PUBLICATION
The direct impact of pegvisomant on osteoblast functions and bone development
- Authors
- Vitali, E., Grasso, A., Schiavone, M.L., Trivellin, G., Sobacchi, C., Mione, M., Mazziotti, G., Lania, A.
- ID
- ZDB-PUB-240103-9
- Date
- 2023
- Source
- Journal of endocrinological investigation 47(6): 1385-1394 (Journal)
- Registered Authors
- Mione, Marina
- Keywords
- Acromegaly, Growth hormone, Osteoblast, Pegvisomant, Zebrafish
- MeSH Terms
-
- Animals
- Apoptosis/drug effects
- Bone Development*/drug effects
- Cell Differentiation*/drug effects
- Cell Proliferation*/drug effects
- Human Growth Hormone*/analogs & derivatives
- Human Growth Hormone*/pharmacology
- Humans
- Insulin-Like Growth Factor I/metabolism
- Mice
- Osteoblasts*/drug effects
- Osteoblasts*/metabolism
- Zebrafish*
- PubMed
- 38159174 Full text @ J. Endocrinol. Invest.
Citation
Vitali, E., Grasso, A., Schiavone, M.L., Trivellin, G., Sobacchi, C., Mione, M., Mazziotti, G., Lania, A. (2023) The direct impact of pegvisomant on osteoblast functions and bone development. Journal of endocrinological investigation. 47(6):1385-1394.
Abstract
Purpose Acromegaly is a chronic disease characterized by growth hormone (GH) hypersecretion, usually caused by a pituitary adenoma, resulting in elevated circulating levels of insulin-like growth factor type I (IGF-I). Pegvisomant (PEG), the GH-receptor (GHR) antagonist, is used in treating acromegaly to normalize IGF-I hypersecretion. Exposure to increased levels of GH and IGF-I can cause profound alterations in bone structure that are not completely reverted by treatment of GH hypersecretion. Indeed, there is evidence that drugs used for the treatment of acromegaly might induce direct effects on skeletal health regardless of biochemical control of acromegaly.
Methods We investigated, for the first time, the effect of PEG on cell proliferation, differentiation, and mineralization in the osteoblast cell lines MC3T3-E1 and hFOB 1.19 and its potential impact on bone development in zebrafish larvae.
Results We observed that PEG did not affect osteoblast proliferation, apoptosis, alkaline phosphatase (ALP) activity, and mineralization. After PEG treatment, the analysis of genes related to osteoblast differentiation showed no difference in Alp, Runx2, or Opg mRNA levels in MC3T3-E1 cells. GH significantly decreased cell apoptosis (- 30 ± 11%, p < 0.001) and increased STAT3 phosphorylation; these effects were suppressed by the addition of PEG in MC3T3-E1 cells. GH and PEG did not affect Igf-I, Igfbp2, and Igfbp4 mRNA levels in MC3T3-E1 cells. Finally, PEG did not affect bone development in zebrafish larvae at 5 days post-fertilization.
Conclusion This study provides a first evidence of the impact of PEG on osteoblast functions both in vitro and in vivo. These findings may have clinically relevant implications for the management of skeletal health in subjects with acromegaly.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping