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Exploring the Regulators of Keratinization: Role of BMP-2 in Oral Mucosa

Overview
Journal Cells
Publisher MDPI
Date 2024 May 24
PMID 38786031
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Abstract

The oral mucosa functions as a physico-chemical and immune barrier to external stimuli, and an adequate width of the keratinized mucosa around the teeth or implants is crucial to maintaining them in a healthy and stable condition. In this study, for the first time, bulk RNA-seq analysis was performed to explore the gene expression of laser microdissected epithelium and lamina propria from mice, aiming to investigate the differences between keratinized and non-keratinized oral mucosa. Based on the differentially expressed genes (DEGs) and Gene Ontology (GO) Enrichment Analysis, bone morphogenetic protein 2 (BMP-2) was identified to be a potential regulator of oral mucosal keratinization. Monoculture and epithelial-mesenchymal cell co-culture models in the air-liquid interface (ALI) indicated that BMP-2 has direct and positive effects on epithelial keratinization and proliferation. We further performed bulk RNA-seq of the ALI monoculture stimulated with BMP-2 in an attempt to identify the downstream factors promoting epithelial keratinization and proliferation. Analysis of the DEGs identified, among others, , , , , , , and as key factors. In summary, these results revealed the involvement of a well-known growth factor responsible for bone development, BMP-2, in the mechanism of oral mucosal keratinization and proliferation, and pointed out the possible downstream genes involved in this mechanism.

References
1.
Gosselet F, Magnaldo T, Culerrier R, Sarasin A, Ehrhart J . BMP2 and BMP6 control p57(Kip2) expression and cell growth arrest/terminal differentiation in normal primary human epidermal keratinocytes. Cell Signal. 2006; 19(4):731-9. DOI: 10.1016/j.cellsig.2006.09.006. View

2.
Caddy J, Luoma L, Berry F . FOXC1 negatively regulates BMP-SMAD activity and Id1 expression during osteoblast differentiation. J Cell Biochem. 2020; 121(5-6):3266-3277. DOI: 10.1002/jcb.29595. View

3.
Lowery J, Rosen V . The BMP Pathway and Its Inhibitors in the Skeleton. Physiol Rev. 2018; 98(4):2431-2452. DOI: 10.1152/physrev.00028.2017. View

4.
Hamajima Y, Komori M, Preciado D, Choo D, Moribe K, Murakami S . The role of inhibitor of DNA-binding (Id1) in hyperproliferation of keratinocytes: the pathological basis for middle ear cholesteatoma from chronic otitis media. Cell Prolif. 2010; 43(5):457-63. PMC: 2950310. DOI: 10.1111/j.1365-2184.2010.00695.x. View

5.
Bosanquet D, Harding K, Ruge F, Sanders A, Jiang W . Expression of IL-24 and IL-24 receptors in human wound tissues and the biological implications of IL-24 on keratinocytes. Wound Repair Regen. 2012; 20(6):896-903. DOI: 10.1111/j.1524-475X.2012.00840.x. View