title: Bone micro-fragility caused by the mimetic aging processes in α-klotho deficient mice: in situ nanoindentation assessment of dilatational bands.
abstract: The nanoscale structure-function relationship is a key determinant of bone toughness or micro-fragility. The loss of bone toughness during the aging process has been accepted based on empirical evidence, but this concept has not yet been fully supported by evidence at the material level. Here, we demonstrate a reduction in bone toughening mechanism in mimetic aged cortical bone obtained from α-klotho deficient (α-klotho(-/-)) mice and assessed by in situ dynamic mechanical analysis. The strain-rate nanoindentation tests showed enhanced stiffening of the wild-type calvarial bone and a large dimensional recovery during rapid loading following the constant displacement test. Such strain-dependent stiffening was likely associated with nanoscale dilatational bands and subsequent strain-energy transfer to the superior wild-type cross-linked collagen matrix network. The absence of dilatational bands formed by hydroxyapatite crystals and non-collagenous proteins in the α-klotho(-/-) bone samples likely diminished the intrinsic bone toughening mechanisms almost independent of viscoelastic behaviors. Such nanoscale structural alternations that occur during aging processes lead to crack propagation and result in overall bone fractures under large external stresses. In addition, dynamic mechanical analysis using instrumented nanoindentation was useful for the evaluation of bone mechanical properties in this pathological model of a genetic knockout mouse.
authors: Department of Orthodontics, Showa University School of Dentistry, 2-1-1, Kitasenzoku, Ohta-ku, Tokyo 145-8515, Japan.
authors: Noriko
authors: N
authors: Maruyama
authors: Department of Conservative Dentistry, Division of Biomaterials and Engineering, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. Electronic address: yookun@dent.showa-u.ac.jp.
authors: Yo
authors: Y
authors: Shibata
authors: Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Ayako
authors: A
authors: Mochizuki
authors: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Atsushi
authors: A
authors: Yamada
authors: Department of Orthodontics, Showa University School of Dentistry, 2-1-1, Kitasenzoku, Ohta-ku, Tokyo 145-8515, Japan.
authors: Koutaro
authors: K
authors: Maki
authors: Department of Oral Physiology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Tomio
authors: T
authors: Inoue
authors: Department of Biochemistry, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Ryutaro
authors: R
authors: Kamijo
authors: Department of Conservative Dentistry, Division of Biomaterials and Engineering, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
authors: Takashi
authors: T
authors: Miyazaki
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001696:Biomechanical Phenomena; D001842:Bone and Bones / Q000473:pathology*; D003094:Collagen / Q000737:chemistry; D003460:Crystallization; D017886:Durapatite / Q000737:chemistry; D004548:Elasticity; D050723:Fractures, Bone / Q000473:pathology / Q000517:prevention & control; D005966:Glucuronidase / Q000235:genetics* / Q000502:physiology*; D000090265:Klotho Proteins; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013059:Spectrum Analysis, Raman; D013314:Stress, Mechanical
chemical_list: D001672:Biocompatible Materials; D003094:Collagen; D017886:Durapatite; D005966:Glucuronidase; D000090265:Klotho Proteins
keywords: Ageing; Bone; Dynamic mechanical analysis; Mechanical properties; Nanoindentation