A possibility to regulate joint aging, a type of physical aging disease, has been suggested.
The National Research Foundation of Korea announced on the 28th that a joint research team consisting of Professor Yang Si-young and graduate student Nam Ji-ho from the Department of Life Sciences at Sungkyunkwan University and Professor Yoon Sung-il from Chung-Ang University identified the activation mechanism of the protein (ZMIZ1) that promotes osteoarthritis and discovered a small molecule compound (a compound under 1000 Da) that can regulate the activity of ZMIZ1.
(From left) Professor Yang Si-young of the Department of Life Sciences at Sungkyunkwan University, graduate student Nam Ji-ho, and Professor Yoon Sung-il of Chung-Ang University. Provided by the National Research Foundation of Korea
Osteoarthritis is a representative physical aging disease that begins with the aging of joint cartilage cells. According to statistics from Statistics Korea, 19.2% of elderly people aged 65 or older in Korea suffer from osteoarthritis.
This disease requires surgical treatment in severe cases, but surgical procedures have limitations in suppressing or recovering joint damage, increasing the burden on elderly patients. Therefore, the need for developing osteoarthritis treatments is growing, but basic research on cartilage cell aging has been insufficient until now.
Considering this situation, the joint research team used gene sequencing datasets (data containing DNA or RNA sequence information of organisms) within cartilage tissue to identify transcriptional regulators (proteins that regulate gene expression) that increase activity under aging conditions. They discovered that the expression of the ZMIZ1 protein increases in cartilage tissue where cartilage cell aging has progressed.
Additionally, during the research process, they confirmed that ZMIZ1 binds with GATA4 (a transcriptional regulatory protein belonging to the GATA transcription factor family) to accelerate the onset of arthritis. Using an AI-based screening platform, they also revealed that the small molecule compound K-7174 inhibits the binding of ZMIZ1-GATA4.
The joint research team conducted experiments administering K-7174 orally or via intra-articular injection to animals suffering from osteoarthritis. As a result, they confirmed the process of cartilage damage and aging joints recovering to healthy, younger joints.
This study is significant in that it elucidated the ZMIZ1-GATA4 mechanism that accelerates osteoarthritis and confirmed the effect of a drug that inhibits this mechanism, suggesting the possibility of disease recovery.
Professor Yang Si-young said, “By discovering a new factor that plays an important role in suppressing aging cartilage cells, the joint research team is expected to play a crucial role in developing more effective treatments for osteoarthritis.”
Meanwhile, this research was conducted with support from the Bio-Medical Technology Development Project and Mid-Career Research Program promoted by the Ministry of Science and ICT and the National Research Foundation of Korea, as well as the Pan-Government Regenerative Medical Technology Development Project jointly promoted by the Ministry of Science and ICT and the Ministry of Health and Welfare. The research results were published on the 5th in the international journal Advanced Science.
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