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Localization of Minodronate in Mouse Femora Through Isotope Microscopy

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Title: Localization of Minodronate in Mouse Femora Through Isotope Microscopy
Other Titles: Localization of minodronate in bone
Authors: Hongo, Hiromi Browse this author
Sasaki, Muneteru Browse this author
Kobayashi, Sachio Browse this author
Hasegawa, Tomoka Browse this author
Yamamoto, Tomomaya Browse this author
Tsuboi, Kanako Browse this author
Tsuchiya, Erika Browse this author
Nagai, Tomoya Browse this author
Khadiza, Naznin Browse this author
Abe, Miki Browse this author
Kudo, Ai Browse this author
Oda, Kimimitsu Browse this author →KAKEN DB
Henrique Luiz de Freitas, Paulo Browse this author
Li, Minqi Browse this author →KAKEN DB
Yurimoto, Hisayoshi Browse this author →KAKEN DB
Amizuka, Norio Browse this author →KAKEN DB
Keywords: minodronate
isotope microscopy
Issue Date: Oct-2016
Publisher: SAGE Publications
Journal Title: Journal of Histochemistry & Cytochemistry
Volume: 64
Issue: 10
Start Page: 601
End Page: 622
Publisher DOI: 10.1369/0022155416665577
PMID: 27666429
Abstract: Minodronate is highlighted for its marked and sustained effects on osteoporotic bones. To determine the duration of minodronate’s effects, we have assessed the localization of the drug in mouse bones through isotope microscopy, after labeling it with a stable nitrogen isotope (15N-minodronate). In addition, minodronate-treated bones were assessed by histochemistry and TEM. Eight-weeks-old male ICR mice received 15N-minodronate (1mg/kg) intravenously and were sacrificed after three hours, 24 hrs, one week and one month. Isotope microscopy showed that 15N-minodronate was present mainly beneath osteoblasts rather than nearby osteoclasts. At 3 hrs after minodronate administration, histochemistry and TEM showed osteoclasts with well-developed ruffled borders. However, osteoclasts were roughly attached to the bone surfaces and did not feature ruffled borders at 24 hrs after minodronate administration. The numbers of TRAP-positive osteoclasts and ALP-reactive osteoblastic area were not reduced suddenly, and apoptotic osteoclasts appeared in 1 week and 1 month after the injections. Von Kossa staining demonstrated that osteoclasts treated with minodronate did not incorporate mineralized bone matrix. Taken together, minodronate accumulates in bone underneath osteoblasts rather than under bone-resorbing osteoclasts; therefore, it is likely that the minodronate-coated bone matrix is resistant to osteoclastic resorption, which results in a long-lasting and bone-preserving effect.
Type: article (author version)
Appears in Collections:歯学院・歯学研究院 (Graduate School of Dental Medicine / Faculty of Dental Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 網塚 憲生

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