{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T14:43:50Z","timestamp":1780497830880,"version":"3.54.1"},"reference-count":54,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T00:00:00Z","timestamp":1595376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FEBS Open Bio"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>Niclosamide is a potent inhibitor of osteoclastogenesis and bone remodeling. DK\u2010520 is an acyl derivative of Niclosamide and significantly increased both the plasma concentration and the duration of exposure of Niclosamide when dosed orally. However, at present the effect of DK\u2010520 on osteoclastogenesis has not been reported. Here, we investigated whether DK\u2010520 can regulate receptor activator of nuclear factor\u2010\u03baB ligand (RANKL)\u2010induced osteoclastogenesis of bone marrow macrophages (BMMs) <jats:italic>in\u00a0vitro<\/jats:italic>. Following induction of BMMs with RANKL for three days, we detected differentiated osteoclasts with typical morphology and high levels of tartrate\u2010resistant acid phosphatase (TRAP), RANKL, and cathepsin K (CTSK) expression. Treatment with either Niclosamide or DK\u2010520 did not affect the viability of osteoclast precursors (OCPs), but significantly inhibited RANKL\u2010induced transdifferentiation of macrophages into OCPs, particularly in the early stage of osteoclastogenesis. Both Niclosamide and DK\u2010520 significantly decreased the relative levels of transcription factor PU.1 mRNA transcripts and dendritic cell\u2010specific transmembrane protein (DC\u2010STAMP), but not v\u2010ATPasev<jats:sub>0<\/jats:sub>d<jats:sub>2<\/jats:sub> protein expression in OCPs. In addition, the inhibitory effect of DK\u2010520 on osteoclastogenesis is realized through impairment of the NF\u2010kB (nuclear factor\u2010\u03baB) and MAPK (mitogen\u2010activated protein kinase) signaling pathways. These results demonstrate that DK\u2010520, like Niclosamide, effectively inhibits the early stage of osteoclastogenesis. The findings presented here, together with its increased oral plasma concentrations and bioavailability, suggest that DK\u2010520 may be a promising drug candidate for treatment of osteoclast\u2010related diseases.<\/jats:p>","DOI":"10.1002\/2211-5463.12921","type":"journal-article","created":{"date-parts":[[2020,6,30]],"date-time":"2020-06-30T02:34:51Z","timestamp":1593484491000},"page":"1685-1697","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Niclosamide and its derivative DK\u2010520 inhibit RANKL\u2010induced osteoclastogenesis"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1052-0531","authenticated-orcid":false,"given":"Yurui","family":"Jiao","sequence":"first","affiliation":[{"name":"Department of Endocrinology The Second Hospital of Shanxi Medical University Taiyuan 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