Cinnamaldehyde Inhibits Leptin-Induced MMP-1 by Modulating Leptin Receptor/STAT3 and Blocking RhoA/NF-κB Pathways in Human Intervertebral Disc Stem Cells

TL;DR

Cinnamaldehyde may help prevent disc degeneration in obese individuals by reducing MMP-1 expression through specific signaling pathways.

Contribution

This study identifies cinnamaldehyde as a novel natural compound that inhibits leptin-induced MMP-1 via modulation of key signaling pathways.

Findings

Leptin induces MMP-1 via JAK2/STAT3, JAK2/RhoA/STAT3, and RhoA/ERK1/2/NF-κB pathways.

Cinnamaldehyde reduces MMP-1 by inhibiting leptin receptor and STAT3 phosphorylation.

Cinnamaldehyde blocks RhoA and NF-κB activation without affecting JAK2 or ERK1/2.

Abstract

Obesity is a recognized risk factor for intervertebral disc (IVD) degeneration, a condition characterized by the progressive loss of extracellular matrix components in the nucleus pulposus. Elevated circulating leptin levels in obese individuals contribute to this degeneration by upregulating matrix metalloproteinase-1 (MMP-1) expression. Targeting MMP-1 expression with low-toxicity natural compounds may provide a promising strategy to prevent or mitigate IVD degeneration. In this study, we examined the effects of cinnamaldehyde (CA), a natural compound derived from Cinnamomum osmophloeum Kaneh, on leptin-induced MMP-1 expression in human IVD cartilage endplate-derived stem cells (SV40 cell line). Our results showed that leptin induced MMP-1 expression via activation of leptin receptor-mediated JAK2/STAT3, JAK2/RhoA/STAT3, and RhoA/ERK1/2/NF-κB signaling pathways. CA significantly reduced MMP-1 expression by inhibiting phosphorylation of the leptin receptor and STAT3 and blocking RhoA and NF-κB activation, without affecting JAK2 and ERK1/2 phosphorylation. These findings suggest that CA suppresses leptin-induced MMP-1 expression by modulating specific signaling pathways, highlighting its potential as a therapeutic agent for IVD degeneration associated with obesity.

Figures