Runx1 overexpression triggers early intervertebral disc degeneration

A new research article was published in Volume 17, Issue 9 of Aging-US on September 8, 2025, titled “Runx1 overexpression induces early onset of 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 spinal disc cells, can accelerate age-related degeneration of intervertebral discs. The findings offer new insights into the genetic factors that drive disc aging and suggest possible directions for the treatment of chronic back pain.

Intervertebral discs cushion the spine and support movement. Its deterioration is one of the main causes of low back pain, especially with aging. At the center of each disc is the nucleus pulposus (NP), a gel-like core that contains proteins such as collagen and aggrecan, which help retain water and maintain structure. As people age, NP cells often lose their function, contributing to disc degradation.

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

“To achieve NP-specific postnatal Runx1 overexpression, we crossed Krt19CreERT mice with Rosa26-Runx1 transgenic mice previously generated in our laboratory.”

A key finding was that overactivity of Runx1 did not kill cells directly. Instead, it caused premature cellular aging, known as senescence. Senescent cells lose the ability to repair tissues, creating an environment that accelerates degeneration. Markers of senescence were significantly elevated in 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 disc 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 possible driver of early disc aging, the research opens new opportunities for intervention and treatment of degenerative spinal conditions.