International journal of molecular sciences, 2021-10, Vol.22 (20), p.11265
2021
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- Autor(en) / Beteiligte
- Titel
- Toxic Effects of Indoxyl Sulfate on Osteoclastogenesis and Osteoblastogenesis
- Ist Teil von
- International journal of molecular sciences, 2021-10, Vol.22 (20), p.11265
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2021
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Uremic toxins, such as indoxyl sulfate (IS) and kynurenine, accumulate in the blood in the event of kidney failure and contribute to further bone damage. To maintain the homeostasis of the skeletal system, bone remodeling is a persistent process of bone formation and bone resorption that depends on a dynamic balance of osteoblasts and osteoclasts. The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates the toxic effects of uremic toxins. IS is an endogenous AhR ligand and is metabolized from tryptophan. In osteoclastogenesis, IS affects the expression of the osteoclast precursor nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) through AhR signaling. It is possible to increase osteoclast differentiation with short-term and low-dose IS exposure and to decrease differentiation with long-term and/or high-dose IS exposure. Coincidentally, during osteoblastogenesis, through the AhR signaling pathway, IS inhibits the phosphorylation of ERK, and p38 reduces the expression of the transcription factor 2 (Runx2), disturbing osteoblastogenesis. The AhR antagonist resveratrol has a protective effect on the IS/AhR pathway. Therefore, it is necessary to understand the multifaceted role of AhR in CKD, as knowledge of these transcription signals could provide a safe and effective method to prevent and treat CKD mineral bone disease.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms222011265Titel-ID: cdi_doaj_primary_oai_doaj_org_article_631323d601b54557868ed1acc0c02376
- Format
- –
- Schlagworte
- Aluminum, Animals, aryl hydrocarbon receptor, Basic Helix-Loop-Helix Transcription Factors - metabolism, Biomedical materials, Bone diseases, Bone growth, Bone remodeling, Bone resorption, Calcification, Cbfa-1 protein, Cell Differentiation - drug effects, Differentiation, Fractures, Gene expression, Gene Expression Regulation - drug effects, Homeostasis, Humans, Indican - toxicity, Indican - urine, indoxyl sulfate, Ligands, Lymphocytes, Metabolism, Metabolites, Mineralization, Mortality, NF-AT protein, NFATC Transcription Factors - metabolism, osteoblast, Osteoblastogenesis, Osteoblasts - cytology, Osteoblasts - drug effects, Osteoblasts - metabolism, osteoclast, Osteoclastogenesis, Osteoclasts, Osteoclasts - cytology, Osteoclasts - drug effects, Osteoclasts - metabolism, Osteogenesis, Osteogenesis - drug effects, Oxidative stress, Phosphorylation, Receptors, Aryl Hydrocarbon - metabolism, Renal failure, Renal Insufficiency, Chronic - complications, Renal Insufficiency, Chronic - metabolism, Renal Insufficiency, Chronic - urine, Resveratrol, Review, Signal transduction, Signal Transduction - drug effects, Signaling, Toxins, Transcription factors, Tryptophan