Thoughts on the Etiology of Cherubism

Cherubism is nowadays classified as an autoimmune disease and was first described in 1933. Although suspected at that time to be the result of defective tooth development, it was primarily classified as a bone disease caused by a mutation in the gene. Despite a knock-in mouse model, phenotypic signs...

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Bibliographic Details
Published in:Journal of clinical medicine 2024-04, Vol.13 (7), p.2082
Main Authors: Hyckel, Peter, Liehr, Thomas
Format: Article
Language:English
Subjects:
Bone diseases
Extracellular matrix
Hominids
Immunology
Jaw
Molecular biology
Morphogenesis
Mutation
Pathogenesis
Signal transduction
Teeth
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Summary:Cherubism is nowadays classified as an autoimmune disease and was first described in 1933. Although suspected at that time to be the result of defective tooth development, it was primarily classified as a bone disease caused by a mutation in the gene. Despite a knock-in mouse model, phenotypic signs in the jaw area were not reproducible in this model. The features of classical cherubism can be attributed to a disturbed formation of the dental placode of the second molar. Since 2019, it has become clear that inhibition of the WNT pathway leads to the accumulation of SH3BP2 via tankyrase inhibition. As the dental placode is triggered via WNT (in epithelia) and MSX1 (in mesenchyme), aplasia of the second and third molars occurs due to a block in the WNT pathway. The mesenchymal part, which occurs prior to the body plan regulation of the WNT/MSX1 pathway, remains unaffected and provides the substrate for the giant cell granuloma. Considering macrophage polarization and the role of the extracellular matrix in general, cherubism is situated in the field of tension between autoimmune diseases and cancer. In this sense, we see the cause of cherubism in a WNT-related dysregulation, which can be proven postnatally in the neural crest-related tooth development of the replacement tooth ridge, both genotypically and phenotypically.
ISSN:2077-0383
2077-0383
DOI:10.3390/jcm13072082