title: Type VII collagen deficiency causes defective tooth enamel formation due to poor differentiation of ameloblasts.
abstract: Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in the gene encoding type VII collagen (COL7), a major component of anchoring fibrils in the epidermal basement membrane zone. Patients with RDEB present a low oral hygiene index and prevalent tooth abnormalities with caries. We examined the tooth enamel structure of an RDEB patient by scanning electron microscopy. It showed irregular enamel prisms, indicating structural enamel defects. To elucidate the pathomechanisms of enamel defects due to COL7 deficiency, we investigated tooth formation in Col7a1(-/-) and COL7-rescued humanized mice that we have established. The enamel from Col7a1(-/-) mice had normal surface structure. The enamel calcification and chemical composition of Col7a1(-/-) mice were similar to those of the wild type. However, transverse sections of teeth from the Col7a1(-/-) mice showed irregular enamel prisms, which were also observed in the RDEB patient. Furthermore, the Col7a1(-/-) mice teeth had poorly differentiated ameloblasts, lacking normal enamel protein-secreting Tomes' processes, and showed reduced mRNA expression of amelogenin and other enamel-related molecules. These enamel abnormalities were corrected in the COL7-rescued humanized mice expressing a human COL7A1 transgene. These findings suggest that COL7 regulates ameloblast differentiation and is essential for the formation of Tomes' processes. Collectively, COL7 deficiency is thought to disrupt epithelial-mesenchymal interactions, leading to defective ameloblast differentiation and enamel malformation in RDEB patients.
authors.affiliation: Department of Dermatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Umemoto
authors.forename: Masashi
authors.initials: M
authors.lastname: Akiyama
authors.forename: Takanori
authors.initials: T
authors.lastname: Domon
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Nomura
authors.forename: Satoru
authors.initials: S
authors.lastname: Shinkuma
authors.forename: Kei
authors.initials: K
authors.lastname: Ito
authors.forename: Takuya
authors.initials: T
authors.lastname: Asaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawamura
authors.forename: Jouni
authors.initials: J
authors.lastname: Uitto
authors.forename: Motohiro
authors.initials: M
authors.lastname: Uo
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimizu
mesh_terms: D000565:Ameloblasts / Q000378:metabolism / Q000473:pathology*; D000566:Amelogenesis; D000818:Animals; D002113:Calcification, Physiologic; D002454:Cell Differentiation; D002648:Child; D024143:Collagen Type VII / Q000172:deficiency* / Q000378:metabolism; D003743:Dental Enamel / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D016108:Epidermolysis Bullosa Dystrophica / Q000473:pathology / Q000503:physiopathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008954:Models, Biological; D010641:Phenotype; D014070:Tooth / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure
chemical_list: C569053:COL7A1 protein, human; D024143:Collagen Type VII