Prolyl Hydroxylase 3 (PHD3) Modulates Catabolic Effects of Tumor Necrosis Factor-α (TNF-α) on Cells of the Nucleus Pulposus through Co-activation of Nuclear Factor κB (NF-κB)/p65 Signaling

Abstract

Background:The regulation of PHD expression and function under inflammatory conditions in the nucleus pulposus is unknown. Results: Expression of PHD3 is regulated by TNF-␣ and IL-1␤. PHD3 controls TNF-␣ activity by modulating NF-B signaling. Conclusion: PHD3 promotes the catabolic effects of TNF-␣ on nucleus pulposus cells. Significance: PHD3 may play an important role in pathogenesis of disc disease.

CCN2 Suppresses Catabolic Effects of Interleukin-1β through α5β1 and αVβ3 Integrins in Nucleus Pulposus Cells

“…Previous studies by our group and others have implicated several IL-1␤-induced genes in the progression of intervertebral disc degeneration, including matrix degrading enzymes, MMP-3, and ADAMTS-5, as well as PHD3 and syndecan 4 (3,34,35). Although CCN2 treatment alone had little effect on basal expression of these catabolic genes, when combined with IL-1␤, it significantly suppressed the inductive effect of IL-1␤.…”

Prolyl-4-hydroxylase Domain Protein 2 Controls NF-κB/p65 Transactivation and Enhances the Catabolic Effects of Inflammatory Cytokines on Cells of the Nucleus Pulposus

“…5D). Our previous studies have shown that MEFs mimic many aspects of p65 transcriptional response in NP cells (29,31). We therefore used MEFs derived from p65…”

FIH-1-Mint3 Axis Does Not Control HIF-1α Transcriptional Activity in Nucleus Pulposus Cells

“…Moreover, FIH-1 has also recently been reported to interact with and inhibit the proapoptotic protein Bax, independent of its hydroxylase activity (45). In light of our recent finding of PHD3 activating p65 signaling in NP cells independent of proline hydroxylation (46), it is important to also consider the potential role of FIH-1 independent of asparagine hydroxylation in NP physiology.…”