{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:33:13Z","timestamp":1772166793733,"version":"3.50.1"},"reference-count":56,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100006396","name":"Alexion","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Adult hypophosphatasia (HPP) patients present with diffuse heterogenous symptoms often mimicking rheumatological diseases or osteoporosis and therefore accompanied by delayed diagnosis. The aim of this study was to identify circulating microRNAs (miRNAs) in adult HPP patients and to identify potential associations with clinical patients' characteristics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We utilized untargeted miRNA biomarker discovery by small RNA-sequencing to investigate cell-free miRNA profiles in 24 adult HPP patients (pathogenic variant of the ALPL gene, HPP-related clinical symptoms, and repeatedly low alkaline phosphatase) and 24 healthy controls (CTRL).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients and CTRL were comparable in age (47.9 \u00b1 14.2 vs 45.9 \u00b1 8.8 years, P = .980) and sex (55.5% vs 47.8% females, P = 1.000). In total, 91% of patients reported musculoskeletal pain, 41% diffuse neurological symptoms, and 64% history of fractures. In total, 84 miRNAs were significantly differently expressed between HPP and CTRL in next-generation sequencing analysis (P &amp;lt; .05). Of these, 14 miRNAs were selected (selection criteria: P &amp;lt; .05, tissue specificity index &amp;gt;0.7, log2 fold change &amp;gt;+0.8 or &amp;lt;\u22120.8) for validation using RT-qualitative PCR, which verified 6 of 14 selected miRNAs (P &amp;lt; .05; miR-122-3p, miR-140-5p, miR-143-3p, miR-155-5p, miR-451a, miR-92a-3p). Target prediction and enrichment analysis identified associations with the musculoskeletal system and the central nervous system. In total, 37 miRNAs correlated with alkaline phosphatase levels, but only 3 miRNAs with pyridoxal-5\u2032-phosphate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight a profound involvement of multiple organ systems and the potential of miRNAs as biomarkers for the effect of HPP on various systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trials No<\/jats:title>\n                    <jats:p>NCT04018287<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgaf080","type":"journal-article","created":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T15:20:09Z","timestamp":1739200809000},"page":"2741-2751","source":"Crossref","is-referenced-by-count":0,"title":["Circulating Micro-RNAs in Patients With Hypophosphatasia: Results of the First Micro-RNA Analysis in HPP"],"prefix":"10.1210","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-6785","authenticated-orcid":false,"given":"Judith","family":"Haschka","sequence":"first","affiliation":[{"name":"Hanusch Hospital, 1st Medical Department, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling , 1140 Vienna ,","place":["Austria"]},{"name":"Vienna Bone and Growth Center , Vienna ,","place":["Austria"]},{"name":"Karl Landsteiner Institute for Osteology and Rheumatology, Rheuma-Zentrum Wien-Oberlaa , 1100 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zora","family":"Messner","sequence":"additional","affiliation":[{"name":"Barmherzige Schwestern Krankenhaus Wien , 2nd Medical Department, 1060 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia","family":"Feurstein","sequence":"additional","affiliation":[{"name":"Hanusch Hospital, 1st Medical Department, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling , 1140 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8079-2973","authenticated-orcid":false,"given":"Benjamin","family":"Hadzimuratovic","sequence":"additional","affiliation":[{"name":"Hanusch Hospital, 1st Medical Department, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling , 1140 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jochen","family":"Zwerina","sequence":"additional","affiliation":[{"name":"Hanusch Hospital, 1st Medical Department, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling , 1140 Vienna ,","place":["Austria"]},{"name":"Vienna Bone and Growth Center , Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0331-9685","authenticated-orcid":false,"given":"Andreas B","family":"Diendorfer","sequence":"additional","affiliation":[{"name":"TAmiRNA GmbH , 1110 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marianne","family":"Pultar","sequence":"additional","affiliation":[{"name":"TAmiRNA GmbH , 1110 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4136-7293","authenticated-orcid":false,"given":"Matthias","family":"Hackl","sequence":"additional","affiliation":[{"name":"TAmiRNA GmbH , 1110 Vienna ,","place":["Austria"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Kuzma","sequence":"additional","affiliation":[{"name":"Comenius University Faculty of Medicine, University Hospital Bratislava , 81107 Bratislava 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