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.
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 bovinecartilage 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: Jonathan B Fitzgerald; Moonsoo Jin; Diana H Chai; Patrick Siparsky; Paul Fanning; Alan J Grodzinsky Journal: J Biol Chem Date: 2007-12-17 Impact factor: 5.157
Authors: Micky D Tortorella; Elizabeth C Arner; Robert Hills; Jennifer Gormley; Kam Fok; Lyle Pegg; Grace Munie; Anne-Marie Malfait Journal: Arch Biochem Biophys Date: 2005-10-26 Impact factor: 4.013
Authors: Kyle D Jadin; Benjamin L Wong; Won C Bae; Kelvin W Li; Amanda K Williamson; Barbara L Schumacher; Jeffrey H Price; Robert L Sah Journal: J Histochem Cytochem Date: 2005-05-06 Impact factor: 2.479
Authors: A M Loening; I E James; M E Levenston; A M Badger; E H Frank; B Kurz; M E Nuttall; H H Hung; S M Blake; A J Grodzinsky; M W Lark Journal: Arch Biochem Biophys Date: 2000-09-15 Impact factor: 4.013
Authors: Whasil Lee; Holly A Leddy; Yong Chen; Suk Hee Lee; Nicole A Zelenski; Amy L McNulty; Jason Wu; Kellie N Beicker; Jeffrey Coles; Stefan Zauscher; Jörg Grandl; Frederick Sachs; Farshid Guilak; Wolfgang B Liedtke Journal: Proc Natl Acad Sci U S A Date: 2014-11-10 Impact factor: 11.205
Authors: Robert L Trevino; Carol A Pacione; Anne-Marie Malfait; Susan Chubinskaya; Markus A Wimmer Journal: Cartilage Date: 2016-12-12 Impact factor: 4.634