Masticatory stress promotes rete ridge elongation in oral mucosa

The deficiency of the rete ridge (RR) structure leads to feeble connection between epidermis and dermis layers in tissues engineered oral mucosa (TEOM) and impaired the clinical application of TEOM in oral surgery. As little is known about RR in oral mucosa, this study aimed to investigate the morphological characteristics and the potential influence of masticatory stress in RR elongation.

Method:

RR characteristics of type, density, length and the width in oral epithelium were analyzed in 52 patients including masticatory mucosa (Mm) and lining mucosa (Lm). Ultramicro-structure difference between Mm and Lm were observed and compared under transmission electron microscope and scanning electron microscope. Expressions of ERK1/2, Ki67 and CK19 in the epidermal basal layer were assessed by immunohistochemistry to analyze their associations with RR length. Activation of ERK1/2 by masticatory stimuli was further proved by in vitro mechanical loading assay using monolayer and three dimensional cultured primary epithelial cells isolated from oral mucosa.

Result:

Human RR contained types of simple, complex and net-like rete ridges in oral mucosa, with differed characteristics between Mm and Lm. RR length was negative correlated with ERK1/2 expression (p=0.004), and positive correlated with Ki67 and CK19 expression (both p<0.05). Mechanical stimuli could activate ERK1/2 phosphorylation and promote keratinocyte propagation. Ultramicro-structure showed different hemidesmosome type, amount, and distance in epidermal-dermal connection between Mm and Lm. 

Conclusion:

Mm has longer RR than Lm. Masticatory stress activates ERK1/2 phosphorylation and subsequent basal keratinocyte activation. Those evidences together suggest that masticatory stimuli promote RR elongation through topical basal keratinocyte proliferation and migration. Our finding may contribute to future TEOM reconstruction that with enriched RR structure.