Low oxygen response protein controls cartilage and collagen production through NOTCH1 signaling in spinal disc cells during disc degeneration

NOTCH1 expression is decreased in nucleus pulposus cells from degenerated human intervertebral discs.

• Overexpression of HIF-1α increases NOTCH1 expression, the NOTCH1 ligand JAGGED1, and its target gene HES1.
• HIF-1α overexpression also upregulates collagen Π and aggrecan in human nucleus pulposus cells.
• Inhibition of NOTCH1 with DAPT significantly suppresses changes in collagen Π and aggrecan expression.
• The HIF-1α-NOTCH1 pathway influences extracellular matrix turnover by altering matrix metalloproteinases and tissue inhibitors.
• Activating NOTCH1 via JAGGED1 in degenerated nucleus pulposus cells restores collagen Π and aggrecan expression.

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