Patterns & Phenotypes
Systems level analysis of osteoclastogenesis reveals intrinsic and extrinsic regulatory interactions
Article first published online: 21 JUN 2007
Copyright © 2007 Wiley-Liss, Inc.
Volume 236, Issue 8, pages 2181–2197, August 2007
How to Cite
Kiesel, J., Miller, C., Abu-Amer, Y. and Aurora, R. (2007), Systems level analysis of osteoclastogenesis reveals intrinsic and extrinsic regulatory interactions. Dev. Dyn., 236: 2181–2197. doi: 10.1002/dvdy.21206
- Issue published online: 25 JUL 2007
- Article first published online: 21 JUN 2007
- Manuscript Accepted: 23 APR 2007
- National Science Foundation. Grant Number: EF 0425749
- developmental program;
- coexpression networks;
- RANK ligand;
- systems biology
Osteoclasts are bone-resorbing cells derived from the myeloid lineage that play a central role in bone remodeling and inflammatory bone erosion diseases. The receptor activator of NF-κB ligand (RANKL) produced by osteoblasts and activated immune cells initiates the development of osteoclasts in the bone marrow. Using time series gene expression data, the intrinsic processes and the extrinsic factors that control osteoclastogenesis were identified. The gene expression profiles display distinct commitment and differentiation phases. Analysis of the time course revealed several mechanistic details, including the complex role of cholesterol in osteoclast development. Epistatic interactions and the coordination between cellular processes that regulate development were inferred from the coexpression network. The coexpression network indicated that osteoclasts induce angiogenesis and recruit T-cells to the site of osteoclastogenesis early in the commitment phase. The resulting model provides an essential framework for a better understanding of the epigenetic program of osteoclastogenesis. Developmental Dynamics 236:2181–2197, 2007. © 2007 Wiley-Liss, Inc.