Journal
MICROSCOPY
Volume 70, Issue 3, Pages 302-307Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jmicro/dfaa073
Keywords
alendronate; bisphosphonate; nitrogen-containing bisphosphonate; osteoclast; osteoclastogenesis; transmission; electron microscopy
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [24592777, 15K11022, 20K18516]
- Grants-in-Aid for Scientific Research [15K11022, 20K18516, 24592777] Funding Source: KAKEN
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The study found that alendronate affects mouse osteoclasts by altering cell structure and inducing fusion of osteoclasts to form giant cells.
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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