MMP-12-Induced Pro-osteogenic Responses in Human Aortic Valve Interstitial Cells

Area of Science:

• Cardiovascular Biology
• Molecular Pathology
• Biomaterials Science

Background:

• Calcific aortic valve disease (CAVD) is a progressive valvular disorder associated with aging.
• Matrix metalloproteinase 12 (MMP-12) is implicated in atherosclerosis and vascular stiffening.
• Elevated MMP-12 levels are observed in calcified aortic valves.

Purpose of the Study:

• To investigate the role of MMP-12 in inducing pro-osteogenic responses in human aortic valve interstitial cells (AVICs).
• To elucidate the signaling pathways involved in MMP-12-mediated osteogenesis in CAVD.

Main Methods:

• Human AVICs were isolated from normal and calcified aortic valves.
• Cells were treated with MMP-12, and key osteogenic markers (RUNX-2, BMP-2, ALP) and signaling molecules were analyzed.
• Inhibitors of MMP-12, p38 MAPK, and LRP-6 were used to assess pathway involvement.

Main Results:

• Calcified aortic valves showed significantly higher MMP-12 expression compared to normal valves.
• MMP-12 treatment increased RUNX-2, BMP-2, ALP expression, and calcium deposition in AVICs.
• MMP-12-induced osteogenesis involved p38 MAPK and LRP-6/β-catenin signaling pathways.

Conclusions:

• MMP-12 promotes osteogenic responses in AVICs via p38 MAPK-mediated LRP-6 and β-catenin signaling.
• MMP-12 plays a critical role in the pathogenesis of CAVD.
• Targeting MMP-12 presents a potential therapeutic strategy for CAVD.