Runx1 overexpression causes early intervertebral disc degeneration

A new research article was published in Volume 17, Issue 9 dated September 8, 2025, titled “Runx1 Overexpression Induces Early Onset intervertebral disc degeneration.”

In this study, led by first author Takanori Fukunaga of Emory University School of Medicine and corresponding author Hicham Drissi of Emory and the Atlanta VA Medical Center, researchers found that the Runx1 gene, when overactive in intervertebral disc cells, can accelerate age-related disc degeneration intervertebral discs. The findings offer new insight into the genetic factors responsible for disc aging and suggest possible directions for treating chronic back pain.

Intervertebral discs cushion the spine and support movement. Their deterioration is the main cause of lower back pain, especially as we age. At the center of each disc is the nucleus pulposus (NP), a gel-like core containing proteins such as collagen and aggrecan that help retain water and maintain structure. As we age, NP cells often lose their function, contributing to disc damage.

Using a genetically modified mouse model, the researchers activated Runx1 specifically in NP cells. These mice showed signs of disc degeneration at five months of age, much earlier than normal. Overexpression of Runx1 led to the loss of healthy NP cells, an increase in abnormal cell types, and damage to disc structure. Levels of essential proteins such as aggrecan and type II collagen decreased, while type X collagen levels increased, signaling unhealthy changes in tissues.

The key finding was that excessive Runx1 activity did not directly kill cells. Instead, it caused premature aging of cells, known as senescence. Senescent cells lose their ability to repair tissues, creating an environment that accelerates degeneration. Senescence markers were significantly elevated in the affected discs.

The researchers also observed a dose-dependent response. The more Runx1 was activated, the more severe the degeneration. This suggests that targeting Runx1 may be a promising strategy to prevent or slow disk aging.

Overall, this study highlights the genetic and cellular processes that contribute to intervertebral disc degeneration, a leading cause of disability. By identifying Runx1 as a potential driver of early intervertebral disc aging, the study opens new avenues for intervention and treatment of degenerative spine disorders.