ArticleAnnals of the rheumatic diseases2010
Synergistic induction of local glucocorticoid generation by inflammatory cytokines and glucocorticoids: implications for inflammation associated bone loss.
Article in Annals of the rheumatic diseases, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
31 citing papers in PubMed, 66 citations in OpenAlex.
- 11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial.Nature communications · 2023Trial
- Glucocorticoids in breast cancer: physiologic mechanisms and relationship to risk, survival, and treatment response.Frontiers in endocrinology · 2026Review
- The Glucocorticoid Receptor: Isoforms, Functions, and Contribution to Glucocorticoid Sensitivity.Endocrine reviews · 2024Review
- Musculoskeletal complications of Cushing syndrome.Reumatologia · 2023Review
- 11β-Hydroxysteroid Dehydrogenase Type 1 Facilitates Osteoporosis by Turning on Osteoclastogenesis through Hippo Signaling.International journal of biological sciences · 2023Article
- Dexamethasone-loaded zeolitic imidazolate frameworks nanocomposite hydrogel with antibacterial and anti-inflammatory effects for periodontitis treatment.Materials today. Bio · 2022Article
- 11β-Hydroxysteroid Dehydrogenase Type 1 within Osteoclasts Mediates the Bone Protective Properties of Therapeutic Corticosteroids in Chronic Inflammation.International journal of molecular sciences · 2022Article
- Sex Steroid Regulation of Oxidative Stress in Bone Cells: An In Vitro Study.International journal of environmental research and public health · 2021Article
- [Safety aspects of the treatment with glucocorticoids for rheumatoid arthritis].Zeitschrift fur Rheumatologie · 2021Review
- Endogenous Glucocorticoid Metabolism in Bone: Friend or Foe.Frontiers in endocrinology · 2021Review
- HSD11B1 is upregulated synergistically by IFNγ and TNFα and mediates TSG-6 expression in human UC-MSCs.Cell death discovery · 2020Article
- Cortisol Regeneration in the Fetal Membranes, A Coincidental or Requisite Event in Human Parturition?Frontiers in physiology · 2020Review
- Exploring the Interface between Inflammatory and Therapeutic Glucocorticoid Induced Bone and Muscle Loss.International journal of molecular sciences · 2019Review
- 11β-HSD1 plays a critical role in trabecular bone loss associated with systemic glucocorticoid therapy.Arthritis research & therapy · 2019Article
- Adrenal Steroids Modulate Fibroblast-Like Synoviocytes Response DuringFrontiers in endocrinology · 2019Article
- 11 Beta-hydroxysteroid dehydrogenase type 1 regulates synovitis, joint destruction, and systemic bone loss in chronic polyarthritis.Journal of autoimmunity · 2018Article
- 11β-hydroxysteroid dehydrogenases as targets in the treatment of steroid-associated femoral head necrosis using antler extract.Experimental and therapeutic medicine · 2018Article
- Getting to the heart of intracellular glucocorticoid regeneration: 11β-HSD1 in the myocardium.Journal of molecular endocrinology · 2017Review
- 11β-Hydroxysteroid dehydrogenase type 1 within muscle protects against the adverse effects of local inflammation.The Journal of pathology · 2016Article
- A novel role for the mineralocorticoid receptor in glucocorticoid driven vascular calcification.Vascular pharmacology · 2016Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
objectivesSynovial fibroblasts and osteoblasts generate active glucocorticoids by means of the 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) enzyme. This activity increases in response to proinflammatory cytokines or glucocorticoids. During inflammatory arthritis synovium and bone are exposed to both these factors. This study hypothesised that glucocorticoids magnify the effects of inflammatory cytokines on local glucocorticoid production in both synovium and bone.
methodsThe effects of inflammatory cytokines (IL-1beta/tumour necrosis factor alpha; TNFalpha) and glucocorticoids, alone or combined, were assessed on the expression and activity of 11beta-HSD1 in primary synovial fibroblasts, primary human osteoblasts and MG-63 osteosarcoma cells. A range of other target genes and cell types were used to examine the specificity of effects. Functional consequences were assessed using IL-6 ELISA.
resultsIn synovial fibroblasts and osteoblasts, treatment with cytokines or glucocorticoids in isolation induced 11beta-HSD1 expression and activity. However, in combination, 11beta-HSD1 expression, activity and functional consequences were induced synergistically to a level not seen with isolated treatments. This effect was seen in normal skin fibroblasts but not foreskin fibroblasts or adipocytes and was only seen for the 11beta-HSD1 gene. Synergistic induction had functional consequences on IL-6 production.
conclusionsCombined treatment with inflammatory cytokines and glucocorticoids synergistically induces 11beta-HSD1 expression and activity in synovial fibroblasts and osteoblasts, providing a mechanism by which synovium and bone can interact to enhance anti-inflammatory responses by increasing localised glucocorticoid levels. However, the synergistic induction of 11beta-HSD1 might also cause detrimental glucocorticoid accumulation in bone or surrounding tissues.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.