{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T21:36:11Z","timestamp":1789940171629,"version":"4.0.1"},"reference-count":22,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,11,11]],"date-time":"2018-11-11T00:00:00Z","timestamp":1541894400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016R1A2B4008606"],"award-info":[{"award-number":["2016R1A2B4008606"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2017R1A6A3A11034394"],"award-info":[{"award-number":["2017R1A6A3A11034394"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI17C0888"],"award-info":[{"award-number":["HI17C0888"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Ankylosing spondylitis (AS) is characterized by excessive spinal ankylosis and bone formation. Alkaline phosphatase (ALP) activity is reported to be high in AS, but little is known about the molecular relationship between ALP and AS. The aims of this study were to investigate the relevance of ALP to AS and the role of ALP in the regulation of osteoblast differentiation in AS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>High\u2010throughput data with accession numbers GSE73754 and GSE41038 were downloaded from the Gene Expression Omnibus. We retrospectively collected and compared the ALP levels of male patients with AS to those of sex\u2010 and age\u2010matched healthy controls (HC) and rheumatoid arthritis (RA) patients. Total serum ALP and ALP activity were measured in the AS and RA groups. ALP gene expression and intracellular ALP activity were analyzed in microarray data from primary diseases control (Ct) and AS\u2010bone\u2010derived cells (BdCs) and in vitro experiments. Furthermore, the effect of ALP inhibitor was examined in both primary Ct\u2010 and AS\u2010BdCs under osteoblast differentiation. Regulation of runt\u2010related transcription factor 2 (RUNX2) by ALP was also analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Alkaline phosphatase level was higher in AS compared with RA and HC and was associated with radiograph progression. ALP expression was also enriched in the bone tissue of AS patients. Furthermore, AS\u2010BdCs exhibited increasing ALP activity, leading to accelerated osteoblastic activity and differentiation. Intriguingly, inhibition of ALP reduced RUNX2 expression, a master transcriptional factor in osteoblasts, and differentiation status of both primary Ct\u2010 and AS\u2010BdCs. Treatment of ALP activator or inhibitor modulated RUNX2 protein level and RUNX2 regulated ALP promoter activity, indicating a reciprocal ALP\u2010RUNX2 positive feedback to regulate osteoblast differentiation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Alkaline phosphatase was highly expressed in AS patients, may be involved in the ankylosis of AS, and represents a possible therapeutic target for ankylosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1756-185x.13419","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T00:25:16Z","timestamp":1541982316000},"page":"252-261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["Regulation of osteoblasts by alkaline phosphatase in ankylosing spondylitis"],"prefix":"10.1111","volume":"22","author":[{"given":"Sungsin","family":"Jo","sequence":"first","affiliation":[{"name":"Hanyang University Hospital for Rheumatic Diseases Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinil","family":"Han","sequence":"additional","affiliation":[{"name":"Gencurix, Inc Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young L.","family":"Lee","sequence":"additional","affiliation":[{"name":"Hanyang University Hospital for Rheumatic Diseases Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subin","family":"Yoon","sequence":"additional","affiliation":[{"name":"Hanyang University Hospital for Rheumatic Diseases Seoul Korea"},{"name":"Department of Translational Medicine, Graduate School of Biomedical Science and Engineering Hanyang University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaehyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Hanyang University Hospital for Rheumatic Diseases Seoul Korea"},{"name":"Department of Translational Medicine, Graduate School of Biomedical Science and Engineering Hanyang University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung E.","family":"Wang","sequence":"additional","affiliation":[{"name":"Hanyang Biomedical Research Institute Hanyang University Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,11,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39433"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774-017-0846-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.4078\/jrd.2015.22.2.61"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0805-0"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.4078\/jrd.2016.23.6.356"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/13102818.2007.10817444"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2000.15.10.1879"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.42.5.563"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2015.03.002"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2011.09.007"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.11.155"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-018-1582-3"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.020503"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.12887"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.07.079"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39464"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.20446"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/195911a0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701116200"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2002.17.5.669"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.44.6.359"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-015-0675-5"}],"container-title":["International Journal of Rheumatic Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2F1756-185X.13419","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/1756-185X.13419","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T17:07:42Z","timestamp":1694711262000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/1756-185X.13419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11,11]]},"references-count":22,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1111\/1756-185X.13419"],"URL":"https:\/\/doi.org\/10.1111\/1756-185x.13419","archive":["Portico"],"relation":{},"ISSN":["1756-1841","1756-185X"],"issn-type":[{"value":"1756-1841","type":"print"},{"value":"1756-185X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,11,11]]},"assertion":[{"value":"2018-06-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}