Histochemical evidence of zoledronate inhibiting c-src expression and interfering with CD44/OPN-mediated osteoclast adhesion in the tibiae of mice
Abstract
The purpose of this study was to investigate the effect of zoledronate (ZA) on osteoclast functions and viability in the tibiae of 8-week-old male mice. After weekly intravenous administration of ZA (125 μg/kg body weight) for 8 weeks, the mice were fixed by transcardial perfusion of 4% paraformaldehyde under anesthesia, and their tibiae were extracted for histochemical analysis. Compared with the control group, many tartrate-resistant acidic phosphatase-positive osteoclasts were found on the surface of the trabecular bone, but cartilage cores were obviously increased in the metaphysis of the ZA group. Osteoclasts of both groups showed similar expression of cathepsin K and matrix metalloproteinase-9. However, hardly any expression of c-src, a gene necessary for ruffled border formation and bone resorption, was found in osteoclasts of the ZA group. Moreover, no expression of CD44 or osteopontin (OPN) was observed in osteoclasts of the ZA group. Taken together, our findings suggest that ZA administration decreases the bone resorption ability of osteoclasts by inhibiting c-src expression and suppressing osteoclast adhesion by interfering with CD44/OPN binding.
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NBPs induce osteoclasts to acquire a nonresorbing phenotype by inhibiting c-Src and stimulating DC-STAMP.
“NPBs induce osteoclasts to acquire a nonresorbing phenotype by inhibiting c-Src, which is essential for cytoskeletal construction,158 and by stimulating dendritic cell-specific transmembrane protein (DC-STAMP),159 which is necessary for cell fusion.”
From Bone remodeling: an operational process ensuring survival and bone mechanical competence (2022) · cites this paper as [158]
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Bone remodeling: an operational process ensuring survival and bone mechanical competence
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- Authors
- Liu, H., Cui, J., Sun, J., Du, J., Feng, W., Sun, B., Li, J., Han, X., Liu, B., Yimin, Oda, K., Amizuka, N., & Li, M.
- Affiliations
- Shandong University (CN)
- Hokkaido University (JP)
- Niigata University (JP)
- Corresponding author
- Li, Minqi
- Venue
- Journal of Molecular Histology
- Published
- 2015-05-13
- Volume
- 46
- Issue
- 3
- Pages
- 313-323
- ISSN
- 1567-2379 (ISSN-L)
- 1567-2387
- OpenAlex
- W778301592
- Cited by
- 11
- References
- 44
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2020: 1 · 2017: 2 · 2016: 2
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Journal of Molecular Histology (publishedVersion)
- PubMed (publishedVersion)
- 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
- zoledronic acid, osteoclasts, Src kinase, CD44, osteopontin, osteoclast adhesion, bone resorption, cathepsin K, MMP-9, ruffled border, trabecular bone, tibia, bisphosphonates
- MeSH terms
- Zoledronic Acid, CSK Tyrosine-Protein Kinase, Animals, Cell Adhesion, Diphosphonates, Drug Evaluation, Preclinical, Imidazoles, Male, Osteoblasts, Osteoclasts, Tibia, Gene Expression, Hyaluronan Receptors, src-Family Kinases, Bone Density Conservation Agents, Mice, Osteopontin
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