{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T04:38:20Z","timestamp":1761712700182,"version":"build-2065373602"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T00:00:00Z","timestamp":1680566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypertrophic ligamentum flavum (LF) is a main factor responsible for lumbar spinal stenosis (LSS); however, the exact mechanisms of the pathogenesis of these processes remain unknown. This study aimed to elucidate whether circular RNAs and microRNAs regulate the pathogenesis of LF and LSS, especially focusing on circPDK1 (hsa_circ_0057105), a circRNA targeting pyruvate dehydrogenase kinase 1 and differentially expressed in LF tissues between lumbar disk herniation and LSS patients. The circPDK1\/miR\u20104731 and miR\u20104731\/TNXB (Tenascin XB)\u00a0interactions were predicted and validated by luciferase reporter assay. Colony formation, wound\u2010healing, and MTT assays were used for estimating cell proliferation and migration. Protein expression levels were evaluated using Western blotting. TNXB expression was verified using immunohistochemistry (IHC). Overexpressing circPDK1 promoted the proliferation, migration, and expression of fibrosis\u2010related protein (alpha smooth muscle actin (\u03b1\u2010SMA), lysyl oxidase like 2 (LOXL2), Collagen I, matrix metalloproteinase\u20102 (MMP\u20102) and TNXB) in LF whereas miR\u20104731\u20105p showed opposite effects. The expression of TNXB was promoted by circPDK1; contrary results were observed with miR\u20104731\u20105p. Co\u2010overexpression of miR\u20104731\u20105p partially reversed the proliferative and fibrosis\u2010prompting effects of circPDK1 or TNXB. The circPDK1\u2010miR\u20104731\u2010TNXB pathway may be proposed as a regulatory axis in LF hypertrophy, which might shed light on in\u2010depth research of LSS, as well as providing a novel therapeutic target for LF hypertrophy\u2010induced LSS.<\/jats:p>","DOI":"10.1096\/fj.202200022rr","type":"journal-article","created":{"date-parts":[[2023,4,4]],"date-time":"2023-04-04T10:39:42Z","timestamp":1680604782000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Circular\n                    <scp>RNA PDK1<\/scp>\n                    targets\n                    <scp>miR<\/scp>\n                    \u20104731\u20105p to enhance\n                    <scp>TNXB<\/scp>\n                    expression in ligamentum flavum hypertrophy"],"prefix":"10.1096","volume":"37","author":[{"given":"Kai","family":"Zhang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopedics Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopedics Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Ting","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Emergency Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopedics Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3620-1480","authenticated-orcid":false,"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopedics Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,4,4]]},"reference":[{"key":"e_1_2_11_2_1","article-title":"Comparison of lumbar laminectomy alone, lumbar laminectomy and fusion, stand\u2010alone anterior lumbar Interbody fusion, and stand\u2010alone lateral lumbar Interbody fusion for treatment of lumbar spinal stenosis: a review of the literature","volume":"11","author":"Shah 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