title: Screening for potential genes associated with bone overgrowth after mid-shaft femur fracture in a rat model.
abstract: BACKGROUND
  We investigated the underlying molecular mechanisms of bone overgrowth after femoral fracture by using high-throughput bioinformatics approaches.
  
  
  METHODS
  The gene expression profile of GSE3298 (accession number) was obtained from the Gene Expression Omnibus database. Sixteen femoral growth plate samples, including nine samples without fracture and seven fracture samples for seven time points, were used for analysis. The Limma package was applied to identify differentially expressed genes (DEGs) between fractured and intact samples. The DAVID online tool was used for Gene ontology functional and pathway enrichment analysis. A protein-protein interaction (PPI) network established by String software was used to identify interactions between significant DEGs, and network modules were detected using plug-in MCODE. Additionally, a transcription regulatory network was constructed based on the ENCODE Project and PPI network.
  
  
  RESULTS
  A total of 680 DEGs were screened in fractured femoral growth plate samples compared with controls, including 238 up- and 442 down-regulated genes. These DEGs were significantly involved in the calcium signaling pathway and cancer pathway. A PPI network was constructed with 167 nodes and 233 edges, and module analysis demonstrated that CCL2, CSF2, NOS2, and DLC1 may stimulate bone overgrowth after femoral fracture via anti-apoptosis-related functions. A transcription regulatory network was constructed with 387 interacting pairs, and overlapping nodes were significantly enriched in intracellular signaling cascade and regulation of cell proliferation, among others.
  
  
  CONCLUSIONS
  Bone overgrowth was associated with changes in the expression of identified DEGs such as CCL2, NOS2, CSF2, and DLC1 in the femoral head. They may be important in regulating bone overgrowth via the anti-apoptosis of osteoblasts.
authors.affiliation: The Second Hospital of Jilin University, Ziqiang St 218 Nan Guan District, Changchun, 130041, China.
authors.forename: Chibing
authors.initials: C
authors.lastname: Liu
authors.affiliation: Jilin University, Changchun, 130012, China.
authors.forename: Yanting
authors.initials: Y
authors.lastname: Liu
authors.affiliation: China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, China.
authors.forename: Weizhong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: The Six Affiliated Hospital of Xinjiang Medical University Medical Examination Center, Autonomous Region, Five Star South Road, No. 39, Urumqi City, Xinjiang Uygur, 830002, China. liuqyqyu@sina.com.
authors.forename: Xiuxin
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D016723:Bone Remodeling / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D030541:Databases, Genetic; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D005269:Femur / Q000254:growth & development* / Q000378:metabolism; D017102:Fracture Healing / Q000235:genetics / Q000502:physiology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006132:Growth Plate / Q000254:growth & development; D060066:Protein Interaction Maps; D051381:Rats
keywords: Femoral fracture; Module; Overgrowth; Protein-protein interaction network