title: Mutations in COL1A1 Gene Change Dentin Nanostructure.
abstract: Although many studies have attempted to associate specific gene mutations with dentin phenotypic severity, it remains unknown how the mutations in COL1A1 gene influence the mechanical behavior of dentin collagen and matrix. Here, we reported one osteogenesis imperfecta (OI) pedigree caused by two new inserting mutations in exon 5 of COL1A1 (NM_000088.3:c.440_441insT;c.441_442insA), which resulted in the unstable expression of COL1A1 mRNA and half quantity of procollagen production. We investigated the morphological and mechanical features of proband's dentin using atomic force microscope (AFM), scanning electron microscope, and transmission electron microscope. Increased D-periodic spacing, variably enlarged collagen fibrils coating with fewer minerals were found in the mutated collagen. AFM analysis demonstrated rougher dentin surface and sparsely decreased Young's modulus in proband's dentin. We believe that our findings provide new insights into the genetic-/nano- mechanisms of dentin diseases, and may well explain OI dentin features with reduced mechanical strength and a lower crosslinked density.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology Clinic of Oral Rare Diseases and Genetic Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology Clinic of Oral Rare Diseases and Genetic Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Zhenxia
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Prosthodontics School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Yunna
authors.initials: Y
authors.lastname: Gan
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav WiedsVej 14, Aarhus C, Denmark.
authors.forename: Dan
authors.initials: D
authors.lastname: Xia
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav WiedsVej 14, Aarhus C, Denmark.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology Clinic of Oral Rare Diseases and Genetic Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Oral Biology Clinic of Oral Rare Diseases and Genetic Diseases, The Fourth Military Medical University, Xi'an, Shaanxi, People's Republic of China.
authors.forename: Jiaji
authors.initials: J
authors.lastname: Yang
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav WiedsVej 14, Aarhus C, Denmark.|Department of Oral and Maxillofacial Surgery, School of Stomatology, Central South University, Changsha, Hunan, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Gustav WiedsVej 14, Aarhus C, Denmark.
authors.forename: Mingdong
authors.initials: M
authors.lastname: Dong
mesh_terms: D000328:Adult; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D003804:Dentin / Q000378:metabolism / Q000473:pathology*; D055119:Elastic Modulus; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation / Q000235:genetics*; D049329:Nanostructures / Q000737:chemistry*; D010013:Osteogenesis Imperfecta / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain
keywords: atomic force microscopy; collagen; dentin; mutation; osteogenesis imperfecta