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

Y. Li, E. H. Frank, Y. Wang, S. Chubinskaya, H. H. Huang, A. J. Grodzinsky

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

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 invivo are not well-understood. This study examined the effects of dynamic strain on immature bovine cartilage invitro 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 (35S-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.

Original languageEnglish (US)
Pages (from-to)1933-1941
Number of pages9
JournalOsteoarthritis and Cartilage
Volume21
Issue number12
DOIs
StatePublished - Dec 2013
Externally publishedYes

Keywords

  • Apoptosis
  • Cartilage
  • Cytokines
  • Dynamic compression
  • Injury
  • Rehabilitation post-injury

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

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