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

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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Funding

National Natural Science Foundation of China (National Science Foundation of China)(82430032)

National Key Research and Development Program of China (2024YFC2510701); the 18th Innovation Training Program of Shanghai Jiao Tong University School of Medicine (1824504); Shanghai Jiao Tong University 2024 Undergraduate Entrepreneurship Training Program (202410248037X); the National Science Foundation of Shanghai (21ZR1436900,22ZR1436700); Shanghai's Top Priority Research Center (2022ZZ01017); the Hainan Provincial Natural Science Foundation of China (824MS152) ; the Cross-Disciplinary Research Fund of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (JYJC202116); the Biomaterials and Regenerative Medicine Institute Cooperative Research Project Shanghai Jiao Tong University School of Medicine (2022LHB02); the Project of Biobank of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine·(YBKB202216); the Original Exploration Project of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine(JYYC003), and Two-Hundred Talent Project of Shanghai Jiao Tong University School of Medicine (20221809); the Fundamental Research Funds for the Central Universities (YG2023ZD14); Shanghai Science and Technology Innovation Action Plan-International Science and Technology Cooperation Program(23410713600).

RIGHTS & PERMISSIONS

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