[Frontiers in Bioscience 13, 2001-2021, January 1, 2008]

Regulation of osteogenic differentiation during skeletal development

Zhong-Liang Deng1,2, Katie A. Sharff2, Ni Tang1,2, Wen-Xin Song2, Jinyong Luo1,2, Xiaoji Luo1,2,, Jin Chen1,2, Erwin Bennett2, Russell Reid2, David Manning2, Anita Xue2, Anthony G. Montag2,3, Hue H. Luu2, Rex C. Haydon2,4 Tong-Chuan He1,2

1Key Laboratory of Diagnostic Medicine designated by Chinese Ministry of Education and the Affiliated Hospitals of Chongqing Medical University, Chongqing 400046, China, 2Molecular Oncology Laboratory, Department of Surgery, The University of Chicago Medical Center, 5841 South Maryland Avenue, MC 3079, Chicago, IL 60637, 3Department of Pathology, The University of Chicago Medical Center, Chicago, IL 60637

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Stem cells and mesenchymal stem cells
4. Mesenchymal stem cell lineages
4.1. Myogenic lineage
4.2. Adipogenic lineage
4.3. Chondrogenic lineage
4.4. Osteogenic lineage
4.5. Reciprocal relationship between osteogenesis and adipogenesis
4.6. Plasticity and directed differentiation of mesenchymal stem cells
5. Major signaling pathways controlling osteogenesis
5.1. Wnt signaling
5.2. TGF beta/BMP superfamily
5.3. Notch signaling
5.4. Hedgehog signaling
5.5. FGF signaling
5.6. Other signaling pathways
6. Transcriptional regulation of osteogenic differentiation
6.1. Runx2
6.2. Osterix
6.3. ATF4
6.4. TAZ
6.5. Post-translational regulation of osteogenic differentiation
6.6. Other regulators of osteogenesis
7. Summary and future directions
8. Acknowledgements
9. References

1. ABSTRACT

Bone formation during skeletal development involves a complex coordination among multiple cell types and tissues. Bone is of crucial importance for the human body, providing skeletal support, and serving as a home for the formation of hematopoietic cells and as a reservoir for calcium and phosphate. Bone is also continuously remodeled in vertebrates throughout life. Osteoblasts and osteoclasts are specialized cells responsible for bone formation and resorption, respectively. Early development of the vertebrate skeleton depends on genes that control the distribution and proliferation of cells from cranial neural crest, sclerotomes, and lateral plate mesoderm into mesenchymal condensations, where cells differentiate to osteoblasts. Significant progress has been made over the past decade in our understanding of the molecular framework that controls osteogenic differentiation. A large number of morphogens, signaling molecules, and transcriptional regulators have been implicated in regulating bone development. A partial list of these factors includes the Wnt/beta-catenin, TGF-beta/BMP, FGF, Notch and Hedgehog signaling pathways, and Runx2, Osterix, ATF4, TAZ, and NFATc1 transcriptional factors. A better understanding of molecular mechanisms behind osteogenic differentiation would not only help us to identify pathogenic causes of bone and skeletal diseases but also lead to the development of targeted therapies for these diseases.