Strontium Changes Lipid Profile, Release, and Function of Matrix Vesicles Produced by Mineralization-Competent Cells

Area of Science:

• Biochemistry
• Cell Biology
• Biomaterials Science

Background:

• Extracellular matrix (ECM) mineralization is crucial for bone health, initiated by matrix vesicles (MVs).
• Osteogenic inducers like strontium ranelate (SR) are vital for treating bone pathologies.
• The role of strontium ions (Sr²⁺) in MV-mediated mineralization remains underexplored.

Purpose of the Study:

• To investigate how Sr²⁺ influences MV release and function in mineralization.
• To determine the effect of Sr²⁺ on osteogenic signaling pathways (Erk1/2, CREB).
• To analyze Sr²⁺-induced changes in MV lipid profiles and their impact on bone formation.

Main Methods:

• Cell viability assessed via MTT assay; mineralization tracked by Alizarin Red and Von Kossa staining.
• Western blotting for ERK and CREB phosphorylation; qPCR for osteogenic gene expression.
• MV characterization using NTA, DLS, zeta potential, turbidimetry, FTIR, AFM, and TEM; lipidomics for lipid profile analysis.

Main Results:

• Sr²⁺ activates Erk1/2 and CREB pathways, dose-dependently increasing ECM mineralization.
• Altered MV viscoelastic properties and lipid composition (enriched ceramide and sphingomyelin) observed in Sr²⁺-stimulated cells.
• Sr²⁺ influences MV biogenesis and function, crucial for bone development.

Conclusions:

• Sr²⁺ modulates the initiation of mineralization by altering MV release and lipid composition.
• The Erk1/2 and CREB signaling pathways are key mediators of Sr²⁺'s effects on mineralization.
• Findings provide insights into SR's therapeutic potential for bone disorders.