Increased HIF-2α activity in the nucleus pulposus causes intervertebral disc degeneration in the aging mouse spine.

ABSTRACT: Hypoxia-inducible factors (HIFs) are essential to the homeostasis of hypoxic tissues. Although HIF-2α, is expressed in nucleus pulposus (NP) cells, consequences of elevated HIF-2 activity on disc health remains unknown. We expressed HIF-2α with proline to alanine substitutions (P405A; P531A) in the Oxygen-dependent degradation domain (HIF-2αdPA) in the NP tissue using an inducible, nucleus pulposus-specific K19^CreERT allele to study HIF-2α function in the adult intervertebral disc. Expression of HIF-2α in NP impacted disc morphology, as evident from small but significantly higher scores of degeneration in NP of 24-month-old K19^CreERT; HIF-2α^dPA (K19-dPA) mice. Noteworthy, comparisons of grades within each genotype between 14 months and 24 months indicated t

SUBMITTER: Johnston SN 

PROVIDER: S-EPMC10950937 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature