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Increased Hif-2Α Activity In The Nucleus Pulposus Causes Intervertebral Disc Degeneration In The Aging Mouse Spine, Shira N Johnston, Maria Tsingas, Rahatul Ain, Ruteja A Barve, Makarand Risbud

Department of Orthopaedic Surgery Faculty Papers

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 …