{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T22:43:45Z","timestamp":1772577825626,"version":"3.50.1"},"reference-count":44,"publisher":"The Company of Biologists","issue":"4","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"European Research Council","award":["311723-GENEPAD"],"award-info":[{"award-number":["311723-GENEPAD"]}]},{"name":"European Research Council","award":["787270-Paget-Advance"],"award-info":[{"award-number":["787270-Paget-Advance"]}]},{"name":"The Paget's Association"},{"DOI":"10.13039\/501100000848","name":"University of Edinburgh","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000848","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Paget's disease of bone (PDB) is characterized by focal increases in bone remodelling. Genome-wide association studies identified a susceptibility locus for PDB tagged by rs5742915, which is located within the PML gene. Here, we have assessed the candidacy of PML as the predisposing gene for PDB at this locus. We found that the PDB-risk allele of rs5742915 was associated with lower PML expression and that PML expression in blood cells from individuals with PDB was lower than in controls. The differentiation, survival and resorptive activity of osteoclasts prepared from Pml\u2212\/\u2212 mice was increased compared with wild type. Furthermore, the inhibitory effect of IFN-\u03b3 on osteoclast formation from Pml\u2212\/\u2212 was significantly blunted compared with wild type. Bone nodule formation was also increased in osteoblasts from Pml\u2212\/\u2212 mice when compared with wild type. Although microCT analysis of trabecular bone showed no differences between Pml\u2212\/\u2212 mice and wild type, bone histomorphometry showed that Pml\u2212\/\u2212 mice had high bone turnover with increased indices of bone resorption and increased mineral apposition rate. These data indicate that reduced expression of PML predisposes an individual to PDB and identify PML as a novel regulator of bone metabolism.<\/jats:p>\n               <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/dmm.049318","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T09:27:20Z","timestamp":1646126840000},"source":"Crossref","is-referenced-by-count":9,"title":["The Paget's disease of bone risk gene <i>PML<\/i> is a negative regulator of osteoclast differentiation and bone resorption"],"prefix":"10.1242","volume":"15","author":[{"given":"Sachin","family":"Wani","sequence":"first","affiliation":[{"name":"Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Daroszewska","sequence":"additional","affiliation":[{"name":"Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald M.","family":"Salter","sequence":"additional","affiliation":[{"name":"Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rob J.","family":"van \u2018t Hof","sequence":"additional","affiliation":[{"name":"Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK"},{"name":"Vanthof Scientific, Torun 87-100, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stuart H.","family":"Ralston","sequence":"additional","affiliation":[{"name":"Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5916-5983","authenticated-orcid":false,"given":"Omar M. E.","family":"Albagha","sequence":"additional","affiliation":[{"name":"Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK"},{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, P.O. Box 34110, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"2022042712013246300_DMM049318C1","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/ng.562","article-title":"Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget's disease of bone","volume":"42","author":"Albagha","year":"2010","journal-title":"Nat. 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