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Its aetiology remains to be fully elucidated. This study aimed to clarify its pathogenesis through RNA sequencing of primary cells cultured from patients without cervical OPLL (control, PLL) and patients with cervical OPLL (disease, OPLL). We revealed for the first time the role of GLI1 within OPLL cells. Functional experiments indicated that GLI1, acting as a pivotal mediator between the upstream Hedgehog pathway and downstream BMP pathway, influences the pathogenesis of OPLL. The positive\/negative effects on osteogenic differentiation following activation\/inhibition of the Hedgehog pathway can be rescued by manipulating GLI1 expression. Overexpression of GLI1 activates BMP signalling, enhancing osteogenic capacity in PLL cells, while GLI1 knockdown suppresses BMP signal transduction, attenuating osteogenic differentiation in OPLL cells. Our findings highlight the significant role of the canonical Hedgehog signalling pathway and its interaction with the BMP pathway in the pathogenesis of OPLL.<\/jats:p>","DOI":"10.1111\/jcmm.70393","type":"journal-article","created":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T04:42:16Z","timestamp":1738816936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Hedgehog\u2013GLI1 Pathway Regulates Osteogenic Differentiation of Human Cervical Posterior Longitudinal Ligament Cells by <scp>BMP<\/scp> Signalling Pathway"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4863-5617","authenticated-orcid":false,"given":"Wenbo","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery China\u2010Japan Union Hospital of Jilin University  Jilin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingbing","family":"Ran","sequence":"additional","affiliation":[{"name":"Department of Ultrasound The First Hospital of Jilin University  Jilin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshimi","family":"Aizawa","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery Tohoku University School of Medicine  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanguo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery China\u2010Japan Union Hospital of Jilin University  Jilin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery China\u2010Japan Union Hospital of Jilin University  Jilin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renrui","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery China\u2010Japan Union Hospital of Jilin University  Jilin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeping","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery China\u2010Japan Union Hospital of Jilin University  Jilin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery China\u2010Japan Union Hospital of Jilin University  Jilin People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,2,5]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25143-z"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11237012"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-022-05136-9"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29029-6"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.14245\/ns.1938286.143"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.86514"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/1604932"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-011-1688-7"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000004302"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.119481"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-27514-x"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/2091615"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-394622-5.00022-5"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21020677"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.777532"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-018-0030-y"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2003.07.004"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12013-012-9369-7"},{"issue":"4","key":"e_1_2_11_20_1","first-page":"S11","article-title":"cytoHubba: Identifying Hub Objects and Sub\u2010Networks From Complex Interactome","volume":"8","author":"Chin C. 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