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Cited by 10Bone Metabolism and DiseasesBone health and treatmentsBone health and osteoporosis research

Effect of nitrogen-containing bisphosphonates on osteoclasts and osteoclastogenesis: an ultrastructural study

Takagi, Yoshitoki, Inoue, Satoshi, Fujikawa, Kaoru, Matsuki-Fukushima, Miwako, Mayahara, Mitsuori, Matsuyama, Kayo, Endo, Yasuo, Nakamura, Masanori·2021·Microscopy
DOI 10.1093/jmicro/dfaa073
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Abstract

We have previously indicated that a single injection of alendronate, one of the nitrogen-containing bisphosphonates (NBPs), affects murine hematopoietic processes, such as the shift of erythropoiesis from bone marrow (BM) to spleen, disappearance of BM-resident macrophages, the increase of granulopoiesis in BM and an increase in the number of osteoclasts. NBPs induce apoptosis and the formation of giant osteoclasts in vitro and/or in patients undergoing long-term NBP treatment. Therefore, the time-kinetic effect of NBPs on osteoclasts needs to be clarified. In this study, we examined the effect of alendronate on mouse osteoclasts and osteoclastogenesis. One day after the treatment, osteoclasts lost the clear zone and ruffled borders, and the cell size decreased. After 2 days, the cytoplasm of osteoclasts became electron dense and the nuclei became pyknotic. Some of the cells had fragmented nuclei. After 4 days, osteoclasts had euchromatic nuclei attached to the bone surface. Osteoclasts had no clear zones or ruffled borders. After 7 days, osteoclasts formed giant osteoclasts via the fusion of multinuclear and mononuclear osteoclasts. These results indicate that NBPs affect osteoclasts and osteoclastogenesis via two different mechanisms.

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Crossref · 10.1093/jmicro/dfaa073

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  • NBPs first induce osteoclast apoptosis and then formation of newly differentiated osteoclasts that can anchor the bone surface but cannot form a clear zone or ruffled border.

    “A recent study with transmission electron microscopy demonstrated that NBPs first induce osteoclast apoptosis and then the formation of newly differentiated osteoclasts that can anchor the bone surface but cannot form a clear zone or ruffled border.157”

    From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [157]

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Authors
Takagi, Y., Inoue, S., Fujikawa, K., Matsuki-Fukushima, M., Mayahara, M., Matsuyama, K., Endo, Y., & Nakamura, M.
Affiliations
  • SHOWA Medical University (JP)
  • Tohoku University (JP)
Corresponding author
Nakamura, Masanori
ORCID
Venue
Microscopy
Publisher
Oxford University Press (OUP)
Published
2020-12-04
Volume
70
Issue
3
Pages
302-307
ISSN
  • 2050-5698 (ISSN-L)
  • 2050-5701
DOI
10.1093/jmicro/dfaa073
OpenAlex
W3107856623
Cited by
10
References
39
Citations by year
2026: 1 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 1
FWCI
0.49
Type
journal article
Language
en
Open access
closed
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Microscopy (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministry of Education, Culture, Sports, Science and Technology of Japan (24592777, 15K11022 and 20K18516)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
  • Health Sciences › Medicine › Oncology › Bone health and treatments
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords
nitrogen-containing bisphosphonates, alendronate, osteoclasts, osteoclastogenesis, osteoclast ultrastructure, ruffled border, clear zone, osteoclast apoptosis, osteoclast fusion, bone resorption, bone marrow-derived macrophages
MeSH terms
Animals, Bone and Bones, Diphosphonates, Erythropoiesis, Male, Mice, Inbred BALB C, Nitrogen, Osteoclasts, Osteogenesis, Apoptosis, Alendronate, Microscopy, Electron, Transmission, Bone Density Conservation Agents, Mice

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