title: Evaluation of 12 Novel Molecular Markers for Degenerated Nucleus Pulposus in a Chinese Population.
abstract: METHODS
  A transcriptional expression assessment of human samples.
  
  
  OBJECTIVE
  To evaluate 12 new candidate nucleus pulposus (NP) markers in degenerative disc disease in a Chinese population.
  
  
  BACKGROUND
  Disc degeneration is a major contributor of low back pain. However, no specific and reliable markers of degeneration of NP are available.
  
  
  METHODS
  Specimens of NP were collected from 81 patients and grouped into the degenerated disc group (undergoing discectomy and fusion with significant signs of disc degeneration) and the trauma control group (undergoing anterior vertebral body and disc excision and fusion without signs of disc degeneration). Lumbar spine magnetic resonance imaging, hematoxylin-eosin staining, and safranin O staining of sections of NP tissues were conducted to evaluate the severity of the disc degeneration in all samples. Quantitative reverse transcription polymerase chain reaction was performed to investigate the levels of mRNA expression of these genes, as well as those of aggrecan, type II collagen, and SRY-box 9 (SOX-9). Degenerated samples were also divided into groups according to Pfirrmann grading system to elucidate the association of severity of degeneration and gene transcriptional levels. We also tested the relationship between mRNA levels of these genes and clinical characteristics such as hypertension and diabetes mellitus.
  
  
  RESULTS
  We demonstrated that 11 of the 12 candidates showed significant differential expression in degenerated discs. Changes in the expression of these 11 genes were determined to be risk factors in degenerative disc diseases. The expression of neurochondrin (NCDN), keratin 8 (KRT8), and matrix Gla protein (MGP) even showed significant changes among subgroups of patients with degenerative disc disease stratified according to the Pfirrmann grading system. The expression of keratin 18 (KRT18), cadherin 2 (CDH2), synaptosomal-associated protein 25 (SNAP25), KRT8, and NCDN was significantly decreased in patients with hypertension. In contrast, the expression of MGP and cartilage oligomeric matrix protein was significantly upregulated in patients with diabetes mellitus.
  
  
  CONCLUSIONS
  Overall, we demonstrated the clinical utility of 11 novel NP markers for degenerative disc disease. Among them, the expression of NCDN, KRT8, and MGP may indicate the severity of disc degeneration.
  
  
  METHODS
  N/A.
authors.affiliation: *Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Zhejiang, China †Key Laboratory of Biotherapy of Zhejiang Province, Hangzhou, China; and ‡Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Hu
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Zhou
authors.forename: Xian-Feng
authors.initials: XF
authors.lastname: Lin
authors.forename: Feng-Dong
authors.initials: FD
authors.lastname: Zhao
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Ma
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Zhang
authors.forename: Ji-Ying
authors.initials: JY
authors.lastname: Wang
authors.forename: An
authors.initials: A
authors.lastname: Qin
authors.forename: Shun-Wu
authors.initials: SW
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D015415:Biomarkers; D015820:Cadherins / Q000235:genetics; D002135:Calcium-Binding Proteins / Q000235:genetics; D064236:Cartilage Oligomeric Matrix Protein / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D003920:Diabetes Mellitus / Q000235:genetics; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000235:genetics; D055959:Intervertebral Disc Degeneration / Q000235:genetics* / Q000473:pathology; D053538:Keratin-18 / Q000235:genetics; D053539:Keratin-19 / Q000235:genetics; D053533:Keratin-8 / Q000235:genetics; D008159:Lumbar Vertebrae; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D039942:Neuropilin-1 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012720:Severity of Illness Index; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics; D014158:Transcription, Genetic; D000097568:Matrix Gla Protein
chemical_list: D015415:Biomarkers; D015820:Cadherins; D002135:Calcium-Binding Proteins; D064236:Cartilage Oligomeric Matrix Protein; D016326:Extracellular Matrix Proteins; D053538:Keratin-18; D053539:Keratin-19; D053533:Keratin-8; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039942:Neuropilin-1; D012333:RNA, Messenger; D011991:Receptors, Virus; D012097:Repressor Proteins; D050825:Synaptosomal-Associated Protein 25; D000097568:Matrix Gla Protein; C104089:BASP1 protein, human; C119189:neurochondrin; C066100:poliovirus receptor