{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:08:14Z","timestamp":1792382894923,"version":"4.4.0"},"reference-count":129,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2021,10,19]],"date-time":"2021-10-19T00:00:00Z","timestamp":1634601600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008904","name":"Taipei Hospital","doi-asserted-by":"publisher","award":["202104"],"award-info":[{"award-number":["202104"]}],"id":[{"id":"10.13039\/100008904","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms222011265","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T03:01:13Z","timestamp":1634698873000},"page":"11265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Toxic Effects of Indoxyl Sulfate on Osteoclastogenesis and Osteoblastogenesis"],"prefix":"10.3390","volume":"22","author":[{"given":"Jia-Fwu","family":"Shyu","sequence":"first","affiliation":[{"name":"Department of Biology and Anatomy, National Defense Medical Center, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Chih","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biology and Anatomy, National Defense Medical Center, Taipei 110, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-3951","authenticated-orcid":false,"given":"Cai-Mei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University Shuang Ho Hospital, New Taipei City 235, Taiwan"},{"name":"Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Division of Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5577-9280","authenticated-orcid":false,"given":"Te-Chao","family":"Fang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chou","family":"Hou","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Cardinal-Tien Hospital, School of Medicine, Fu-Jen Catholic University, New Taipei City 234, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiz-Tzung","family":"Chang","sequence":"additional","affiliation":[{"name":"College of Medicine, China Medical University, Taichung City 406, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ying","family":"Liao","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City 242, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7062-8560","authenticated-orcid":false,"given":"Kuo-Cheng","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s11914-018-0486-0","article-title":"Ckd-mbd: From the pathogenesis to the identification and development of potential novel therapeutic targets","volume":"16","author":"Elias","year":"2018","journal-title":"Curr. 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