title: Leader genes in osteogenesis: a theoretical study.
abstract: Little is still known about the molecular mechanisms involved in the process of osteogenesis. In this paper, the leader genes approach, a new bioinformatics method which has already been experimentally validated, is adopted in order to identify the genes involved in human osteogenesis. Interactions among genes are then calculated and genes are ranked according to their relative importance in this process. In total, 167 genes were identified as being involved in osteogenesis. Genes were divided into 4 groups, according to their main function in the osteogenic processes: skeletal development; cell adhesion and proliferation; ossification; and calcium ion binding. Seven genes were consistently identified as leader genes (i.e. the genes with the greatest importance in osteogenesis), while 14 were found to have slightly less importance (class B genes). It was interesting to notice that the larger part of leader and class B genes belonged to the cell adhesion and proliferation or to the ossification sub-groups. This finding suggested that these two particular sub-processes could play a more important role in osteogenesis. Moreover, among the 7 leader genes, it is interesting to notice that RUNX2, BMP2, SPARC, PTH play a direct role in bone formation, while the 3 other leader genes (VEGF, IL6, FGF2) seem to be more connected with an angiogenetic process. Twenty-nine genes have no known interactions (orphan genes). From these results, it may be possible to plan an ad hoc experimentation, for instance by microarray analyses, focused on leader, class B and orphan genes, with the aim to shed new light on the molecular mechanisms underlying osteogenesis.
authors.affiliation: Laboratories of Biophysics and Nanobiotechnology, Department of Medical Science, University of Genova, Italy. b_orlando@virgilio.it
authors.forename: Bruno
authors.initials: B
authors.lastname: Orlando
authors.forename: Luca
authors.initials: L
authors.lastname: Giacomelli
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Ricci
authors.forename: Antonio
authors.initials: A
authors.lastname: Barone
authors.forename: Ugo
authors.initials: U
authors.lastname: Covani
mesh_terms: D001846:Bone Development / Q000235:genetics; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002448:Cell Adhesion / Q000235:genetics; D049109:Cell Proliferation; D002874:Chromosome Mapping; D019295:Computational Biology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D030541:Databases, Genetic; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D008957:Models, Genetic; D005810:Multigene Family / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics*; D015676:Osteonectin; D010281:Parathyroid Hormone / Q000235:genetics; D010641:Phenotype; D025521:Tumor Suppressor Proteins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D015850:Interleukin-6; D015676:Osteonectin; D010281:Parathyroid Hormone; C493709:RUNX2 protein, human; C577241:SPARC protein, human; D025521:Tumor Suppressor Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D002118:Calcium