{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T19:29:01Z","timestamp":1791660541517,"version":"4.3.4"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T00:00:00Z","timestamp":1515542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100002718","name":"Cervical Spine Research Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R03 AR066342"],"award-info":[{"award-number":["R03 AR066342"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01 AR049069"],"award-info":[{"award-number":["R01 AR049069"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1 TR000135"],"award-info":[{"award-number":["UL1 TR000135"]}],"id":[{"id":"10.13039\/100006108","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":[[2018,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:label\/><jats:p>Degenerative disk disease of the spine is a major cause of back pain and disability. Optimization of regenerative medical therapies for degenerative disk disease requires a deep mechanistic understanding of the factors controlling the structural integrity of spinal tissues. In this investigation, we sought to identify candidate regulatory genes controlling extracellular matrix synthesis in spinal tissues. To achieve this goal we performed high throughput next generation RNA sequencing on 39 annulus fibrosus and 21 nucleus pulposus human tissue samples. Specimens were collected from patients undergoing surgical discectomy for the treatment of degenerative disk disease. Our studies identified associations between extracellular matrix genes, growth factors, and other important regulatory molecules. The fibrous matrix characteristic of annulus fibrosus was associated with expression of the growth factors platelet derived growth factor beta (PDGFB), vascular endothelial growth factor C (VEGFC), and fibroblast growth factor 9 (FGF9). Additionally we observed high expression of multiple signaling proteins involved in the NOTCH and WNT signaling cascades. Nucleus pulposus extracellular matrix related genes were associated with the expression of numerous diffusible growth factors largely associated with the transforming growth signaling cascade, including transforming factor alpha (TGFA), inhibin alpha (INHA), inhibin beta A (INHBA), bone morphogenetic proteins (BMP2, BMP6), and others. Clinical significance: this investigation provides important data on extracellular matrix gene regulatory networks in disk tissues. This information can be used to optimize pharmacologic, stem cell, and tissue engineering strategies for regeneration of the intervertebral disk and the treatment of back pain. \u00a9 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1356\u20131369, 2018.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jor.23834","type":"journal-article","created":{"date-parts":[[2017,12,11]],"date-time":"2017-12-11T13:59:06Z","timestamp":1513000746000},"page":"1356-1369","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["RNA sequencing identifies gene regulatory networks controlling extracellular matrix synthesis in intervertebral disk tissues"],"prefix":"10.1002","volume":"36","author":[{"given":"Scott M.","family":"Riester","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"},{"name":"Department of Occupational and Environmental Medicine HealthPartners Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"},{"name":"Department of Orthopedic Surgery Tongji Medical College Huazhong University of Science and Technology Tongji Hospital Wuhan P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"},{"name":"Department of Orthopedic Surgery Tongji Medical College Huazhong University of Science and Technology Puai Hospital Wuhan P.R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Cong","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"},{"name":"Department of Orthopedic Surgery The First Hospital of China Medical University No.155, Nanjing Bei Street Shenyang 110001 P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel\u2010Moneim","family":"Mohamed Ali","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun H.","family":"Peck","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"},{"name":"Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lachlan J.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"},{"name":"Department of Orthopaedic Surgery Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford L.","family":"Currier","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Huddleston","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Krauss","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Yaszemski","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Morrey","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew P.","family":"Abdel","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Bydon","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchun","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Physical Medicine and Rehabilitation Mayo Clinic Rochester Minnesota"},{"name":"Division of Pain Medicine Department of Anesthesiology Mayo Clinic Rochester Minnesota"},{"name":"Spine Center Mayo Clinic Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalise N.","family":"Larson","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre J.","family":"van Wijnen","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Nassr","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery Mayo Clinic 200 First Street SW Rochester Minnesota 55905"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)60692-4"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2013-204631"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199503150-00011"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0300869"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.21513"},{"key":"e_1_2_7_7_1","first-page":"10","article-title":"Histology and pathology of the human intervertebral disc","volume":"88","author":"Roberts S","year":"2006","journal-title":"J Bone Joint Surg Am Vol"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199109000-00001"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2931"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2519"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.BRS.0000061986.03886.4F"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.24073"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00538.2006"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30342"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar4157"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2929"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/BRS.0b013e3181a55705"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1590\/S1415-47572013000300021"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.27710"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3892\/etm.2013.1421"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-013-0377-0"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2016.11.008"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-005-0954-y"},{"key":"e_1_2_7_24_1","first-page":"1911","article-title":"Reliability of new indices of radiographic osteoarthritis of the hand and hip and lumbar disc degeneration","volume":"20","author":"Lane NE","year":"1993","journal-title":"J Rheumatol"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2015.09.008"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.06.002"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-016-0370-8"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23209"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.672345"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2014.08.041"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-15-224"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-3-r25"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-4-r36"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu638"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/383627a0"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2005189"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.006403"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/014107688908200714"},{"key":"e_1_2_7_41_1","first-page":"43","article-title":"Identification of heterogeneous cell populations in normal human intervertebral disc","volume":"186","author":"Chelberg MK","year":"1995","journal-title":"J Anat"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08959"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.22789"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.298968"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586-007-0475-y"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.30607"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.20765"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjor.23834","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.23834","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T23:22:51Z","timestamp":1695511371000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.23834"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,1,10]]},"references-count":46,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1002\/jor.23834"],"URL":"https:\/\/doi.org\/10.1002\/jor.23834","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,1,10]]},"assertion":[{"value":"2017-03-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-12-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-01-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}