Rejuvenate the knee joint! Liangzhu Laboratory discovered the aging gene of articular cartilage

As the saying goes, "When a tree grows old, its roots wither first; when a person grows old, his legs weaken first." Restoring the legs to a youthful state has always been a dream of people, and thanks to the efforts of scientists, it is gradually becoming a reality.

Recently, Ouyang Hongwei's team at Liangzhu Laboratory discovered the aging gene ADAM19 in chondrocytes and developed a new method, which provides new ideas for the treatment of osteoarthritis. The related research was published in Advanced Science.

One of the main pathological characteristics of osteoarthritis is the accumulation of senescent cells in the joints. These senescent cells not only fail to proliferate normally, but also release inflammatory factors that damage the joint environment. Although existing "senescent cell removers" can remove senescent cells, long-term use may lead to the exhaustion of stem cells and progenitor cells, affecting the regeneration ability of cartilage.

ADAM19-positive senescent chondrocytes are significantly increased in osteoarthritic joints of mice and humans

Finding a treatment method that can reverse the aging phenotype of chondrocytes and promote cartilage regeneration has become the research direction of osteoarthritis.

The researchers found that by deleting the ADAM19 gene in chondrocytes, the aging symptoms of articular cartilage can be alleviated, the cells can be rejuvenated and start working, inflammatory factors are reduced, and glycosaminoglycans, the main component of articular cartilage, are significantly increased. This is equivalent to allowing "old, weak, sick and disabled" cells to return to work, thereby helping the knee joints to "rejuvenate".

If the leg with osteoarthritis is an aging machine, then ADAM19 is the rusty key screw. If you want to revitalize the machine, removing this old screw is the key.

To this end, the research team used a gene scissors called "siRNA". In order to deliver enough gene scissors into aging cartilage cells, the researchers developed a "precision delivery system" - an aging-targeted siRNA delivery system with high load capacity, which allows siRNA to accurately reach the location of aging cells and avoid accidental damage to normal cells.

"Although it is still in the animal experiment stage, it provides a new idea for achieving 'precise repair of aging joints' in the future. Future research will further optimize the delivery system, explore its application in large animal models, and evaluate its therapeutic effects in other related diseases." Relevant researchers said.

Wang Jiasheng, a doctoral student at Zhejiang University School of Medicine, is the first author of this article, Guo Peng, a master's student at Zhejiang University School of Medicine, is the co-first author, and Professor Ouyang Hongwei from Liangzhu Laboratory and Zhejiang University School of Medicine and Researcher Hu Jiajie from Zhejiang University School of Medicine are the co-corresponding authors of this article.