Dual-Lineage Chondrocyte-Like Cells in the Nucleus Pulposus of Aging Intervertebral Discs Are Accelerated by Hedgehog Signaling Inactivation.

ABSTRACT: Intervertebral disc (IVD) degeneration, a major contributor to chronic low back pain, is characterized by the age-related replacement of notochord-derived nucleus pulposus cells (NPCs) with chondrocyte-like or fibrotic cells (CLCs). However, the cellular origins of CLCs and mechanisms driving their emergence remain contentious. Using genetic lineage tracing with Shh-Cre and Gli1-CreER^T2 to track notochordal and non-notochordal cells, respectively, we demonstrate that CLCs arise from dual lineages: notochordal NPCs and non-notochordal Gli1⁺ progenitors. We identified three CLC subtypes, including nested (N-CLCs), clustered (C-CLCs), and disordered (D-CLCs), with distinct morphological and/or molecular profiles. N-CLCs and C-CLCs originate from NPCs, whereas D-CLCs deri

SUBMITTER: Zhang L 

PROVIDER: S-EPMC12611273 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature