title: Lysyl oxidase like-2 reinforces unsatisfactory ossification induced by bone morphogenetic protein-2: relating nanomechanical properties and molecular changes.
abstract: Bone morphogenetic protein-2 (BMP2) is among the most popular anabolic agents and substantially increase bone volume related to enhanced osteoblast differentiation. Here we demonstrate a remarkable deterioration in the nanomechanical properties of mineralized tissue induced from osteoblasts solely by the function of BMP2. Mineralized tissue of primary osteoblasts cultured with BMP2 shows molecular features of both bone and cartilage, but depletion of lysyl oxidase family members leads to poor nanomechanical properties of the mineralized tissue. Lysyl oxidase like-2 supplementation reinforces the inferior mineralized tissue induced from osteoblasts by BMP2 through intermolecular cross-linking of type II or type X collagen-rich extracellular matrix. This may also mimic a consolidation of bone fracture gaps, despite the fact that the distribution of the bone properties in such microenvironments has been poorly elucidated. These findings confirm the importance of testing newly induced bone down to the microscale and nanoscale in bone tissue engineering.
  
  
  BACKGROUND
  Bone morphogenetic protein-2 is known to substantially increase bone volume related to enhanced osteoblast differentiation; however, this team of investigators report a remarkable deterioration in the nanomechanical properties of mineralized tissue induced from osteoblasts solely by the function of BMP2.
authors: Department of Conservative Dentistry, Division of Biomaterials and Engineering, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo, Japan. Electronic address: yookun@dent.showa-u.ac.jp.
authors: Yo
authors: Y
authors: Shibata
authors: Dai
authors: D
authors: Suzuki
authors: Wurihan
authors: Atsushi
authors: A
authors: Yamada
authors: Noriko
authors: N
authors: Maruyama
authors: Naoki
authors: N
authors: Fujisawa
authors: Ryutaro
authors: R
authors: Kamijo
authors: Takashi
authors: T
authors: Miyazaki
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000494:pharmacology*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D002113:Calcification, Physiologic / Q000187:drug effects; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D008297:Male; D055595:Mechanical Phenomena / Q000187:drug effects*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D013059:Spectrum Analysis, Raman; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D055396:Bone Morphogenetic Protein 2; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human
keywords: Bone morphogenetic protein-2; DNA microarray; Lysyl oxidase like-2; Nanoindentation; Osteoblasts; Raman spectroscopy