{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:12:58Z","timestamp":1788847978787,"version":"build-2803163510"},"reference-count":50,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,3,1]],"date-time":"2019-03-01T00:00:00Z","timestamp":1551398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lumbar spinal canal stenosis (LSCS) is a degenerative disease observed by hypertrophy of the ligamentum flavum (LF) that cause compression of the lumbar neural content. Diabetes mellitus (DM) is a risk factor for the disease and we have shown previously that DM increases the fibrosis and elastic fiber loss in patients with LSCS. The purpose of this study was to find the proteins that play a role in the development of this clinical pathogenesis and the effect of DM on protein expression. LF tissue retrieved from patients diagnosed with LSCS, some were also diagnosed with DM, were compared with LF from patients diagnosed with herniated nucleus pulposus (HNP). The tissues were analyzed by mass spectrometry for proteins profile alteration. We found that LF of LSCS\/DM patients exhibited significantly higher levels of proteoglycan proteins and latent transforming growth factor \u03b2\u2010binding protein (LTBP2 and LTBP4). Additionally, an increase of HTRA serine protease 1 and insulin\u2010like growth factor binding protein\u20105 were noted. The higher fibrosis was also associated with proteins related to inflammation and slower tissue repair. Collagen 6 and transforming growth factor inhibitor are related to activation of the anti\u2010inflammatory M2 pathway that is associated with tissue repair. The decrease of these proteins expression in LSCS\/DM is associated with increased levels and activation of M1 pro\u2010inflammatory pathways. Interestingly, C3 and C4b members of the complement complex and mannose receptor\u2010like protein (CLEC18) paralogous proteins were detectable solely at the LSCS\/DM patients\u2019 samples. Histology analysis shows that inflammatory was induced by the hyperglycemic conditions in diabetic patients involve in altering the matrix compositions. Thus, the protein profiles associated with inflammatory pathways affecting the LF suggested increasing susceptibility of developing the degeneration under hyperglycemic conditions.<\/jats:p>","DOI":"10.1002\/jcb.28451","type":"journal-article","created":{"date-parts":[[2019,3,2]],"date-time":"2019-03-02T07:40:05Z","timestamp":1551512405000},"page":"11716-11725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Molecular profile of ultrastructure changes of the ligamentum flavum related to lumbar spinal canal stenosis"],"prefix":"10.1002","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-1938","authenticated-orcid":false,"given":"Eliezer","family":"Sidon","sequence":"first","affiliation":[{"name":"Orthopedic Department Beilinson Hospital, Rabin Medical Center Petah Tikva Israel"},{"name":"Department of Cell and Developmental Biology Sackler School of Medicine, Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shai S.","family":"Shemesh","sequence":"additional","affiliation":[{"name":"Orthopedic Department Beilinson Hospital, Rabin Medical Center Petah Tikva Israel"},{"name":"Department of Cell and Developmental Biology Sackler School of Medicine, Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Mor\u2010Yossef Moldovan","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Sackler School of Medicine, Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yarden","family":"Wiesenfeld","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Sackler School of Medicine, Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nissim","family":"Ohana","sequence":"additional","affiliation":[{"name":"Orthopedic Department, Meir Medical Center Kfar Saba Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafna","family":"Benayahu","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Sackler School of Medicine, Tel Aviv University Tel Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,3]]},"reference":[{"key":"e_1_2_7_1_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e3181bfca15"},{"key":"e_1_2_7_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9290(68)90006-7"},{"key":"e_1_2_7_1_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000263407.25009.6e"},{"key":"e_1_2_7_1_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.brs.0000188117.77657.ee"},{"key":"e_1_2_7_1_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/BSD.0b013e3182698501"},{"key":"e_1_2_7_1_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/derm.22028"},{"key":"e_1_2_7_1_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010017\u20105315\u20100"},{"key":"e_1_2_7_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2013.01.003"},{"key":"e_1_2_7_1_10_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.46.11.1881"},{"key":"e_1_2_7_1_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports\u20102015\u2010094735"},{"key":"e_1_2_7_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2016.02.016"},{"key":"e_1_2_7_1_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010008\u20100662\u20105"},{"issue":"1","key":"e_1_2_7_1_14_1","first-page":"16","article-title":"Diabetes