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Localization of Minodronate in Mouse Femora Through Isotope Microscopy
- Source :
- Journal of Histochemistry & Cytochemistry. 64(10):601-622
- Publication Year :
- 2016
- Publisher :
- SAGE Publications, 2016.
-
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 transmission electron microscopy (TEM). Eight-week-old male ICR mice received [15N]-minodronate (1 mg/kg) intravenously and were sacrificed after 3 hr, 24 hr, 1 week, and 1 month. Isotope microscopy showed that [15N]-minodronate was present mainly beneath osteoblasts rather than nearby osteoclasts. At 3 hr 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 hr after minodronate administration. The numbers of tartrate-resistant acid phosphatase–positive osteoclasts and alkaline phosphatase–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.
- Subjects :
- 0301 basic medicine
musculoskeletal diseases
Male
medicine.medical_specialty
bisphosphonate
Histology
medicine.medical_treatment
Osteoclasts
030209 endocrinology & metabolism
Cell Count
03 medical and health sciences
0302 clinical medicine
Osteoclast
Internal medicine
medicine
Animals
minodronate
Femur
Von Kossa stain
Carbon Isotopes
Mice, Inbred ICR
Microscopy
Osteoblasts
Bone Density Conservation Agents
Diphosphonates
Nitrogen Isotopes
Chemistry
Imidazoles
Osteoblast
Anatomy
Articles
Bisphosphonate
isotope microscopy
Staining
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Apoptosis
osteoclast
osteoblast
Subjects
Details
- Language :
- English
- ISSN :
- 00221554
- Volume :
- 64
- Issue :
- 10
- Database :
- OpenAIRE
- Journal :
- Journal of Histochemistry & Cytochemistry
- Accession number :
- edsair.doi.dedup.....298ce7e661345d8909c0a56b493cb815