title: Synchronous disruption of anisotropic arrangement of the osteocyte network and collagen/apatite in melanoma bone metastasis.
abstract: Cancer metastasis to bones increases the risk of fragility fracture by altering bone metabolism and disrupting bone structure. Osteocytes, which organize a dense network that is closely linked with the circumambient matrix, play a key role in regulation of bone microstructure and material properties. The aim of this study was to elucidate the influence of cancer metastasis on the organization of the osteocyte network and collagen/biological apatite (BAp) microstructure in the context of osteocyte/matrix coupling. Using a mouse model intracardially injected with B16F10 melanoma cells or vehicle, the geometric and metabolic changes to osteocytes were analyzed by nano-computed tomography (nano-CT) and histology, and the alignment of collagen fibrils and BAp was analyzed by birefringence measurement and microbeam-X-ray diffraction, respectively. The material properties of bones were further analyzed with nanoindentation method. These experiments revealed that the osteocyte network was markedly disorganized in cancer-bearing bone tissues. The osteocytes showed a variety of residing states in the lacunae; some lacunae were osteolytic while some were replete with immature matrix, suggesting significant disruption in osteocyte/matrix coupling. Collagen/BAp microstructure was also disorganized in cancer-bearing bones as observed by significant decreases in the preferential alignment of both collagen fibrils and BAp; the latter was further shown to be significantly correlated with Young's modulus. The present study revealed that the disruption in the arrangement of the osteocyte network and collagen/BAp microstructure and the deterioration of mechanical function occurred synchronously during cancer bone metastasis.
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Aiko
authors.initials: A
authors.lastname: Sekita
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Aira
authors.initials: A
authors.lastname: Matsugaki
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Ishimoto
authors.affiliation: Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita, Osaka 565-0871, Japan. Electronic address: nakano@mat.eng.osaka-u.ac.jp.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000818:Animals; D001031:Apatites / Q000378:metabolism*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000556:secondary*; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D055119:Elastic Modulus; D005260:Female; D008545:Melanoma / Q000150:complications* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010011:Osteocytes / Q000378:metabolism*; D014961:X-Ray Diffraction; D055114:X-Ray Microtomography
chemical_list: D001031:Apatites; D003094:Collagen
keywords: Anisotropic arrangement; Biological apatite; Cancer bone metastasis; Collagen fibrils; Melanoma; Osteocyte network