JAK-STAT signaling: molecular mechanism and targeted treatment in dento-maxillofacial abnormalities

TL;DR

This review explores how JAK-STAT signaling influences dento-maxillofacial development and how targeting this pathway could lead to new treatments for related abnormalities.

Contribution

The paper provides a comprehensive review of JAK-STAT signaling's role in dento-maxillofacial development and its potential as a therapeutic target.

Findings

JAK-STAT signaling regulates key processes in dentofacial development, including ossification and enamel formation.

Mutations in JAK-STAT signaling are linked to syndromes with severe dento-maxillofacial abnormalities.

Drugs like baricitinib and imatinib show promise in treating skeletal disorders related to JAK-STAT dysfunction.

Abstract

Dento-maxillofacial abnormalities are highly prevalent and arise as a result of a variety of etiological factors, presenting substantial challenges to treatment. The JAK-STAT signaling plays a pivotal role in dentofacial development, regulating endochondral ossification, intramembranous ossification, dental follicle formation, and enamel development. Mutations in the JAK-STAT signaling lead to syndromes associated with severe dento-maxillofacial abnormalities, including Growth Hormone Insensitivity Syndrome and Autosomal Dominant Hyper-IgE Syndrome. Corresponding mouse disease models have been developed to simulate the phenotypes observed in clinical patients and investigate their underlying mechanism. Meanwhile, several medications targeting JAK-STAT signaling, including baricitinib and imatinib, have been developed for clinical application, demonstrating significant effects in skeletal disorders such as osteoporosis and osteoarthritis, indicating promising effects in development and abnormalities of dento-maxillofacial. In this review, we aim to summarize the role of JAK-STAT signaling in the development and abnormalities of dento-maxillofacial bone, and the relevant molecules that may be utilized for clinical treatment, to shed new light on the precise treatment of dento-maxillofacial abnormalities.

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