title: 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.
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 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 ((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.
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: E H
authors.initials: EH
authors.lastname: Frank
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Chubinskaya
authors.forename: H-H
authors.initials: HH
authors.lastname: Huang
authors.forename: A J
authors.initials: AJ
authors.lastname: Grodzinsky
mesh_terms: D053674:Aggrecans / Q000187:drug effects / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D002358:Cartilage, Articular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000494:pharmacology*; D015536:Down-Regulation; D010450:Endopeptidases / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006025:Glycosaminoglycans / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000494:pharmacology*; D019947:Receptors, Interleukin-6 / Q000235:genetics; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D016207:Cytokines; D006025:Glycosaminoglycans; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C013786:A73025; D010450:Endopeptidases; C083641:aggrecanase
keywords: Apoptosis; Cartilage; Cytokines; Dynamic compression; Injury; Rehabilitation post-injury