[Frontiers in Bioscience 13, 2842-2865, January 1, 2008]

FGF signaling: its role in bone development and human skeleton diseases

Nan Su, XiaoLan Du, Lin Chen

State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, China

TABLE OF CONTENTS

1. Abstract
2. Introduction of skeleton development
3. Introduction of FGFs/FGFRs
4. FGFs/FGFRs signaling in chondrodysplasia, craniosynostosis and other human genetic bone diseases
4.1. Introduction of chondrodysplasia and craniosynostosis
4.2. FGFR3 and chondrodysplasia
4.3. FGFRs and craniosynostosis
4.4. Other FGFs/FGFRs-related genetic diseases with abnormal skeleton development
4.5. FGF23 and dysregulated phosphate metabolism
5. Mechanism of FGFs/FGFRs in bone development and genetic diseases
5.1. Role of FGFs/FGFRs in endochondral ossification
5.1.1. FGFs/FGFRs expression
5.1.2. Role of FGFs/FGFRs in endochondral ossification
5.2. FGFR3 in chondrodysplasia
5.3. The role of FGFs/FGFRs in intramembranous ossification
5.3.1. FGFs/FGFRs expression
5.3.2. FGFs/FGFRs signaling in intramembranous ossification
5.4. FGFRs in craniosynostosis
6. Perspectives
7. Acknowledgements
8. References

1. ABSTRACT

Fibroblast growth factors (FGFs)/Fibroblast growth factor receptors (FGFRs) signaling has recently been found to play very important roles in bone development and diseases. Missense mutations in several FGFs and FGFRs were found in human to cause a variety of congenital bone diseases including chondrodysplasia syndromes, craniosynostosis syndromes, and syndromes with dysregulated phosphate metabolism, etc. In addition to its role in bone development and genetic diseases, FGF signaling is also involved in the maintenance of adult bone homeostasis and fracture healing, etc. Understanding the underlying molecular mechanisms for the role of FGFs/FGFRs in the regulation of bone development and diseases will ultimately lead to better prevention and treatment of FGF signaling-related bone diseases. In this review, we are going to give a summary of the role of FGFs/FGFRs in skeleton development and diseases, and pay more attention to those recent progresses.