Moderate dynamic compression inhibits pro-catabolic response of cartilage to mechanical injury, TNF-α and IL-6, but accentuates degradation above a strain threshold

• Main Authors: Li, Yang (Contributor), Frank, Eliot (Contributor), Wang, Yang (Contributor), Chubinskaya, Susan (Author), Huang, Han-Hwa (Contributor), Grodzinsky, Alan J. (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Biological Engineering (Contributor)
• Format: Article
• Language: English
• Published: Elsevier, 2015-10-23T15:07:11Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institutes of Health (U.S.) (Grant AR060331)
National Institutes of Health (U.S.) (Grant AR045779)
National Institutes of Health (U.S.) (Biomechanics Training Grant Fellowship)