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Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin
Open accessAbstract
Glucocorticoid-induced osteoporosis may be due, in part, to increased apoptosis of osteocytes and osteoblasts, and bisphosphonates (BPs) are effective in the management of this condition. We have tested the hypothesis that BPs suppress apoptosis in these cell types. Etidronate, alendronate, pamidronate, olpadronate, or amino-olpadronate (IG9402, a bisphosphonate that lacks antiresorptive activity) at 10(-9) to 10(-6) M prevented apoptosis of murine osteocytic MLO-Y4 cells, whether it was induced by etoposide, TNF-alpha, or the synthetic glucocorticoid dexamethasone. BPs also inhibited apoptosis of primary murine osteoblastic cells isolated from calvaria. Similar antiapoptotic effects on MLO-Y4 and osteoblastic cells were seen with nanomolar concentrations of the peptide hormone calcitonin. The antiapoptotic effect of BPs and calcitonin was associated with a rapid increase in the phosphorylated fraction of extracellular signal regulated kinases (ERKs) and was blocked by specific inhibitors of ERK activation. Consistent with these in vitro results, alendronate abolished the increased prevalence of apoptosis in vertebral cancellous bone osteocytes and osteoblasts that follows prednisolone administration to mice. These results suggest that the therapeutic efficacy of BPs or calcitonin in diseases such as glucocorticoid-induced osteoporosis may be due, in part, to their ability to prevent osteocyte and osteoblast apoptosis.
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“Induction of apoptosis in MLO/Y4 cells by etoposide, TNF-␣, or glucocorticoids was prevented by pretreatment of the cells with 5-10 ng/mL sCT.”
From The Activity of Peptides of the Calcitonin Family in Bone (2019) · cites this paper as [167]
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“The authors suggest that the therapeutic effect of calcitonin in diseases such as glucocorticoid-induced osteoporosis may be partly due to inhibition of osteocyte apoptosis (167).”
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Self-citation
Metadata
- Authors
- Plotkin, L. I., Weinstein, R. S., Parfitt, A. M., Roberson, P. K., Manolagas, S. C., & Bellido, T.
- Affiliations
- University of Arkansas for Medical Sciences (US)
- Central Arkansas Veterans Healthcare System (US)
- Corresponding author
- Bellido, Teresita
- Venue
- Journal of Clinical Investigation
- Published
- 1999-11-15
- Volume
- 104
- Issue
- 10
- Pages
- 1363-1374
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC409837
- OpenAlex
- W2170680219
- Cited by
- 890
- References
- 62
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 11 · 2023: 13 · 2022: 19 · 2021: 15 · 2020: 21 · 2019: 24 · 2018: 24 · 2017: 29 · 2016: 41 · 2015: 26 · 2014: 54 · 2013: 44 · 2012: 40
- FWCI
- 11.43
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ar043003-05)
- National Institute on Aging (P01AG/AMS13918, P01AG013918)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01 AR43003, R01AR046191)
- 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
- bisphosphonates, calcitonin, osteocyte apoptosis, osteoblast apoptosis, glucocorticoid-induced osteoporosis, alendronate, etidronate, pamidronate, extracellular signal-regulated kinase, ERK1/2 phosphorylation, dexamethasone, TNF-α, etoposide, prednisolone, MLO-Y4 cells, trabecular bone
- MeSH terms
- Pamidronate, Animals, Calcitonin, Cell Line, Cells, Cultured, Dexamethasone, Diphosphonates, Etoposide, Osteoblasts, Osteocytes, Prednisolone, Skull, Etidronic Acid, Tumor Necrosis Factor-alpha, Apoptosis, Alendronate, In Situ Nick-End Labeling, Mice
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