@article{f78c16d159d04a7cb05c6f458faf18c7,
title = "RNA sequencing identifies gene regulatory networks controlling extracellular matrix synthesis in intervertebral disk tissues",
abstract = "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.",
keywords = "RNA sequencing, annulus fibrosus, extracellular matrix, intervertebral disk, nucleus pulposus",
author = "Riester, {Scott M.} and Yang Lin and Wei Wang and Lin Cong and {Mohamed Ali}, {Abdel Moneim} and Peck, {Sun H.} and Smith, {Lachlan J.} and Currier, {Bradford L.} and Michelle Clark and Paul Huddleston and William Krauss and Yaszemski, {Michael J.} and Morrey, {Mark E.} and Abdel, {Matthew P.} and Mohamad Bydon and Wenchun Qu and Larson, {Annalise N.} and {van Wijnen}, {Andre J.} and Ahmad Nassr",
note = "Funding Information: Conflicts of interest: None. Grant sponsor: Cervical Spine Research Society 21st Century grant; Grant sponsor: National Institutes of Health; Grant sponsor: National Institute of Arthritis and Musculoskeletal and Skin Diseases NIAMS; Grant numbers: R03 AR066342, R01 AR049069; Grant sponsor: The National Center for Advancing Translational Sciences (NCATS); Grant number: UL1 TR000135; Grant sponsor: Doctor Research Startup Fund{\textquoteright} of Liaoning Province; Grant number: 201601114. Correspondence to: Andre J. van Wijnen and Ahmad Nassr (T: +507-538-0514; F: +507-284-5075; E-mail: vanwijnen.-andre@mayo.edu (A.J.W.); ahmad@mayo.edu (A.N.)) Funding Information: This publication was made possible by grants from the Cervical Spine Research Society (21st Century grant; to AN) and the generous philanthropic support of William and Karen Eby. Additional support was provided by the National Institutes of Health, including the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS, R03 AR066342, to ANL; R01 AR049069, to AJW) and the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (CTSA Grant Number UL1 TR000135, to ANL). Funding was also provided by the Mayo Graduate School (to SMR) through CTSA Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences. Additional support was also provided by the Doctor Research Startup Fund{\textquoteright} of Liaoning Province (Grant#201601114; to LC). We also thank the members of our research groups, including Emily Camilleri and Amel Dudakovic for stimulating discussions, as well as the Mayo Clinic Bioinformatics Core, including Jared Evans and Asha Nair for their assistance with high-throughput RNA sequencing and bioin-formatics support. Dr. Bradford Currier owns stock in Spinology and Tenex, and is on the Board of Directors for the Lumbar Spine Research Society. The remaining authors have no conflicts relevant to this publication. Funding Information: This publication was made possible by grants from the Cervical Spine Research Society (21st Century grant; to AN) and the generous philanthropic support of William and Karen Eby. Additional support was provided by the National Institutes of Health, including the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS, R03 AR066342, to ANL; R01 AR049069, to AJW) and the National Center for Advancing Translational Sciences (NCATS), a component of the National Institutes of Health (CTSA Grant Number UL1 TR000135, to ANL). Funding was also provided by the Mayo Graduate School (to SMR) through CTSA Grant Number UL1 TR000135 from the National Center for Advancing Translational Sciences. Additional support was also provided by the Doctor Research Startup Fund? of Liaoning Province (Grant#201601114; to LC). We also thank the members of our research groups, including Emily Camilleri and Amel Dudakovic for stimulating discussions, as well as the Mayo Clinic Bioinformatics Core, including Jared Evans and Asha Nair for their assistance with high-throughput RNA sequencing and bioinformatics support. Dr. Bradford Currier owns stock in Spinology and Tenex, and is on the Board of Directors for the Lumbar Spine Research Society. The remaining authors have no conflicts relevant to this publication. Publisher Copyright: {\textcopyright} 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.",
year = "2018",
month = may,
doi = "10.1002/jor.23834",
language = "English (US)",
volume = "36",
pages = "1356--1369",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "5",
}