title: In situ gene expression analysis during BMP2-induced ectopic bone formation in mice shows simultaneous endochondral and intramembranous ossification.
abstract: We examined the molecular progression of ectopic bone development upon application of recombinant human bone morphogenetic protein-2 (rhBMP2), using a commercial collagen type I carrier, in the hind quarter muscles of mice. We performed a gene expression study using mRNA in situ hybridisation to compare embryonic cartilage and bone formation with BMP2-induced ectopic bone formation. As bone growth can be induced postnatally or in adult animals, we examined the expression of molecules regulating embryonic bone development. We found that the mRNAs of the same molecules, such as Indian hedgehog (IHH), parathyroid hormone (PTH)/PTH-related peptide receptor (PPR) and BMPs, that regulate embryonic cartilage and bone development, are expressed during BMP-induced ectopic bone formation, suggesting parallels in the mechanisms controlling these processes. Our studies support by molecular means the previous findings in rats that BMP2-induced ectopic bone formation in mice undergoes bone development involving both modes, endochondral and intramembranous ossification, simultaneously at different sites of the implant.
authors.affiliation: GSF Research Center Institute of Mammalian Genetics, Ingolstädter Landrtr. 1, D-85764 Neuherberg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Stoeger
authors.forename: Gabriele E
authors.initials: GE
authors.lastname: Proetzel
authors.forename: Heike
authors.initials: H
authors.lastname: Welzel
authors.forename: Apollon
authors.initials: A
authors.lastname: Papadimitriou
authors.forename: Carola
authors.initials: C
authors.lastname: Dony
authors.forename: Rudi
authors.initials: R
authors.lastname: Balling
authors.forename: Clementine
authors.initials: C
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D053823:Hedgehog Proteins; D006801:Humans; D017403:In Situ Hybridization; D051379:Mice; D009999:Ossification, Heterotopic / Q000139:chemically induced / Q000196:embryology / Q000209:etiology* / Q000235:genetics*; D010281:Parathyroid Hormone / Q000235:genetics; D044162:Parathyroid Hormone-Related Protein / Q000235:genetics; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics; D016212:Transforming Growth Factor beta
chemical_list: C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D053823:Hedgehog Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D012333:RNA, Messenger; D011994:Recombinant Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2