Irisin Ameliorates Intervertebral Disc Degeneration by Activating LATS/YAP/CTGF Signaling.

Area of Science:

• Biochemistry
• Cell Biology
• Regenerative Medicine

Background:

• Intervertebral disc degeneration (IDD) is linked to imbalanced extracellular matrix (ECM) metabolism in nucleus pulposus cells (NPCs).
• Irisin, a myokine from fibronectin type III domain-containing 5 (FNDC5), regulates ECM metabolism, but its role in IDD is unclear.

Purpose of the Study:

• To investigate the protective effects and molecular mechanisms of irisin in intervertebral disc degeneration (IDD).
• To explore irisin's impact on nucleus pulposus cells (NPCs) and ECM metabolism.

Main Methods:

• Analysis of FNDC5, COL2A1, ACAN, and ADAMTS4 expression in degenerative NP tissues.
• In vivo study using a rat IDD model with irisin treatment.
• In vitro study using TNF-α-stimulated NPCs treated with irisin.
• RNA sequencing to identify signaling pathways affected by irisin.
• Investigation of the Hippo signaling pathway (LATS, YAP) and CTGF involvement.

Main Results:

• Degenerative NP tissues showed decreased FNDC5 and anabolic markers (COL2A1, ACAN) with increased catabolic markers (ADAMTS4).
• Irisin treatment slowed IDD progression in rats and reversed ECM metabolic disorder in stimulated NPCs.
• Irisin modulated the Hippo pathway, downregulating LATS/YAP phosphorylation and upregulating CTGF.
• CTGF knockdown partially abolished irisin's protective effects on NPC ECM metabolism.

Conclusions:

• Irisin treatment promotes ECM anabolism and inhibits catabolism in NPCs, delaying IDD progression.
• The protective effects of irisin involve the LATS/YAP/CTGF signaling pathway.
• Irisin represents a potential therapeutic target for treating intervertebral disc degeneration.