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c-Fos induction by gut hormones and extracellular ATP in osteoblastic-like cell lines
Open accessAbstract
It is widely accepted that the c-Fos gene has a role in proliferation and differentiation of bone cells. ATP-induced c-Fos activation is relevant to bone homeostasis, because nucleotides that are present in the environment of bone cells can contribute to autocrine/paracrine signalling. Gut hormones have previously been shown to have an effect on bone metabolism. In this study, we used the osteoblastic Saos-2 cell line transfected with a c-Fos-driven reporter stimulated with five gut hormones: glucose inhibitory peptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2), ghrelin and obestatin, in the presence or absence of ATP. In addition, TE-85 cells were used to determine the time course of c-Fos transcript induction following stimulation with GLP-1, and GLP-2 with or without ATP, using reverse transcription qPCR. The significant results from the experiments are as follows: higher level of c-Fos induction in presence of GIP, obestatin (p = 0.019 and p = 0.011 respectively), and GIP combined with ATP (p < 0.001) using the luciferase assay; GLP-1 and GLP-2 combined with ATP (p = 0.034 and p = 0.002, respectively) and GLP-2 alone (p < 0.001) using qPCR. In conclusion, three of the gut peptides induced c-Fos, providing a potential mechanism underlying the actions of these hormones in bone which can be directed or enhanced by the presence of ATP.
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In vitro, GLP-1 disrupts ability of osteoblasts to survive and differentiate by triggering activation of c-Fos.
“In vitro, GLP-1 disrupts the ability of osteoblasts to survive and differentiate by triggering the activation of c-Fos, which is a proto-oncogene.373”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [373]
The RT-qPCR Results (page not provided) report increased c-Fos expression in TE-85 osteoblastic cells when GLP-1 was combined with ATP. The paper does not report that GLP-1 disrupts osteoblast survival or differentiation, nor does it establish c-Fos induction as a cause of either effect. (LLM, conf=0.90)
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Glucagon-like peptide-1 receptor: mechanisms and advances in therapy
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“373 In fact, when BMSCs are exposed to exendin-4, the expression of genes related to bone development factors such as Runx and Osterix, as well as genes responsible for producing the bone matrix such as Balp and Bglap, is upregulated.”
BackgroundTargeting the GLP-1/GLP-1R axis to treat osteoarthritis: A new opportunity?
Meurot, C., Jacques, C., Martin, C., Sudre, L., Breton, J., Rattenbach, R., Bismuth, K., & Berenbaum, F. (2022) · Journal of Orthopaedic Translation · doi:10.1016/j.jot.2022.02.001 · Cited by 94
Metadata
- Authors
- Pacheco-Pantoja, E. L., Dillon, J. P., Wilson, P. J. M., Fraser, W. D., & Gallagher, J. A.
- Affiliations
- Anahuac Mayab University (MX)
- University of East Anglia (GB)
- Corresponding author
- Pacheco-Pantoja, Elda Leonor
- Venue
- Purinergic Signalling
- Published
- 2016-07-20
- Volume
- 12
- Issue
- 4
- Pages
- 647-651
- ISSN
- 1573-9538 (ISSN-L)
- 1573-9546
- PMC
- PMC5124003
- OpenAlex
- W2505072971
- Cited by
- 21
- References
- 34
- Citations by year
- 2025: 5 · 2024: 4 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 1 · 2017: 1
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Purinergic Signalling (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UEA Digital Repository (University of East Anglia) (acceptedVersion)
- Funders
- Consejo Nacional de Ciencia y Tecnología (206349)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- c-fos, gastrointestinal hormones, extracellular ATP, osteoblasts, glucagon-like peptide-1, glucagon-like peptide-2, ghrelin, obestatin, bone metabolism, autocrine and paracrine signaling, Saos-2 cells
- MeSH terms
- Adenosine Triphosphate, Humans, Osteoblasts, Proto-Oncogene Proteins c-fos, Cell Line, Tumor, Glucagon-Like Peptide 1, Glucagon-Like Peptide 2, Ghrelin
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