{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T14:38:28Z","timestamp":1774276708159,"version":"3.50.1"},"reference-count":7,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,4]]},"abstract":"\n Study Design:<\/jats:title>\n Histologic, immunohistochemical (IHC), and enzyme-linked immunosorbent assay analysis of the human ligamentum flavum (LF).<\/jats:p>\n <\/jats:sec>\n \n Objective:<\/jats:title>\n The purpose of this study was to determine the level of expression of lysophosphatidic acid (LPA) in the LF from lumbar spinal stenosis (LSS) patients and to analyze the relationship among LPA, LPA receptors (LPARs), and LF hypertrophy.<\/jats:p>\n <\/jats:sec>\n \n Summary of Background Data:<\/jats:title>\n LF hypertrophy and fibrosis are important causes of LSS. LPA is involved in the fibrotic process in multiple organ systems. Therefore, we hypothesized that LPA and its receptors might also play a role in degeneration of the LF in LSS patients.<\/jats:p>\n <\/jats:sec>\n \n Methods:<\/jats:title>\n Forty-one LF samples were enrolled in this study. The thickness of the LF was measured by magnetic resonance imaging. Histologic analysis using hematoxylin and eosin and Masson trichrome stain was performed for each LF to evaluate the architecture of the extracellular matrix. The content of LPA and connective tissue growth factor (CTGF) in LF samples was analyzed using enzyme-linked immunosorbent assay. The expression of LPAR1 was determined by IHC.<\/jats:p>\n <\/jats:sec>\n \n Results:<\/jats:title>\n Degeneration of the LF was characterized by an increase in disorganized elastic fibers and fibrotic transformation by extracellular collagen deposition. The thickness of the LF and the concentration of LPA and CTGF in the hypertrophic LF group were significantly higher than the control group. Furthermore, the LPA and CTGF concentrations had a positive correlation with the LF thickness (r<\/jats:italic>=0.91, P<\/jats:italic><0.001 and r<\/jats:italic>=0.943, P<\/jats:italic><0.001, respectively). On the basis of IHC analysis, the expression of LPAR1 was increased in the hypertrophy group.<\/jats:p>\n <\/jats:sec>\n \n Conclusions:<\/jats:title>\n The increased expression of LPA and LPAR1 is associated with the fibrosis and hypertrophy of the LF in patients with LSS. Further study on the mechanism underlying LF fibrosis may lead to new therapies for LF hypertrophy and fibrosis.<\/jats:p>\n <\/jats:sec>","DOI":"10.1097\/bsd.0000000000000048","type":"journal-article","created":{"date-parts":[[2013,11,18]],"date-time":"2013-11-18T21:02:42Z","timestamp":1384808562000},"page":"E189-E191","source":"Crossref","is-referenced-by-count":19,"title":["Hypertrophy and Fibrosis of the Ligamentum Flavum in Lumbar Spinal Stenosis is Associated With Increased Expression of LPA and LPAR1"],"prefix":"10.1097","volume":"30","author":[{"given":"Kai","family":"Zhang","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin-yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, PR China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang-qing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-jiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xie","family":"You-zhuan","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Ding","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People\u2019s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230831","doi-asserted-by":"crossref","first-page":"2805","DOI":"10.1097\/BRS.0b013e31815b650f","article-title":"Pathomechanism of loss of elasticity and hypertrophy of lumbar ligamentum flavum in elderly patients with lumbar spinal canal stenosis","volume":"32","author":"Kosaka","year":"2007","journal-title":"Spine"},{"key":"R2-20230831","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.prostaglandins.2009.02.002","article-title":"Lysophosphatidic acid (LPA) receptors: signaling properties and disease relevance","volume":"91","author":"Lin","year":"2010","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"R3-20230831","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1517\/13543784.2011.566864","article-title":"Lysophosphatidic acid-1-receptor targeting agents for fibrosis","volume":"20","author":"Rancoule","year":"2011","journal-title":"Expert Opin Investig Drugs"},{"key":"R4-20230831","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1002\/jor.21431","article-title":"Hypertrophy of ligamentum flavum in lumbar spine stenosis associated with the increased expression of connective tissue growth factor","volume":"29","author":"Zhong","year":"2011","journal-title":"J Orthop Res"},{"key":"R5-20230831","doi-asserted-by":"crossref","first-page":"E340","DOI":"10.1097\/01.brs.0000263407.25009.6e","article-title":"Lumbar ligamentum flavum hypertrophy is due to accumulation of inflammation-related scar tissue","volume":"32","author":"Sairyo","year":"2007","journal-title":"Spine (Phila Pa 1976)"},{"key":"R6-20230831","doi-asserted-by":"crossref","first-page":"E6","DOI":"10.1097\/BSD.0b013e3182698501","article-title":"Inflammatory cytokines induce fibrosis and ossification of human ligamentum flavum cells","volume":"26","author":"Park","year":"2013","journal-title":"J Spinal Disord Tech"},{"key":"R7-20230831","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1097\/BSD.0b013e3182495b88","article-title":"Expression of hypoxia-inducible factor-1 alpha, vascular endothelial growth factor, and matrix metalloproteinases 1, 3, and 9 in hypertrophied ligamentum flavum","volume":"26","author":"Lakemeier","year":"2013","journal-title":"J Spinal Disord Tech"}],"container-title":["Clinical Spine Surgery: A Spine Publication"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/01933606-201704000-00016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T18:34:58Z","timestamp":1693506898000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01933606-201704000-00016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,4]]},"references-count":7,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1097\/bsd.0000000000000048","relation":{},"ISSN":["2380-0186"],"issn-type":[{"value":"2380-0186","type":"print"}],"subject":[],"published":{"date-parts":[[2017,4]]}}}