title: Characterization of degenerative human facet joints and facet joint capsular tissues.
abstract: OBJECTIVE
  Lumbar facet joint degeneration (FJD) may be an important cause of low back pain (LBP) and sciatica. The goal of this study was to characterize cellular alterations of inflammatory factor expression and neovascularization in human degenerative facet joint capsular (FJC) tissue. These alterations in FJC tissues in pain stimulation were also assessed.
  
  
  METHODS
  FJs were obtained from consented patients undergoing spinal reconstruction surgery and cadaveric donors with no history of back pain. Histological analyses of the FJs were performed. Cytokine antibody array and quantitative real-time polymerase chain reaction (qPCR) were used to determine the production of inflammatory cytokines, and western blotting analyses (WB) were used to assay for cartilage-degrading enzymes and pain mediators. Ex vivo rat dorsal root ganglion (DRG) co-culture with human FJC tissues was also performed.
  
  
  RESULTS
  Increased neovascularization, inflammatory cell infiltration, and pain-related axonal-promoting factors were observed in degenerative FJCs surgically obtained from symptomatic subjects. Increased VEGF, (NGF/TrkA), and sensory neuronal distribution were also detected in degenerative FJC tissues from subjects with LBP. qPCR and WB results demonstrated highly upregulated inflammatory cytokines, pain mediators, and cartilage-degrading enzymes in degenerative FJCs. Results from ex vivo co-culture of the DRG and FJC tissue demonstrated that degenerative FJCs increased the expression of inflammatory pain molecules in the sensory neurons.
  
  
  CONCLUSIONS
  Degenerative FJCs possess greatly increased inflammatory and angiogenic features, suggesting that these factors play an important role in the progression of FJD and serve as a link between joint degeneration and neurological stimulation of afferent pain fibers.
authors.affiliation: Department of Biochemistry, Rush University at Rush University Medical Center, Chicago, IL 60612, USA; The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju, 501-759, Republic of Korea. Electronic address: js_kim@chosun.ac.kr.
authors.forename: J-S
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Orthopedic Surgery, Rush University at Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: mali@rocsc.com.
authors.forename: M H
authors.initials: MH
authors.lastname: Ali
authors.affiliation: Department of Biochemistry, Rush University at Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: fwydra@gmail.com.
authors.forename: F
authors.initials: F
authors.lastname: Wydra
authors.affiliation: Department of Biochemistry, Rush University at Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: Xin_Li@rush.edu.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Rush University at Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: John_L_Hamilton@rush.edu.
authors.forename: J L
authors.initials: JL
authors.lastname: Hamilton
authors.affiliation: Department of Orthopedic Surgery, Rush University at Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: Howard_An@rush.edu.
authors.forename: H S
authors.initials: HS
authors.lastname: An
authors.affiliation: Department of Biochemistry, Rush University at Rush University Medical Center, Chicago, IL 60612, USA; Department of Orthopedic Surgery, Rush University at Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: Gabriella_Cs-Szabo@rush.edu.
authors.forename: G
authors.initials: G
authors.lastname: Cs-Szabo
authors.affiliation: Array BioPharma, Boulder, CO 80301, USA. Electronic address: Steve.Andrews@arraybiopharma.com.
authors.forename: S
authors.initials: S
authors.lastname: Andrews
authors.affiliation: Department of Anesthesiology, Rush University at Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: Mario_Moric@rush.edu.
authors.forename: M
authors.initials: M
authors.lastname: Moric
authors.affiliation: Department of Biochemistry, Rush University at Rush University Medical Center, Chicago, IL 60612, USA; Department of Biology and Shenzhen Key Laboratory of Cell Microenvironment, South University of Science and Technology of China, Shenzhen 518055, China. Electronic address: Guozhi_Xiao@rush.edu.
authors.forename: G
authors.initials: G
authors.lastname: Xiao
authors.affiliation: MechanoBiology Laboratory Departments of Orthopaedic Surgery, Bioengineering, and Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: Wanghc@pitt.edu.
authors.forename: J H-C
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, Rush University at Rush University Medical Center, Chicago, IL 60612, USA. Electronic address: Di_Chen@rush.edu.
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.affiliation: Bioengineering Center, Wayne State University, Detroit, MI 48202, USA. Electronic address: jmc@wayne.edu.
authors.forename: J M
authors.initials: JM
authors.lastname: Cavanaugh
authors.affiliation: Department of Biochemistry, Rush University at Rush University Medical Center, Chicago, IL 60612, USA; Department of Orthopedic Surgery, Rush University at Rush University Medical Center, Chicago, IL 60612, USA; Department of Internal Medicine, Section of Rheumatology, Rush University at Rush University Medical Center, Chicago, IL 60612, USA; Department of Bioengineering, University of Illinois, Chicago, IL 60612, USA; Jesse Brown Veterans Affair, Chicago, IL 60612, USA. Electronic address: Hee-Jeong_Sampen@rush.edu.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Im
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015153:Blotting, Western; D002102:Cadaver; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal; D006801:Humans; D007150:Immunohistochemistry; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017746:Joint Capsule / Q000276:immunology / Q000378:metabolism*; D017116:Low Back Pain / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D008159:Lumbar Vertebrae; D008297:Male; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000378:metabolism; D055013:Osteoarthritis, Spine / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020917:Receptor, trkA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012600:Scoliosis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D013168:Spondylolisthesis / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult; D021801:Zygapophyseal Joint / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; C502240:NGF protein, human; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020932:Nerve Growth Factor; D020917:Receptor, trkA
keywords: Angiogenesis; Human facet joint capsular tissue; Inflammatory cytokines; Inflammatory pain mediators; Low back pain; Nerve ingrowth