{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T11:32:45Z","timestamp":1780918365672,"version":"3.54.1"},"reference-count":43,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AO Foundation","award":["AOS-Startup-22-032"],"award-info":[{"award-number":["AOS-Startup-22-032"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Adolescent idiopathic scoliosis (AIS) is a multifactorial disease with environmental and genetic components. AIS clinical management is complicated by the lack of reliable predictive markers of progression. Recent studies have highlighted a potential role for epigenetic mechanisms in disease progression. However, most findings derive from peripheral blood analyses, with little data available on musculoskeletal tissues directly affected by AIS. Given the tissue-specific nature of epigenetic regulation, validating blood-based biomarkers in disease-relevant tissues is essential. We performed a comparative multi-gene RT-qPCR analysis, arranged in a custom array format, to assess the local expression of candidate epigenetically regulated genes associated with AIS progression across bone, paravertebral muscle, spinal ligament, and peripheral blood, all collected from the same patients. Tissue- and gene-specific expression patterns were observed, supporting the presence of local regulatory mechanisms. Peripheral blood expression of HAS2, PCDH10, H19, ADIPOQ, ESR1, GREM1, SOX9, FRZB, LRP6, and FBN1 resembled bone expression, while PITX1, CRTC1, APC, CTNNB1, FZD1, and AXIN1 reflected muscle and ligament; WNT1 reflected only muscle. In contrast, GREM1 and SOX9 were expressed only in muscle and ligament and FGF4 and NPY only in muscle, suggesting limited systemic biomarker potential. Compared to non-AIS tissues, AIS samples showed downregulation of PCDH10 and FBN2 in bone and CRTC1, FRZB, LRP6, and MSTN in muscle. WNT1 and WNT10 were upregulated in muscle and FBN1 in ligament. In conclusion, the results highlight differential gene expression across AIS tissues, supporting tissue-specific regulation in some of the genes analyzed. Only a subset of markers exhibited blood expression patterns that reflected those in specific tissues, suggesting that certain blood biomarkers may act as surrogates for distinct tissue compartments. These results lay the groundwork for future DNA-based studies to confirm the epigenetic nature of this regulation and to identify reliable biomarkers for AIS progression.<\/jats:p>","DOI":"10.3390\/ijms26178453","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"8453","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Local Expression of Epigenetic Candidate Biomarkers of Adolescent Idiopathic Scoliosis Progression"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3257-6293","authenticated-orcid":false,"given":"Simona","family":"Neri","sequence":"first","affiliation":[{"name":"Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Ruffilli","sequence":"additional","affiliation":[{"name":"1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5678-6506","authenticated-orcid":false,"given":"Elisa","family":"Assirelli","sequence":"additional","affiliation":[{"name":"Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3992-9637","authenticated-orcid":false,"given":"Marco","family":"Manzetti","sequence":"additional","affiliation":[{"name":"1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4348-0983","authenticated-orcid":false,"given":"Giovanni","family":"Viroli","sequence":"additional","affiliation":[{"name":"1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1524-1811","authenticated-orcid":false,"given":"Matteo","family":"Traversari","sequence":"additional","affiliation":[{"name":"1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2747-5722","authenticated-orcid":false,"given":"Marco","family":"Ialuna","sequence":"additional","affiliation":[{"name":"1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna","family":"Naldi","sequence":"additional","affiliation":[{"name":"Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-7351","authenticated-orcid":false,"given":"Jacopo","family":"Ciaffi","sequence":"additional","affiliation":[{"name":"Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Ursini","sequence":"additional","affiliation":[{"name":"Medicine and Rheumatology Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8152-4778","authenticated-orcid":false,"given":"Cesare","family":"Faldini","sequence":"additional","affiliation":[{"name":"1st Orthopaedic and Traumatologic Clinic, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy"},{"name":"Department of Biomedical and Neuromotor Sciences (DIBINEM), Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11832-012-0457-4","article-title":"Epidemiology of adolescent idiopathic scoliosis","volume":"7","author":"Konieczny","year":"2013","journal-title":"J. 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