{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T04:09:01Z","timestamp":1792382941950,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T00:00:00Z","timestamp":1500508800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:p>\n                    Abnormalities of bone turnover are commonly observed in patients with chronic kidney disease (\n                    <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n                    ), and the low\u2010turnover bone disease is considered to be associated with low serum parathyroid hormone (\n                    <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>\n                    ) levels and skeletal resistance to\n                    <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>\n                    . Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood of patients with\n                    <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n                    . Recently, we have reported that IS exacerbates low bone turnover induced by parathyroidectomy (PTX) in adult rats, and suggested that IS directly induces low bone turnover through the inhibition of bone formation by mechanisms unrelated to skeletal resistance to\n                    <jats:styled-content style=\"fixed-case\">PTH<\/jats:styled-content>\n                    . To define the direct action of IS in bone turnover, we examined the effects of IS on bone formation and bone resorption\n                    <jats:italic>in vitro<\/jats:italic>\n                    . In cultures of mouse primary osteoblasts, IS suppressed the expression of osterix, osteocalcin, and bone morphogenetic protein 2 (BMP2)\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    and clearly inhibited the formation of mineralized bone nodules. Therefore, IS directly acts on osteoblastic cells to suppress bone formation. On the other hand, IS suppressed interleukin (\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    )\u20101\u2010induced osteoclast formation in cocultures of bone marrow cells and osteoblasts, and\n                    <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\n                    \u20101\u2010induced bone resorption in calvarial organ cultures. In cultures of osteoblasts, IS suppressed the\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    expression of\n                    <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>\n                    , the receptor activator of\n                    <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\n                    \u2010\u03baB ligand, which is a pivotal factor for osteoclast differentiation. Moreover, IS acted on osteoclast precursor, bone marrow\u2010derived macrophages and\n                    <jats:styled-content style=\"fixed-case\">RAW<\/jats:styled-content>\n                    264.7 cells, and suppressed\n                    <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content>\n                    \u2010dependent differentiation into mature osteoclasts. IS may induce low\u2010turnover bone disease in patients with\n                    <jats:styled-content style=\"fixed-case\">CKD<\/jats:styled-content>\n                    by its direct action on both osteoblasts and osteoclast precursors to suppress bone formation and bone resorption.\n                  <\/jats:p>","DOI":"10.1002\/2211-5463.12258","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T02:14:42Z","timestamp":1497838482000},"page":"1178-1185","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Indoxyl sulfate, a uremic toxin in chronic kidney disease, suppresses both bone formation and bone resorption"],"prefix":"10.1002","volume":"7","author":[{"given":"Kenta","family":"Watanabe","sequence":"first","affiliation":[{"name":"Cooperative Major of Advanced Health Science Tokyo University of Agriculture and Technology Koganei 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