Transforming growth factor-[beta]1/Smad/connective tissue growth factor axis: the main pathway in radiation-induced fibrosis of osteoradionecrosis?

Introduction: Osteoradionecrosis (ORN) of the mandible is a serious complication following radiation therapy for malignancies of the head and neck. Radiation-induced fibrosis (RIF) is a new theory that accounts for the damage to normal tissues after radiotherapy, and the radiation-induced fibroatrop...

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Published inDental hypotheses Vol. 4; no. 4; p. 122
Main Authors Zhuang, Qian Wei, Zhang, Zhi Yuan, Liu, Guang Long, Fu, Shui Ting, He, Yue
Format Journal Article
LanguageEnglish
Published Westerly Dental Hypotheses 01.10.2013
Medknow Publications & Media Pvt. Ltd
Subjects
Bones
Causes of
Collagen
Complications and side effects
Connective tissues
Cytokines
Fibrosis
Gene expression
Hypotheses
Hypoxia
Kinases
Necrosis
Physiological aspects
Proteins
Radiotherapy
Signal transduction
Thrombosis
Transforming growth factors
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Summary:Introduction: Osteoradionecrosis (ORN) of the mandible is a serious complication following radiation therapy for malignancies of the head and neck. Radiation-induced fibrosis (RIF) is a new theory that accounts for the damage to normal tissues after radiotherapy, and the radiation-induced fibroatrophic mechanism includes the free-radical formation, endothelial dysfunction, inflammation, microvascular thrombosis, fibrosis and remodeling, and finally bone and tissue necrosis. The Hypothesis: Previous studies revealed that transforming growth factor-[beta]1 (TGF-[beta]1) is the master switch cytokine responsible for the regulation of fibroblast proliferation and differentiation that result in RIF. Among the targets of TGF-[beta]1, connective tissue growth factor (CTGF) is a downstream mediator through the Smad3/4 pathway and plays an important role in connective tissue homeostasis and fibroblast proliferation. Studies have proved that the TGF-[beta]1/Smad/CTGF signaling pathway is involved in the RIF of soft tissues, so the authors put forward a hypothesis that the TGF-[beta]1/Smad/CTGF axis is also the main pathway in RIF of ORN. Evaluation of the Hypothesis: The validation of our hypothesis may provide new insights for better understanding the pathogenesis of ORN and open new perspectives for anti-fibrotic therapies, and pioneer novel approaches to treat ORN. Key words: Connective tissue growth factor, osteoradionecrosis, radiation-induced fibrosis, transforming growth factor- [beta]1/Smad/connective tissue growth factor axis, transforming growth factor-[beta]1
ISSN:2155-8213
2155-8213
DOI:10.4103/2155-8213.122673