The molecular mechanisms driving chondrocyte senescence in osteoarthritis (OA) remain largely uncertain. Korean researchers at Sungkyunkwan university have now identified the role of ZMIZ1-GATA4 signaling in age-related OA progression and propose K-7174 as a potential therapeuatic compound. This study was published in the journal Advanced Science in March.

Chondrocyte senescence accelerates OA by promoting cartilage breakdown and SASP expresssion. The researchers found that ZMIZ1, a transcriptional co-activator, works with GATA4, a key senescence-associated transcription factor. Activation of this pathway worsens OA severity and cartilage senescence.

To counteract this, they tested K-7174, a inhibitor of GATA4. Their findings showed that K-7174 suppresses ZMIZ1-GATA4 driven senescence, reducing SASPs and preserving cartilage integrity.

“This is the first study linking ZMIZ1-GATA4 axis to chondrocyte senescence,” the researchers noted. “K-7174 holds promise as a novel therapy to slow aging-related OA progression.”

By identifying a key molecular driver of OA and a potential treatment, this research paves the way for new therapeutic approaches to improve joint health.

The ZMIZ1-GATA4 interaction accelerates aging-related osteoarthritis, while K-7174 inhibits this mechanism.

[Reference]  Nam J. et al., (2025) “Blockade of ZMIZ1-GATA4 Axis Regulation Restores Youthfulness to Aged cartilage.” Advanced Science

[Main Author] Jiho Nam (Department of Biological science of Sungkyunkwan university), Siyoung Yang (Department of Biological science of Sungkyunkwan university)

* Contact email : Professor Siyoung Yang (yangsy@skku.edu)