Runx1 overexpression triggers early intervertebral disc degeneration

A new research paper was published in Volume 17, Issue 9 of Aging-USA on September 8, 2025, titled, “Runx1 overexpression causes 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 spinal disc cells, can accelerate the degeneration of intervertebral discs associated with with age. The findings offer new insight into the genetic factors that lead to disc aging and suggest potential directions for treating chronic back pain.

Intervertebral discs cushion the spine and support movement. Their worsening is a major cause of lower back pain, especially with aging. At the center of each disc is the nucleus pulposus (NP), a gel-like core containing 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 breakdown.

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

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

A key finding was that overactivity of Runx1 did not directly kill the cells. Instead, it caused premature cellular aging, known as senescence. Aging cells lose the ability to repair tissue, creating an environment that accelerates degeneration. Aging markers 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.

Taken together, this study highlights the genetic and cellular processes that contribute to intervertebral disc degeneration, a major cause of disability. By identifying Runx1 as a potential factor in premature disc aging, the research opens up new opportunities for intervention and treatment of degenerative conditions of the spine.