title: Genetic evidence for the vital function of Osterix in cementogenesis.
abstract: To date, attempts to regenerate a complete tooth, including the critical periodontal tissues associated with the tooth root, have not been successful. Controversy still exists regarding the origin of the cell source for cellular cementum (epithelial or mesenchymal). This disagreement may be partially due to a lack of understanding of the events leading to the initiation and development of the tooth roots and supportive tissues, such as the cementum. Osterix (OSX) is a transcriptional factor essential for osteogenesis, but its role in cementogenesis has not been addressed. In the present study, we first documented a close relationship between the temporal- and spatial-expression pattern of Osx and the formation of cellular cementum. We then generated 3.6-kilobase (kb) collagen type I (3.6-kb Col 1)-Osx transgenic mice, which displayed accelerated cementum formation versus wild-type (WT) controls. Importantly, the conditional deletion of Osx in the mesenchymal cells with two different Cre systems (the 2.3-kb Col 1 and an inducible CAG-Cre estrogen receptor [CreER]) led to a sharp reduction in cellular cementum formation (including the cementum mass and mineral deposition rate) and gene expression of dentin matrix protein 1 (DMP1) by cementocytes. However, the deletion of the Osx gene after cellular cementum formed did not alter the properties of the mature cementum as evaluated by backscattered scanning electron microscopy (SEM) and resin-casted SEM. Transient transfection of Osx in the cementoblasts in vitro significantly inhibited cell proliferation and increased cell differentiation and mineralization. Taken together, these data support: (1) the mesenchymal origin of cellular cementum (from periodontal ligament [PDL] progenitor cells); (2) the vital role of OSX in controlling the formation of cellular cementum; and (3) the limited remodeling of cellular cementum in adult mice.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST), Ministry of Education, Department of Periodontology, School and Hospital of Stomatology, Wuhan University, Wuhan, China. jfeng@bcd.tamhsc.edu
authors.forename: Zhengguo
authors.initials: Z
authors.lastname: Cao
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Xianglong
authors.initials: X
authors.lastname: Han
authors.forename: Yinshi
authors.initials: Y
authors.lastname: Ren
authors.forename: Tian
authors.initials: T
authors.lastname: Gao
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
authors.forename: Benoit
authors.initials: B
authors.lastname: de Crombrugghe
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Somerman
authors.forename: Jian Q
authors.initials: JQ
authors.lastname: Feng
mesh_terms: D000818:Animals; D002460:Cell Line; D025021:Cementogenesis / Q000235:genetics*; D003739:Dental Cementum / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D016133:Polymerase Chain Reaction; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D000076182:Sp7 Transcription Factor; C479466:Sp7 protein, mouse; D014157:Transcription Factors