# Runx1 overexpression induces early onset of intervertebral disc degeneration

## TL;DR

Overexpression of Runx1 in mice leads to early disc degeneration, suggesting a new role for Runx1 in spinal disc health.

## Contribution

This study reveals a novel role for Runx1 in initiating intervertebral disc degeneration through NP-specific overexpression.

## Key findings

- Runx1 overexpression in the nucleus pulposus causes early onset disc degeneration in mice.
- Runx1 overexpression leads to extracellular matrix remodeling and increased senescence markers.
- Degeneration severity correlates with Runx1 expression levels in transgenic mice.

## Abstract

Intervertebral disc degeneration (IDD) is closely associated with aging. Although the Runt-related transcription factor 1 (RUNX1) is well known for its role in skeletal development and other musculoskeletal related diseases such as osteoarthritis, its involvement in IDD pathogenesis remains elusive. In this study, we examined the function of Runx1 specifically in the nucleus pulposus (NP) in vivo. To achieve NP-specific postnatal overexpression of Runx1, we crossed Krt19CreERT mice with Rosa26-Runx1 transgenic mice previously generated in our laboratory. Mice with NP specific Runx1 overexpression displayed early onset and progressive disc degeneration beginning at 5 months of age. This was characterized by a phenotypic shift from notochordal cells to hypertrophic chondrocyte-like cells, accompanied by extracellular matrix remodeling, including reduced expression of aggrecan and type II collagen as well as increased type X collagen. In addition, NP cells from these transgenic mice showed increased expression of senescence markers P16 and P21 without significant changes in apoptosis levels. Notably, the severity of degeneration correlated with the number of tamoxifen injections, suggesting a direct association between the level of Runx1 expression and IVD degeneration. Early histological signs of degeneration in Runx1 overexpression mice highlighted its potential role as a key IDD initiator. Taken together, these findings reveal a novel role of Runx1 in maintaining disc health and regulating age-related degenerative processes.