{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T01:52:13Z","timestamp":1772761933445,"version":"3.50.1"},"reference-count":47,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,3,30]],"date-time":"2020-03-30T00:00:00Z","timestamp":1585526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Arthritis &amp; Rheumatology"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Increased protein phosphatase magnesium\u2010dependent 1A (<jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A) levels in patients with ankylosing spondylitis regulate osteoblast differentiation in bony ankylosis; however, the potential mechanisms that regulate osteoclast differentiation in relation to abnormal bone formation remain unclear. This study was undertaken to investigate the relationship of <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A to osteoclast differentiation by generating conditional gene\u2010knockout (<jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A<jats:sup>fl\/fl<\/jats:sup>;LysM\u2010Cre) mice and evaluating their bone phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The bone phenotypes of LysM\u2010Cre mice (n = 6) and <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A<jats:sup>fl\/fl<\/jats:sup>;LysM\u2010Cre mice (n = 6) were assessed by micro\u2013computed tomography. Osteoclast differentiation was induced by culturing bone marrow\u2013derived macrophages in the presence of <jats:styled-content style=\"fixed-case\">RANKL<\/jats:styled-content> and macrophage colony\u2010stimulating factor (M\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>), and was evaluated by counting tartrate\u2010resistant acid phosphatase\u2013positive multinucleated cells. Levels of messenger <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> for <jats:italic><jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content><\/jats:italic>, and osteoclast\u2010specific genes were examined by real\u2010time quantitative polymerase chain reaction, and protein levels were determined by Western blotting. Surface <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content> expression was analyzed by fluorescence flow cytometry.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A<jats:sup>fl\/fl<\/jats:sup>;LysM\u2010Cre mice displayed reduced bone mass (<jats:italic>P<\/jats:italic> &lt; 0.001) and increased osteoclast differentiation (<jats:italic>P<\/jats:italic> &lt; 0.001) and osteoclast\u2010specific gene expression (<jats:italic>P<\/jats:italic> &lt; 0.05) compared with their LysM\u2010Cre littermates. Mechanistically, reduced <jats:italic><jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A<\/jats:italic> function in osteoclast precursors in <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A<jats:sup>fl\/fl<\/jats:sup>;LysM\u2010Cre mice induced osteoclast lineage commitment by up\u2010regulating <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content> expression (<jats:italic>P<\/jats:italic> &lt; 0.01) via p38 <jats:styled-content style=\"fixed-case\">MAPK<\/jats:styled-content> activation in response to M\u2010<jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content>. <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A expression in macrophages was decreased by Toll\u2010like receptor 4 activation (<jats:italic>P<\/jats:italic> &lt; 0.05). The Ankylosing Spondylitis Disease Activity Score was negatively correlated with the expression of <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A in peripheral blood mononuclear cells from patients with axial spondyloarthritis (SpA) (\u03b3 = \u22120.7072, <jats:italic>P<\/jats:italic> &lt; 0.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The loss of <jats:italic><jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A<\/jats:italic> function in osteoclast precursors driven by inflammatory signals contributes to osteoclast lineage commitment and differentiation by elevating <jats:styled-content style=\"fixed-case\">RANK<\/jats:styled-content> expression, reflecting a potential role of <jats:styled-content style=\"fixed-case\">PPM<\/jats:styled-content>1A in dynamic bone metabolism in axial SpA.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.41180","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T02:05:28Z","timestamp":1574647528000},"page":"750-760","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Negative Regulation of Osteoclast Commitment by Intracellular Protein Phosphatase Magnesium\u2010Dependent 1A"],"prefix":"10.1002","volume":"72","author":[{"given":"Oh Chan","family":"Kwon","sequence":"first","affiliation":[{"name":"University of Ulsan College of Medicine Asan Medical Center, and Yonsei University College of Medicine  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bongkun","family":"Choi","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun\u2010Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji\u2010Eun","family":"Park","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun\u2010Ju","family":"Lee","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun\u2010Young","family":"Kim","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang\u2010Min","family":"Kim","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min\u2010Kyung","family":"Shin","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3542-2276","authenticated-orcid":false,"given":"Tae\u2010Hwan","family":"Kim","sequence":"additional","affiliation":[{"name":"Hanyang University Hospital for Rheumatic Diseases  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seokchan","family":"Hong","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2010Keun","family":"Lee","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Yoo","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William H.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine  Stanford California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8029-7355","authenticated-orcid":false,"given":"Yong\u2010Gil","family":"Kim","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun\u2010Ju","family":"Chang","sequence":"additional","affiliation":[{"name":"University of Ulsan College of Medicine and Asan Medical Center  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,3,30]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1406182"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23738"},{"key":"e_1_2_6_4_1","first-page":"5","article-title":"Ankylosing spondylitis patients have impaired osteoclast gene expression in circulating osteoclast precursors","volume":"4","author":"Perp\u00e9tuo IP","year":"2017","journal-title":"Front Med (Lausanne)"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0144655"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/gls163"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.156"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-200307000-00004"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.79"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01658"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.190.12.1741"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M200434200"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.18.2412"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116179"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2013.1258"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.13814"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng2076"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.8.8954"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M001229200"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2005.11.007"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1885"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2011.23"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1210\/edrv.20.3.0367"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri2062"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(00)00424-X"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.38763"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8190"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/17.16.4744"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40240"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24626"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2009.108233"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.094870"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81569-X"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.4110\/in.2018.18.e8"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034513500306"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2014.07.022"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2006.00796.x"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.189.4.615"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.7.3749"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780270401"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1593"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2002-220467"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.4236\/abb.2012.35077"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2006-0165OC"},{"key":"e_1_2_6_45_1","first-page":"65","article-title":"Osteoclast formation and differentiation: an overview","volume":"59","author":"Soysa NS","year":"2012","journal-title":"J Med Dent Sci"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/ken176"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kel072"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.10139"}],"updated-by":[{"DOI":"10.1002\/art.41495","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:00:00Z","timestamp":1598572800000}}],"container-title":["Arthritis &amp; Rheumatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41180","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/art.41180","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/art.41180","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T19:41:40Z","timestamp":1759952500000},"score":1,"resource":{"primary":{"URL":"https:\/\/acrjournals.onlinelibrary.wiley.com\/doi\/10.1002\/art.41180"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,30]]},"references-count":47,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,5]]}},"alternative-id":["10.1002\/art.41180"],"URL":"https:\/\/doi.org\/10.1002\/art.41180","archive":["Portico"],"relation":{"erratum":[{"id-type":"doi","id":"10.1002\/art.41495","asserted-by":"object"}]},"ISSN":["2326-5191","2326-5205"],"issn-type":[{"value":"2326-5191","type":"print"},{"value":"2326-5205","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,30]]},"assertion":[{"value":"2019-01-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-21","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-03-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}