Substrate stiffness controls proinflammatory responses in human gingival fibroblasts

Area of Science:

• Biomaterials Science
• Cell Biology
• Periodontology

Background:

• Gingival health is often compromised by soft gingiva, but the biological mechanisms are unclear.
• Extracellular matrix (ECM) stiffness influences fibroblast-related inflammatory disorders via cellular mechanotransduction.
• Gingival stiffness may regulate mechanotransduction-mediated inflammatory responses in gingival fibroblasts.

Purpose of the Study:

• To investigate the impact of substrate stiffness on proinflammatory responses in human gingival fibroblasts (hGFs).
• To elucidate the role of ECM stiffness in regulating gingival fibroblast behavior and inflammatory signaling.

Main Methods:

• Human gingival fibroblasts (hGFs) were cultured on type I collagen-coated polydimethylsiloxane substrates with varying stiffnesses (5 kPa soft, 25 kPa hard).
• Proinflammatory mediators (prostaglandin E2, interleukin-1β) and ECM synthesis markers were quantified.
• Expression of mechanotransduction and inflammation-related factors was analyzed.

Main Results:

• Soft substrates (5 kPa) significantly increased proinflammatory mediator expression in hGFs compared to hard substrates (25 kPa), both with and without lipopolysaccharide (LPS).
• ECM synthesis and collagen cross-linking agent expression were downregulated on soft substrates over 14 days.
• Soft substrates suppressed mechanotransduction factors and activated inflammation-related factors, while hard substrates showed opposite effects.

Conclusions:

• Soft substrate stiffness induces proinflammatory responses and inhibits ECM synthesis in hGFs by inactivating cellular mechanotransduction.
• ECM stiffness is a critical factor in maintaining gingival health.
• These findings suggest that modulating gingival tissue stiffness could be a therapeutic strategy for periodontal diseases.