A systems biology approach to the identification and analysis of transcriptional regulatory networks in osteocytes

Background: The osteocyte is a type of cell that appears to be one of the key endocrine regulators of bone metabolism and a key responder to initiate bone formation and remodeling. Identifying the regulatory networks in osteocytes may lead to new therapies for osteoporosis and loss of bone. Results: Using microarray, we identified 269 genes over-expressed in osteocyte, many of which have known functions in bone and muscle differentiation and contractility. We determined the evolutionarily conserved and enriched TF binding sites in the 5 kb promoter regions of these genes. Using this data, a transcriptional regulatory network was constructed and subsequently partitioned to identify cis-regulatory modules. Conclusion: Our results show that many osteocyte-specific genes, including two well-known osteocyte markers DMP1 and Sost, have highly conserved clustering of muscle-related cis-regulatory modules, thus supporting the concept that a muscle-related gene network is important in osteocyte biology and may play a role in contractility and dynamic movements of the osteocyte.