Lysyl oxidase like-2 reinforces unsatisfactory ossification induced by bone morphogenetic protein-2: Relating nanomechanical properties and molecular changes

• Published in: Nanomedicine Vol. 9; no. 7; pp. 1036 - 1047
• Main Authors: Shibata, Yo, PhD, Suzuki, Dai, PhD, Wurihan, BDS, Yamada, Atsushi, PhD, Maruyama, Noriko, DDS, Fujisawa, Naoki, PhD, Kamijo, Ryutaro, PhD, Miyazaki, Takashi, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2013
• Subjects: Amino Acid Oxidoreductases - pharmacology; Animals; Bone Morphogenetic Protein 2 - pharmacology; Bone morphogenetic protein-2; Calcification, Physiologic - drug effects; Cells, Cultured; DNA microarray; Gene Expression Profiling; Internal Medicine; Lysyl oxidase like-2; Male; Mechanical Phenomena - drug effects; Mice; Nanoindentation; Nanoparticles - chemistry; Oligonucleotide Array Sequence Analysis; Osteoblasts; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteogenesis - drug effects; Raman spectroscopy; Recombinant Proteins - pharmacology; Spectrum Analysis, Raman; Transforming Growth Factor beta - pharmacology; DNA microarray; Bone morphogenetic protein-2; Raman spectroscopy; Osteoblasts; Lysyl oxidase like-2; Nanoindentation
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2013.04.008

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. From the Clinical Editor 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.