Expression of interleukin-6 in osteoarthritic chondrocytes and effects of fluid-induced shear on this expression in normal human chondrocytes in vitro.
This study tested the effect of fluid-induced shear on interleukin-6 expression in normal human articular chondrocytes in vitro. As determined by Northern blot analysis, interleukin-6 mRNA expression occurs in chondrocytes from osteoarthritic cartilage but not in normal chondrocytes. Applying fluid-induced shear stress to primary high density cultures of chondrocytes increased interleukin-6 mRNA signal 4-fold at 1 hour and 10 to 15-fold at 48 hours compared with unsheared control cultures. At 48 hours, fluid-induced shear stress increased interleukin-6 protein levels in the culture medium 9 to 10-fold compared with unsheared controls. mRNA signals for interleukin-1alpha, interleukin-1beta, and tumor necrosis factor-alpha in RNA from sheared or control chondrocytes were not detected by Northern blotting. Transforming growth factor-beta mRNA signal was detectable but was not affected by shear. In contrast, human lung fibroblasts (WI-38) responded to fluid-induced shear with increased signal for transforming growth factor-beta, but not interleukin-6, mRNA. Both cell types did respond to interleukin-1alpha with increased interleukin-6 mRNA signal. These data demonstrated that distortional forces, such as fluid-induced shear stress, alter interleukin-6 levels in normal chondrocytes in vitro and suggest that increased interleukin-6 expression in osteoarthritic cartilage may result, in part, from alterations in the mechanical loading of the tissue.
Mohtai
M
M
Department of Functional Restoration, Veterans Affairs Medical Center, Palo Alto, CA, USA.
Gupta
M K
MK
Donlon
B
B
Ellison
B
B
Cooke
J
J
Gibbons
G
G
Schurman
D J
DJ
Smith
R L
RL
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000166:cytology; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D013314:Stress, Mechanical; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha