{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T07:27:37Z","timestamp":1767598057614,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,1,26]],"date-time":"2025-01-26T00:00:00Z","timestamp":1737849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MEDTEQ (Minist\u00e8re du D\u00e9veloppement \u00c9conomique et de l\u2019Innovation du Qu\u00e9bec)","award":["12-R-SAMBA","12-R-SAMBA","12-R-SAMBA","IT16239"],"award-info":[{"award-number":["12-R-SAMBA","12-R-SAMBA","12-R-SAMBA","IT16239"]}]},{"name":"Medtronic Canada, La Fondation Yves Cotrel de l\u2019Institut de France","award":["12-R-SAMBA","12-R-SAMBA","12-R-SAMBA","IT16239"],"award-info":[{"award-number":["12-R-SAMBA","12-R-SAMBA","12-R-SAMBA","IT16239"]}]},{"name":"Montreal TransMedTech Institute","award":["12-R-SAMBA","12-R-SAMBA","12-R-SAMBA","IT16239"],"award-info":[{"award-number":["12-R-SAMBA","12-R-SAMBA","12-R-SAMBA","IT16239"]}]},{"DOI":"10.13039\/501100004489","name":"MITACS (Canada)","doi-asserted-by":"publisher","award":["12-R-SAMBA","12-R-SAMBA","12-R-SAMBA","IT16239"],"award-info":[{"award-number":["12-R-SAMBA","12-R-SAMBA","12-R-SAMBA","IT16239"]}],"id":[{"id":"10.13039\/501100004489","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adolescent idiopathic scoliosis (AIS) is characterized by a curvature of the spine affecting approximately 4% of the pediatric population, and the mechanisms driving its progression remain poorly understood. Whole-exome sequencing of a French-Canadian AIS cohort with severe scoliosis identified rare variants in the PTPRM gene, which encodes Protein Tyrosine Phosphatase \u03bc (PTP\u00b5). However, these rare variants alone did not account for the pronounced reduction in PTP\u00b5 at both mRNA and protein levels in severe AIS cases. This led us to investigate epigenetic regulators and the identification of five microRNAs (miR-103a-3p, miR-107, miR-148a-3p, miR-148b-3p, and miR-152-3p) that target PTPRM mRNA. These microRNAs were significantly elevated in plasma from severe AIS patients, and miR-148b-3p was also upregulated in AIS osteoblasts. Phenotypic analysis of bipedal Ptrprm knockout (PTP\u00b5 \u2212\/\u2212) mice showed increased prevalence and severity of scoliosis, while quadrupedal PTP\u00b5 \u2212\/\u2212 mice did not develop scoliosis, underscoring PTP\u00b5\u2019s role as a disease-modifying factor. Mechanistically, PTP\u00b5 deficiency was found to disrupt Gi-coupled receptor signaling in osteoblasts by enhancing the interaction between osteopontin (OPN) and \u03b15\u03b21 integrin, along with increased tyrosine phosphorylation of phosphatidylinositol-4-phosphate 5-kinase type I (PIPKI\u03b390). These findings provide novel insights into the molecular mechanisms underlying spinal deformity progression in AIS, linking PTP\u00b5 depletion to aberrant OPN-\u03b15\u03b21 integrin signaling and highlighting potential therapeutic targets to stop, mitigate, or prevent scoliosis.<\/jats:p>","DOI":"10.3390\/ijms26031042","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T03:54:27Z","timestamp":1737950067000},"page":"1042","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Loss of Tyrosine Phosphatase Mu Promotes Scoliosis Progression Through Osteopontin-\u03b15\u03b21 Integrin Signaling and PIPK1\u03b390 Activity"],"prefix":"10.3390","volume":"26","author":[{"given":"Mohamed","family":"Elbakry","sequence":"first","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montr\u00e9al, QC H3T 1C5, Canada"},{"name":"Department of Chemistry, Biochemistry Section, Faculty of Science, Tanta University, Tanta 31527, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1684-7292","authenticated-orcid":false,"given":"Nasrin","family":"Khatami","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montr\u00e9al, QC H3T 1C5, Canada"},{"name":"Department of Biochemistry and Molecular Medicine, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Yvonne","family":"Akoume","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montr\u00e9al, QC H3T 1C5, Canada"},{"name":"Department of Cellular, Molecular Biology and Genetics, Faculty of Medicine, Universit\u00e9 des Sciences de la Sant\u00e9 (USS) de Libreville, Libreville BP 18231, Gabon"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9dric","family":"Julien","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montr\u00e9al, QC H3T 1C5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saadallah","family":"Bouhanik","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montr\u00e9al, QC H3T 1C5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Franco","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montr\u00e9al, QC H3T 1C5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iurie","family":"Caraus","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montr\u00e9al, QC H3T 1C5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3577-3551","authenticated-orcid":false,"given":"Wesam","family":"Elremaly","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montr\u00e9al, QC H3T 1C5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Moreau","sequence":"additional","affiliation":[{"name":"Viscogliosi Laboratory in Molecular Genetics of Musculoskeletal Diseases, Azrieli Research Center, CHU Sainte-Justine, Montr\u00e9al, QC H3T 1C5, Canada"},{"name":"Department of Cellular, Molecular Biology and Genetics, Faculty of Medicine, Universit\u00e9 des Sciences de la Sant\u00e9 (USS) de Libreville, Libreville BP 18231, Gabon"},{"name":"Department of Stomatology, Faculty of Dentistry, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC H3T 1J4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15030","DOI":"10.1038\/nrdp.2015.30","article-title":"Adolescent idiopathic scoliosis","volume":"1","author":"Cheng","year":"2015","journal-title":"Nat. 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