ArticleBone2007
Cyclosporin A elicits dose-dependent biphasic effects on osteoblast differentiation and bone formation.
Article in Bone, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
45 citing papers in PubMed, 96 citations in OpenAlex.
- Myricitrin: A promising herbal therapy for periodontitis in immunosuppressed status.The Saudi dental journal · 2023Article
- The role of CaCell proliferation · 2021Review
- FK506 ameliorates osteoporosis caused by osteoblast apoptosis via suppressing the activated CaN/NFAT pathway during oxidative stress.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Article
- PERK signaling pathway in bone metabolism: Friend or foe?Cell proliferation · 2021Review
- Cyclosporine A Promotes Bone Remodeling in LPS-Related Inflammation via Inhibiting ROS/ERK Signaling: StudiesOxidative medicine and cellular longevity · 2021Article
- A review of the latest insights into the mechanism of action of strontium in bone.Bone reports · 2020Review
- Drug-metabolizing enzymes CYP3A as a link between tacrolimus and vitamin D in renal transplant recipients: is it relevant in clinical practice?Pediatric nephrology (Berlin, Germany) · 2019Review
- Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Tissue-Nonspecific Alkaline Phosphatase Is Required for MC3T3 Osteoblast-Mediated Protection of Acute Myeloid Leukemia Cells from Apoptosis.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Identification of potential pathogenic genes associated with osteoporosis.Bone & joint research · 2017Article
- CYP3A4 is a crosslink between vitamin D and calcineurin inhibitors in solid organ transplant recipients: implications for bone health.The pharmacogenomics journal · 2017Review
- RCANs regulate the convergent roles of NFATc1 in bone homeostasis.Scientific reports · 2016Article
- Cyclophilin A (CypA) Plays Dual Roles in Regulation of Bone Anabolism and Resorption.Scientific reports · 2016Article
- Mineral and bone disorders in kidney transplant recipients: reversible, irreversible, and de novo abnormalities.Clinical and experimental nephrology · 2015Review
- Activation of Nfatc2 in osteoblasts causes osteopenia.Journal of cellular physiology · 2015Article
- The calcineurin-NFAT axis controls allograft immunity in myeloid-derived suppressor cells through reprogramming T cell differentiation.Molecular and cellular biology · 2015Article
- The Effect of SERCA1b Silencing on the Differentiation and Calcium Homeostasis of C2C12 Skeletal Muscle Cells.PloS one · 2015Article
- Cyclosporin A induces cardiac differentiation but inhibits hemato-endothelial differentiation of P19 cells.PloS one · 2015Article
- Current Status of Research on Osteoporosis after Solid Organ Transplantation: Pathogenesis and Management.BioMed research international · 2015Review
- Enhancement of Flow-Induced AP-1 Gene Expression by Cyclosporin A Requires NFAT-Independent Signaling in Bone Cells.Cellular and molecular bioengineering · 2014Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cyclosporin A (CsA) is thought to prevent immune reactions after organ transplantation by inhibiting calcineurin (Cn) and its substrate, the Nuclear Factor of Activated T Cells (NFAT). A dichotomy exists in describing the effects of CsA on bone formation. The concept that the suppression of Cn/NFAT signaling by CsA inhibits bone formation is not entirely supported by many clinical reports and laboratory animal studies. Gender, dosage and basal inflammatory activity have all been suggested as explanations for these seemingly contradictory reports. Here we examine the effects of varying concentrations of CsA on bone formation and osteoblast differentiation and elucidate the role of NFATc1 in this response. We show that low concentrations of CsA (<1 microM in vitro and 35.5 nM in vivo) are anabolic as they increase bone formation, osteoblast differentiation, and bone mass, while high concentrations (>1 microM in vitro and in vivo) elicit an opposite and catabolic response. The overexpression of constitutively active NFATc1 inhibits osteoblast differentiation, and treatment with low concentrations of CsA does not ameliorate this inhibition. Treating osteoblasts with low concentrations of CsA (<1 microM) increases fra-2 gene expression and protein levels in a dose-dependent manner as well as AP-1 DNA-binding activity. Finally, NFATc1 silencing with siRNA increases Fra-2 expression, whereas NFATc1 overexpression inhibits Fra-2 expression. Therefore, NFATc1 negatively regulates osteoblast differentiation, and its specific inhibition may represent a viable anabolic therapy for osteoporosis.
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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.