatin on repair of articular cartilage defects. METHODS: The MSCs derived from 36 Qingzilan rabbits, aging 4 to 6 months and weighed 2.5-3.5 kg were cultured in vitro and seeded onto PLLA/gelatin. The MSCs/PLLA/gelatin composite was cultured and transplanted into full thickness defects on intercondylar fossa. Thirty-six healthy Qingzilan rabbits were made models of cartilage defects in the intercondylar fossa. These rabbits were divided into 3 groups according to the repair materials with 12 in each group: group A, MSCs and PLLA/gelatin complex (MSCs/PLLA/gelatin); group B, only PLLA/gelatin; and group C, nothing. At 4, 8 and 12 weeks after operation, the gross, histological and immunohistochemical observations were made, and grading scales were evaluated. RESULTS: At 12 weeks after transplantation, defect was repaired and the structures of the cartilage surface and normal cartilage was in integrity. The defects in group A were repaired by the hyline-like tissue and defects in groups B and C were repaired by the fibrous tissues. Immunohistochemical staining showed that cells in the zones of repaired tissues were larger in size, arranged columnedly, riched in collagen II matrix and integrated satisfactorily with native adjacent cartilages and subchondral bones in group A at 12 weeks postoperatively. In gross score, group A (2.75 +/- 0.89) was significantly better than group B (4.88 +/- 1.25) and group C (7.38 +/- 1.18) 12 weeks after operation, showing significant differences (P < 0.05); in histological score, group A (3.88 +/- 1.36) was better than group B (8.38 +/- 1.06) and group C (13.13 +/- 1.96), and group B was better than group C, showing significant differences (P < 0.05). CONCLUSION: Transplantation of mesenchymal stem cells seeded onto PLLA/gelatin is a promising way for the treatment of cartliage defects.