Moderate dynamic compression inhibits pro-catabolic response of cartilage to mechanical injury, TNF-α and IL-6, but accentuates degradation above a strain threshold
Author(s)Li, Yang; Frank, Eliot; Wang, Yang; Chubinskaya, Susan; Huang, Han-Hwa; Grodzinsky, Alan J.; ... Show more Show less
Moderate dynamic compression inhibits pro-catabolic response of cartilage to mechanical injury, tumor necrosis factor-α and interleukin-6, but accentuates degradation above a strain threshold
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Objective Traumatic joint injury can initiate early cartilage degeneration in the presence of elevated inflammatory cytokines (e.g., tumor necrosis factor (TNF)-α and interleukin (IL)-6). The positive/negative effects of post-injury dynamic loading on cartilage degradation and repair in vivo are not well-understood. This study examined the effects of dynamic strain on immature bovine cartilage in vitro challenged with TNF-α + IL-6 and its soluble receptor (sIL-6R) with/without initial mechanical injury. Methods Groups of mechanically injured or non-injured explants were cultured in TNF-α + IL-6/sIL-6R for 8 days. Intermittent dynamic compression was applied concurrently at 10%, 20%, or 30% strain amplitude. Outcome measures included sulfated glycosaminoglycan (sGAG) loss (dimethylmethylene blue (DMMB)), aggrecan biosynthesis ([superscript 35]S-incorporation), aggrecanase activity (Western blot), chondrocyte viability (fluorescence staining) and apoptosis (nuclear blebbing via light microscopy), and gene expression (qPCR). Results In bovine explants, cytokine alone and injury-plus-cytokine treatments markedly increased sGAG loss and aggrecanase activity, and induced chondrocyte apoptosis. These effects were abolished by moderate 10% and 20% strains. However, 30% strain amplitude greatly increased apoptosis and had no inhibitory effect on aggrecanase activity. TNF + IL-6/sIL-6R downregulated matrix gene expression and upregulated expression of inflammatory genes, effects that were rescued by moderate dynamic strains but not by 30% strain. Conclusions Moderate dynamic compression inhibits the pro-catabolic response of cartilage to mechanical injury and cytokine challenge, but there is a threshold strain amplitude above which loading becomes detrimental to cartilage. Our findings support the concept of appropriate loading for post-injury rehabilitation.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering
Osteoarthritis and Cartilage
Li, Y., E.H. Frank, Y. Wang, S. Chubinskaya, H.-H. Huang, and A.J. Grodzinsky. “Moderate Dynamic Compression Inhibits Pro-Catabolic Response of Cartilage to Mechanical Injury, Tumor Necrosis Factor-α and Interleukin-6, but Accentuates Degradation Above a Strain Threshold.” Osteoarthritis and Cartilage 21, no. 12 (December 2013): 1933–1941.
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