Matias Torkki1, Marja-Leena Majuri2, Henrik Wolff2, Tatu Koskelainen3, Marianne Haapea4, Jaakko Niinimäki4, Harri Alenius2, Jeffrey Lotz5, Jaro Karppinen6,7. 1. Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland. 2. Unit of Systems Toxicology and Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland. 3. Department of Neurosurgery, Oulu University Hospital, Oulu, Finland. 4. Institute of Diagnostics, Oulu University Hospital and University of Oulu, Oulu, Finland. 5. Department of Orthopaedic Surgery, University of California at San Francisco, San Francisco, CA, USA. 6. 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. 7. 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.
Abstract
PURPOSE: 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.
PURPOSE: 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.
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