Abstract
Purpose
Gorham-Stout disease is a very rare disorder characterized by progressive bone erosion and angiomatous proliferation; its etiopathogenesis is still unknown, and diagnosis is still performed by exclusion criteria. The alteration of bone remodeling activity has been reported in patients; in this study, we characterized circulating osteoclast and osteogenic precursors that could be important to better understand the osteolysis observed in patients.
Methods
Flow cytometry analysis of PBMC (Peripheral Blood Mononuclear Cells) was performed to characterize circulating osteoclast and osteogenic precursors in GSD patients (n = 9) compared to healthy donors (n = 55). Moreover, ELISA assays were assessed to evaluate serum levels of bone markers including RANK-L (Receptor activator of NF-κB ligand), OPG (Osteoprotegerin), BALP (Bone Alkaline Phosphatase) and OCN (Osteocalcin).
Results
We found an increase of CD16−/CD14+CD11b+ and CD115+/CD14+CD11b+ osteoclast precursors in GSD patients, with high levels of serum RANK-L that could reflect the increase of bone resorption activity observed in patients. Moreover, no significant alterations were found regarding osteogenic precursors and serum levels of BALP and OCN.
Conclusion
The analysis of circulating bone cell precursors, as well as of RANK-L, could be relevant as an additional diagnostic tool for these patients and could be exploited for therapeutic purposes.
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Acknowledgements
This work was supported by research grants (#MDBR-19-116-LGDA/LMI and #MDBR-21-111-LGDA/LMI) from the University of Pennsylvania Orphan Disease Center in partnership with Lymphangiomatosis & Gorham’s Disease Alliance and the Lymphatic Malformation Institute to ADF, by the Ricerca Finalizzata Ministero della Salute (GR-2019-12370244) to ADF, and by the Italian Ministry of Health (Current Research funds). MR, ST and JDG were supported by Fondazione Umberto Veronesi.
Funding
This work was supported by research grants (#MDBR-19-116-LGDA/LMI and #MDBR-21-111-LGDA/LMI) from the University of Pennsylvania Orphan Disease Center in partnership with Lymphangiomatosis & Gorham’s Disease Alliance and the Lymphatic Malformation Institute to ADF, by the Ricerca Finalizzata Ministero della Salute (GR-2019-12370244) to ADF, and by the Italian Ministry of Health (Current Research funds). MR, ST and JDG were supported by Fondazione Umberto Veronesi.
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MR, ST, GB, LDG, MDA, OP and JDG performed analysis of bone cells precursors and contributed to the discussion of the results. IR, PSB, MVG, CC and AJ recruited the patients and performed the ELISA assays. ADF and AB designed and supervised the work and wrote the paper. All authors reviewed the manuscript and approved the final version. ADF is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.
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All the procedures performed in this study involving human participants were in accordance with the ethical standards as laid down in the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Both patients and parents were required to sign the informed consent form to participate in the study.
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The study was approved by Bambino Gesù Children’s Hospital's ethics committee (Protocol No. GR-2019-12370244, 01/02/2021).
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40618_2024_2365_MOESM1_ESM.tif
Supplementary file1 FACS negative staining controls. A Representative FACS plots of Fluorescence Minus One (FMO) control for A CD115-BV605 and B CD34-BV650 staining. Left panels: FMO control; right panels: fully stained (TIF 1208 KB)
40618_2024_2365_MOESM2_ESM.tif
Supplementary file2 Correlations of serum markers with osteoclast precursor populations. A Correlations of RANK-L and CD16− (left panel) or CD16+ (right panel) cell percentage in the gate of CD14+CD11b+ cells. B Correlation of OPG and CD115+ cell percentage in the gate of CD14+CD11b+ cells. The p values are obtained from linear regression analysis (TIF 904 KB)
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Rossi, M., Terreri, S., Battafarano, G. et al. Analysis of circulating osteoclast and osteogenic precursors in patients with Gorham-Stout disease. J Endocrinol Invest (2024). https://doi.org/10.1007/s40618-024-02365-8
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DOI: https://doi.org/10.1007/s40618-024-02365-8