{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:48:30Z","timestamp":1786978110785,"version":"build-2736575974"},"reference-count":24,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T00:00:00Z","timestamp":1564617600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006468","name":"College of Medicine, Korea University","doi-asserted-by":"publisher","award":["K1808641"],"award-info":[{"award-number":["K1808641"]}],"id":[{"id":"10.13039\/501100006468","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006468","name":"College of Medicine, Korea University","doi-asserted-by":"publisher","award":["K1722461"],"award-info":[{"award-number":["K1722461"]}],"id":[{"id":"10.13039\/501100006468","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006468","name":"College of Medicine, Korea University","doi-asserted-by":"publisher","award":["K1809751"],"award-info":[{"award-number":["K1809751"]}],"id":[{"id":"10.13039\/501100006468","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Ligamentum flavum hypertrophy (LFH) is the most important component of lumbar spinal canal stenosis. Although the pathophysiology of LFH has been extensively studied, no method has been proposed to prevent or treat it. Since the transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) pathway is known to be critical in LFH pathology, we investigated whether LFH could be prevented by blocking or modulating the TGF\u2010\u03b2 mechanism. Human LF cells were used for the experiments. First, we created TGF\u2010\u03b2 receptor 1 (TGFBR1) knock out (KO) cells with CRISPR (clustered regularly interspaced short palindromic repeats)\/Cas9 biotechnology and treated them with TGF\u2010\u03b21 to determine the effects of blocking the TGF\u2010\u03b2 pathway. Subsequently, we studied the effect of CCN5, which has recently been proposed to modulate the TGF\u2010\u03b2 pathway. To assess the predisposition toward fibrosis, \u03b1\u2010smooth muscle actin (\u03b1SMA), fibronectin, collagen\u20101, collagen\u20103, and CCN2 were evaluated with quantitative real\u2010time polymerase chain reaction, western blotting, and immunocytochemistry. The TGFBR1 KO LF cells were successfully constructed with high KO efficiency. In wild\u2010type (WT) cells, treatment with TGF\u2010\u03b21 resulted in the overexpression of the messenger RNA (mRNA) of fibrosis\u2010related factors. However, in KO cells, the responses to TGF\u2010\u03b21 stimulation were significantly lower. In addition, CCN5 and TGF\u2010\u03b21 co\u2010treatment caused a notable reduction in mRNA expression levels compared with TGF\u2010\u03b21 stimulation only. The \u03b1SMA protein expression increased with TGF\u2010\u03b21 but decreased with CCN5 treatment. TGF\u2010\u03b21 induced LF cell transdifferentiation from fibroblasts to myofibroblasts. However, this cell transition dramatically decreased in the presence of CCN5. In conclusion, CCN5 could prevent LFH by modulating the TGF\u2010\u03b2 pathway.  \u00a9 2019 The Authors.\n                    <jats:italic>Journal of Orthopaedic Research<\/jats:italic>\n                    <jats:sup>\u00ae<\/jats:sup>\n                    published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 37:2634\u20132644, 2019\n                  <\/jats:p>","DOI":"10.1002\/jor.24425","type":"journal-article","created":{"date-parts":[[2019,7,23]],"date-time":"2019-07-23T10:26:14Z","timestamp":1563877574000},"page":"2634-2644","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["CCN5 Reduces Ligamentum Flavum Hypertrophy by Modulating the TGF\u2010\u03b2 Pathway"],"prefix":"10.1002","volume":"37","author":[{"given":"Sunghyeok","family":"Ye","sequence":"first","affiliation":[{"name":"RnD center GeneCker  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woo\u2010Keun","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine Korea University Anam Hospital  73, Inchon\u2010ro, Seongbuk\u2010gu Seoul 02841 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taegeun","family":"Bae","sequence":"additional","affiliation":[{"name":"Department of Medicine, Graduate School Kyung Hee University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunghyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Molecular and Computational Biology University of Southern California  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jang\u2010Bo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine Korea University Anam Hospital  73, Inchon\u2010ro, Seongbuk\u2010gu Seoul 02841 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai\u2010Hyoung","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine Korea University Anam Hospital  73, Inchon\u2010ro, Seongbuk\u2010gu Seoul 02841 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung\u2010Yul","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, College of Medicine Korea University Anam Hospital  73, Inchon\u2010ro, Seongbuk\u2010gu Seoul 02841 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoungmi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Department of Physiology, College of Medicine Korea University  Seoul Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3794-1149","authenticated-orcid":false,"given":"Junho K.","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine Kyung Hee University  26, Kyungheedae\u2010ro, Dongdaemun\u2010gu Seoul 02447 Korea"},{"name":"Department of Biomedical Sciences, Graduate School Kyung Hee University  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