mellitus as a risk factor for the development of lumbar spinal stenosis","volume":"12","author":"Anekstein Y","year":"2010","journal-title":"Isr Med Assoc J"},{"key":"e_1_2_7_1_15_1","doi-asserted-by":"publisher","DOI":"10.4137\/CMED.S39035"},{"key":"e_1_2_7_1_16_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e31828a2517"},{"key":"e_1_2_7_1_17_1","doi-asserted-by":"publisher","DOI":"10.1021\/pr101065j"},{"key":"e_1_2_7_1_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3901"},{"key":"e_1_2_7_1_19_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.8.5707"},{"key":"e_1_2_7_1_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2005.02934.x"},{"key":"e_1_2_7_1_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20104658.2010.07797.x"},{"key":"e_1_2_7_1_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1297"},{"key":"e_1_2_7_1_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1215779110"},{"key":"e_1_2_7_1_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10735\u2010015\u20109645\u20100"},{"key":"e_1_2_7_1_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/wound.2013.0464"},{"key":"e_1_2_7_1_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1524\u2010475X.2011.00677.x"},{"key":"e_1_2_7_1_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072\u2010008\u20109113\u2010y"},{"key":"e_1_2_7_1_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582\u20104934.2012.01654.x"},{"key":"e_1_2_7_1_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ar.22694"},{"key":"e_1_2_7_1_30_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.07\u2010083857"},{"key":"e_1_2_7_1_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000000795"},{"key":"e_1_2_7_1_32_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00999"},{"key":"e_1_2_7_1_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.201400442"},{"key":"e_1_2_7_1_34_1","doi-asserted-by":"publisher","DOI":"10.1177\/0363546508331137"},{"key":"e_1_2_7_1_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296\u2010009\u20101001\u20109"},{"key":"e_1_2_7_1_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhsa.2013.03.049"},{"key":"e_1_2_7_1_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264\u2010015\u20102775\u2010x"},{"key":"e_1_2_7_1_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0119974"},{"key":"e_1_2_7_1_39_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046\u20103758.17.2000115"},{"key":"e_1_2_7_1_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncprheum0700"},{"key":"e_1_2_7_1_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0074942"},{"key":"e_1_2_7_1_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00536.2003"},{"key":"e_1_2_7_1_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00767.2012"},{"key":"e_1_2_7_1_44_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.E.00251"},{"key":"e_1_2_7_1_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00776\u2010011\u20100135\u20102"},{"key":"e_1_2_7_1_46_1","doi-asserted-by":"publisher","DOI":"10.3109\/03008207.2013.848199"},{"key":"e_1_2_7_1_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-200111010-00007"},{"key":"e_1_2_7_1_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2013.02.003"},{"key":"e_1_2_7_1_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0b013e3182116e39"},{"key":"e_1_2_7_1_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.05.007"},{"key":"e_1_2_7_1_51_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0000000000001226"}],"container-title":["Journal of Cellular Biochemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcb.28451","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.28451","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcb.28451","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcb.28451","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,13]],"date-time":"2025-04-13T18:15:36Z","timestamp":1744568136000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcb.28451"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3]]},"references-count":50,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2019,7]]}},"alternative-id":["10.1002\/jcb.28451"],"URL":"https:\/\/doi.org\/10.1002\/jcb.28451","archive":["Portico"],"relation":{},"ISSN":["0730-2312","1097-4644"],"issn-type":[{"value":"0730-2312","type":"print"},{"value":"1097-4644","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3]]},"assertion":[{"value":"2018-08-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}