title: Expression pattern of the chromosome 21 transcription factor Ets2 in cell-seeded three-dimensional bone constructs.
abstract: The ability to generate new bone for reconstructive surgery use is a major clinical need. Tissue engineering with osteoprogenitor cells isolated from the patient's periosteum and seeded into bioresorbable scaffolds offers a promising approach to the generation of skeletal tissue. To our knowledge, there is no description about the expression of Ets2 in tissue engineered "bone neotissue." The aim of our study was to manufacture cell-seeded three-dimensional bone constructs with human periosteal cells on poly (lactic-co-glycolic acid) polymer fleeces to describe the expression pattern of Ets2 and its target genes osteocalcin and osteopontin; expression analysis of type I collagen, core-binding factor-1, alkaline phosphatase, and osteonectin; the ability of matrix mineralization and ALP enzymatic activity showed the osteogenic character of the constructs. A significant correlation between the expression of Ets2 and osteopontin mRNA (r = -0.70; p < 0.05) could be shown. A 1.35-fold increase of Ets2 expression from days 1 to 9 was detected, followed by a slight decrease from days 11 to 15. Until the end of the culture period, the expression of Ets2 reached a comparable high level as detected on day 9. In contrast, the expression level of osteopontin mRNA reached a maximum at day 7, followed by a progressive 3.04-fold decrease until day 21. This study shows for the first time that Ets2 gene and its transcriptional target genes are expressed in tissue-engineered bone constructs. These findings have the potential to provide much-needed information about the role and function of Ets2 in human osteogenesis processes and creation of "bone neotissue."
authors.affiliation: Department of Cranio-Maxillofacial and Oral Surgery, Medical University of Vienna, Vienna, Austria. dritan.turhani@meduniwien.ac.at
authors.forename: Dritan
authors.initials: D
authors.lastname: Turhani
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Watzinger
authors.forename: Martina
authors.initials: M
authors.lastname: Weissenböck
authors.forename: Kaan
authors.initials: K
authors.lastname: Yerit
authors.forename: Barbara
authors.initials: B
authors.lastname: Cvikl
authors.forename: Rolf
authors.initials: R
authors.lastname: Ewers
authors.forename: Dietmar
authors.initials: D
authors.lastname: Thurnher
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001672:Biocompatible Materials / Q000737:chemistry*; D018786:Bone Substitutes / Q000737:chemistry*; D001842:Bone and Bones / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D002891:Chromosomes, Human, Pair 21; D050660:Core Binding Factors; D017931:DNA Primers / Q000737:chemistry; D005786:Gene Expression Regulation; D006016:Glycolates / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008648:Mesoderm / Q000166:cytology / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D009363:Neoplasm Proteins / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D015675:Osteocalcin / Q000737:chemistry / Q000378:metabolism; D010012:Osteogenesis; D015676:Osteonectin / Q000737:chemistry; D053495:Osteopontin; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012795:Sialoglycoproteins / Q000737:chemistry; D013997:Time Factors; D023822:Tissue Engineering; D015534:Trans-Activators / Q000096:biosynthesis*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D018786:Bone Substitutes; D050660:Core Binding Factors; D017931:DNA Primers; C494069:ETS2 protein, human; D006016:Glycolates; D009363:Neoplasm Proteins; D015676:Osteonectin; D011108:Polymers; D050787:Proto-Oncogene Protein c-ets-2; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D015534:Trans-Activators; D014157:Transcription Factors; D015675:Osteocalcin; D053495:Osteopontin; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000469:Alkaline Phosphatase