title: Osteoclast activators are elevated in intervertebral disks with Modic changes among patients operated for herniated nucleus pulposus.
abstract: OBJECTIVE
  Modic changes (MC) are associated with low back pain (LBP). Inflammation is considered as a key factor that triggers symptoms in especially type I MC, but so far of the potential inflammatory candidates only TNFα has been linked to MC. The objective of the study was to analyze a set of inflammatory mediators in human surgical disk samples and quantify their association with MC in the adjacent vertebral bodies.
  
  
  METHODS
  The study sample consisted of 51 intervertebral disk tissue specimens; 20 'No MC' disks, 19 'Type I MC' disks, and 12 'Type II MC' disks. mRNA expression of 46 cytokines was quantified from isolated RNA. Tissue samples were stained using hematoxylin and eosin, toluidine blue, Herovici, CD68 and CD163.
  
  
  RESULTS
  No significant differences were found in the amount of macrophages or presence of chondrocyte conglomerates between the MC groups. Of the multiple genes tested, statistically significant associations were observed for M-CSF1 (p = 0.028), RANKL (p = 0.035), RUNX1 (p = 0.032), and RUNX2 (p = 0.047) that were increased in 'Type II MC,' while OSCAR (p = 0.042) was increased in 'Type I MC' group compared to 'No MC.'
  
  
  CONCLUSIONS
  Since these cytokines are related to differentiation and proliferation of osteoclasts, our data suggest that the stimulation of vertebral osteoclasts by factors secreted by disk tissue is involved in the pathophysiology of MC.
authors: Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland.
authors: Matias
authors: M
authors: Torkki
authors: Unit of Systems Toxicology and Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland.
authors: Marja-Leena
authors: ML
authors: Majuri
authors: Unit of Systems Toxicology and Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland.
authors: Henrik
authors: H
authors: Wolff
authors: Department of Neurosurgery, Oulu University Hospital, Oulu, Finland.
authors: Tatu
authors: T
authors: Koskelainen
authors: Institute of Diagnostics, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors: Marianne
authors: M
authors: Haapea
authors: Institute of Diagnostics, Oulu University Hospital and University of Oulu, Oulu, Finland.
authors: Jaakko
authors: J
authors: Niinimäki
authors: Unit of Systems Toxicology and Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland.
authors: Harri
authors: H
authors: Alenius
authors: Department of Orthopaedic Surgery, University of California at San Francisco, San Francisco, CA, USA.
authors: Jeffrey
authors: J
authors: Lotz
authors: Centre of Expertise for Health and Work Ability, Occupational Health Services and Work Health, and Disability Prevention Centre, Finnish Institute of Occupational Health, Oulu, Finland. jaro.karppinen@ttl.fi.|Centre for Life Course Epidemiology and Systems Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, PL 5000, Oulu, 90014, Oulu, Finland. jaro.karppinen@ttl.fi.
authors: Jaro
authors: J
authors: Karppinen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D017586:Diskectomy; D005260:Female; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000601:surgery; D007405:Intervertebral Disc Displacement / Q000378:metabolism* / Q000601:surgery; D008159:Lumbar Vertebrae / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D010010:Osteoclasts / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines
keywords: Cytokine; Intervertebral disk; Modic changes; mRNA