MIT Libraries homeMIT Libraries logoDSpace@MIT

MIT
View Item 
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
  • DSpace@MIT Home
  • MIT Open Access Articles
  • MIT Open Access Articles
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

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
Thumbnail
DownloadGrodzinsky_Moderate dynamic.pdf (1.864Mb)
PUBLISHER_CC

Publisher with Creative Commons License

Creative Commons Attribution

Alternative 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
Terms of use
Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/4.0/
Metadata
Show full item record
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 ([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.
Date issued
2013-09
URI
http://hdl.handle.net/1721.1/99434
Department
Massachusetts Institute of Technology. Department of Biological Engineering
Journal
Osteoarthritis and Cartilage
Publisher
Elsevier
Citation
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.
Version: Author's final manuscript
ISSN
10634584
1522-9653

Collections
  • MIT Open Access Articles

Browse

All of DSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

My Account

Login

Statistics

OA StatisticsStatistics by CountryStatistics by Department
MIT Libraries homeMIT Libraries logo

Find us on

Twitter Facebook Instagram YouTube RSS

MIT Libraries navigation

SearchHours & locationsBorrow & requestResearch supportAbout us
PrivacyPermissionsAccessibility
MIT
Massachusetts Institute of Technology
Content created by the MIT Libraries, CC BY-NC unless otherwise noted. Notify us about copyright concerns.