Imbalance of osteoclastogenesis-regulating factors in patients with celiac disease.
Open accessAbstract
Celiac disease is an autoimmune disorder characterized by atrophy of the intestine villi triggered by ingestion of gluten in genetically susceptible individuals. The association between celiac disease and low BMD has been recognized, but the mechanisms of disturbance are poorly understood. We show imbalance of cytokines relevant to bone metabolism in celiac patients' sera and the direct effect of these sera on in vitro bone cell activity. Introduction: Celiac disease is associated with mineral metabolism derangement and low BMD. We investigated whether imbalance of serum factors in celiac patients could affect human bone cell activity in vitro. Materials and Methods: We studied two groups of celiac patients—one on a gluten-free diet and another before the diet—both with decreased bone mass. Patients were investigated for bone turnover markers, and their sera were used for culturing bone cells from healthy donors and evaluate changes in cell activity. Results: The N-terminal telopeptide of procollagen type I and interleukin (IL)-6 were higher than normal in patients not on the gluten-free diet. IL-1β and TNF-α/β were normal in all patients. IL-12 was reduced in all patients, whereas IL-18 was reduced only in patients on the diet. The RANKL/Osteoprotegerin (OPG) ratio was increased in patients not on the gluten-free diet. Persistently increased osteoclast numbers were obtained from peripheral blood mononuclear cells of healthy donors on incubation with sera of patients not on the gluten-free diet versus control sera and sera from patients on the diet. In human osteoblasts from healthy individuals, IL-18 was reduced on incubation with sera from all patients, whereas OPG expression was lower when sera from patients not on the diet were used. Proliferation, alkaline phosphatase, and nodule mineralization were increased in osteoblast cultures containing sera from all celiac patients, either on or not on the gluten-free diet. Conclusions: We conclude that bone loss in celiac disease might also be caused by a cytokine imbalance directly affecting osteoclastogenesis and osteoblast activity.
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Osteoclast activity likely depends at least in part on the relative balance between RANKL and OPG.
“Osteoclast activity is likely to depend, at least in part, on the relative balance of RANKL and OPG.”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [94]
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References 38 · Cited by 118
- Authors
- Taranta, A., Fortunati, D., Longo, M., Rucci, N., Iacomino, E., Aliberti, F., Facciuto, E., Migliaccio, S., Bardella, M. T., Dubini, A., Borghi, M. O., Saraifoger, S., Teti, A., & Bianchi, M. L.
- Affiliations
- Istituto Dermopatico dell'Immacolata (IT)
- Sapienza University of Rome (IT)
- University of L'Aquila (IT)
- Santobono Children's Hospital (IT)
- Ospedale Antonio Cardarelli (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- IRCCS Istituto Auxologico Italiano (IT)
- Bone Metabolic Unit, Istituto Auxologico Italiano, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
- Corresponding author
- Teti, Anna
- Venue
- Journal of Bone and Mineral Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-07-01
- Volume
- 19
- Issue
- 7
- Pages
- 1112-1121
- ISSN
- 0884-0431 (ISSN-L)
- 1523-4681
- OpenAlex
- W1972880322
- Cited by
- 118
- References
- 38
- Citations by year
- 2025: 3 · 2024: 8 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 8 · 2012: 7
- FWCI
- 5.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- Journal of Bone and Mineral Research (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- Funders
- Ministero della Salute
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Agenzia Spaziale Italiana
- Associazione Italiana per la Ricerca sul Cancro
- Topics
- Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- celiac disease, osteoclastogenesis, osteoblast activity, bone loss, osteopenia, cytokine imbalance, IL-18, interleukin-6, osteoprotegerin, osteoclasts, bone turnover markers, gluten-free diet, bone metabolism, mineral metabolism
- MeSH terms
- Adult, Alkaline Phosphatase, Bone Resorption, Carrier Proteins, Celiac Disease, Collagen, Female, Glutens, Glycoproteins, Humans, Leukocytes, Mononuclear, Male, Membrane Glycoproteins, Osteoblasts, Osteoclasts, Peptides, Biomarkers, Bone Density, Cytokines, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Collagen Type I, Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating), Parathyroid Hormone-Related Protein, Osteoprotegerin, RANK Ligand, Receptor Activator of Nuclear Factor-kappa B
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