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. 2023 Oct-Dec;27(4):706-714.
doi: 10.4103/jomfp.jomfp_492_22. Epub 2023 Dec 20.

Role of osteopontin in oral epithelial dysplasia, oral submucous fibrosis and oral squamous cell carcinoma

Nasir A Salati  1 , Mohit Sharma  2 , Nirmala N Rao  3 , Smitha S Shetty  4 , Raghu A Radhakrishnan  4
Affiliations

Role of osteopontin in oral epithelial dysplasia, oral submucous fibrosis and oral squamous cell carcinoma

Nasir A Salati et al. J Oral Maxillofac Pathol. 2023 Oct-Dec.

Abstract

Background: Inflammatory cells and cytokines in the chronically injured mucosa promote fibrosis in the oral submucous fibrosis (OSF) fibrotic milieu. Osteopontin (OPN) is a wound-healing mediator that upregulates the inflammatory response and is involved in the malignancy and fibrosis of multiple organ systems.

Objectives: We investigated the expression of OPN in oral potentially malignant disorders (OPMDs) and oral squamous cell carcinomas (OSCCs) to determine its role in the malignant transformation and fibrosis of oral tissues. The expression of OPN in OPMDs and OSCCs was compared and correlated, and the role of OPN as a fibrotic mediator in OSF was explained.

Study design: A total of 30 cases of normal mucosa and OPMDs (mild dysplasia, severe dysplasia, OSF and OSCCs) were studied by purposive sampling. In these groups, OPN immunoreactivity was examined and correlated with clinical findings.

Results: In mild dysplasia, OPN expression was restricted to the basal cell layer with moderate staining intensity. In severe dysplasia, it was extremely intense and extended throughout the epithelium. In the OSF, OPN expression was moderate in the perinuclear areas of the basal cell layer. The expression of OPN was very strong in OSCC. A flow diagram explaining the profibrotic role of OPN in OSF has been provided.

Conclusion: A positive role of OPN in both pathogenesis and malignant transformation of OPMDs and OSCC has been demonstrated.

Keywords: Angiotensin I; angiotensin II; angiotensinogen; mast cells; oral squamous cell carcinoma; oral submucous fibrosis; osteopontin.

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Conflict of interest statement

There are no conflicts of interest.

Figures

Figure 1
Figure 1
(a) OPN expression by muscle tissue of normal oral mucosa (positive control). (b) Expression of OPN in the basal and suprabasal layers in mild dysplasia. (c) Expression of OPN in the basal, suprabasal and upper layers in severe dysplasia. (d) Expression of OPN with moderate intensity in epithelial layers in OSF. (e) Expression of OPN in tumour islands with bright intensity in OSCC
Figure 2
Figure 2
Schematic diagram illustrating the role of OPN in inflammatory and immune cell recruitment in areas of chronic injury and playing a central role in fibrosis
Figure 3
Figure 3
(a) OPN and its positive feedback mechanisms in the pathogenesis of OSF and muscle fibrosis leading to LMO. (b) Crosstalk between OPN and profibrotic mediators and the essentiality of OPN in myofibroblast differentiation. (c) Central role of OPN in fibroblast–myofibroblast transition and TGF-β activation through stimulation of mast cell granulation
See this image and copyright information in PMC

References

    1. Rybinski B, Franco-Barraza J, Cukierman E. The wound healing, chronic fibrosis, and cancer progression triad. Physiol Genomics. 2014;46:223–44. - PMC - PubMed
    1. Sharma M, Shetty SS, Radhakrishnan R. Oral submucous fibrosis as an overhealing wound:Implications in malignant transformation. Recent Pat Anticancer Drug Discov. 2018;13:272–91. - PubMed
    1. Mori R, Shaw TJ, Martin P. Molecular mechanisms linking wound inflammation and fibrosis:Knockdown of osteopontin leads to rapid repair and reduced scarring. J Exp Med. 2008;205:43–51. - PMC - PubMed
    1. Weber CE, Li NY, Wai PY, Kuo PC. Epithelial-mesenchymal transition, TGF-beta, and osteopontin in wound healing and tissue remodeling after injury. J Burn Care Res. 2012;33:311–8. - PMC - PubMed
    1. Wu M, Schneider DJ, Mayes MD, Assassi S, Arnett FC, Tan FK, et al. Osteopontin in systemic sclerosis and its role in dermal fibrosis. J Invest Dermatol. 2012;132:1605–14. - PMC - PubMed