HDAC1 maintains metabolic homeostasis in nucleus pulposus cells via post-translational modification interactions with YBX1

Abstract Intervertebral disc degeneration is characterized by the metabolic dysregulation of nucleus pulposus cells, which is regulated by complex post-translational modifications, manifesting as extracellular matrix remodeling and inflammatory microenvironment formation. We demonstrated the progressive downregulation of HDAC1 during disc degeneration. HDAC1 mediates the deacetylation and ubiquitination-dependent degradation of YBX1. The downregulation of HDAC1 results in YBX1 accumulation, compromising extracellular matrix synthesis in nucleus pulposus cells while enhancing the degradation processes. Furthermore, the accumulated YBX1 stimulates chemokine expression, facilitating the development of an inflammatory microenvironment. Targeting this critical axis, we developed SU056@GelMA to deliver the YBX1 inhibitor SU056, mitigating the metabolic disruption induced by YBX1 accumulation.