PMID- 20462435
OWN - NLM
STAT- MEDLINE
DCOM- 20101124
LR  - 20240516
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 12
IP  - 3
DP  - 2010
TI  - Biomechanical modulation of collagen fragment-induced anabolic and catabolic 
      activities in chondrocyte/agarose constructs.
PG  - R82
LID - 10.1186/ar3009 [doi]
AB  - INTRODUCTION: The present study examined the effect of collagen fragments on 
      anabolic and catabolic activities by chondrocyte/agarose constructs subjected to 
      dynamic compression. METHODS: Constructs were cultured under free-swelling 
      conditions or subjected to continuous and intermittent compression regimes, in 
      the presence of the N-terminal (NT) and C-terminal (CT) telopeptides derived from 
      collagen type II and/or 1400 W (inhibits inducible nitric oxide synthase (iNOS)). 
      The anabolic and catabolic activities were compared to the amino-terminal 
      fibronectin fragment (NH2-FN-f) and assessed as follows: nitric oxide (NO) 
      release and sulphated glycosaminoglycan (sGAG) content were quantified using 
      biochemical assays. Tumour necrosis factor-alpha (TNFalpha) and interleukin-1beta 
      (IL-1beta) release were measured by ELISA. Gene expression of matrix 
      metalloproteinase-3 (MMP-3), matrix metalloproteinase-13 (MMP-13), collagen type 
      II and fibronectin were assessed by real-time quantitative polymerase chain 
      reaction (qPCR). Two-way ANOVA and the post hoc Bonferroni-corrected t-test was 
      used to examine data. RESULTS: The presence of the NT or CT peptides caused a 
      moderate to strong dose-dependent stimulation of NO, TNFalpha and IL-1beta 
      production and inhibition of sGAG content. In some instances, high concentrations 
      of telopeptides were just as potent in stimulating catabolic activities when 
      compared to NH2-FN-f. Depending on the concentration and type of fragment, the 
      increased levels of NO and cytokines were inhibited with 1400 W, resulting in the 
      restoration of sGAG content. Depending on the duration and type of compression 
      regime employed, stimulation with compression or incubation with 1400 W or a 
      combination of both, inhibited telopeptide or NH2-FN-f induced NO release and 
      cytokine production and enhanced sGAG content. All fragments induced MMP-3 and 
      MMP-13 expression in a time-dependent manner. This effect was reversed with 
      compression and/or 1400 W resulting in the restoration of sGAG content and 
      induction of collagen type II and fibronectin expression. CONCLUSIONS: Collagen 
      fragments containing the N- and C-terminal telopeptides have dose-dependent 
      catabolic activities similar to fibronectin fragments and increase the production 
      of NO, cytokines and MMPs. Catabolic activities were downregulated by dynamic 
      compression or by the presence of the iNOS inhibitor, linking reparative 
      activities by both types of stimuli. Future investigations which examine the 
      signalling cascades of chondrocytes in response to matrix fragments with 
      mechanical influences may provide useful information for early osteoarthritis 
      treatments.
FAU - Chowdhury, Tina T
AU  - Chowdhury TT
AD  - School of Engineering and Materials Science, Queen Mary University of London, 
      Mile End Road, London, E1 4NS, UK. t.t.chowdhury@qmul.ac.uk
FAU - Schulz, Ronny M
AU  - Schulz RM
FAU - Rai, Sonpreet S
AU  - Rai SS
FAU - Thuemmler, Christian B
AU  - Thuemmler CB
FAU - Wuestneck, Nico
AU  - Wuestneck N
FAU - Bader, Augustinus
AU  - Bader A
FAU - Homandberg, Gene A
AU  - Homandberg GA
LA  - eng
GR  - G0502256/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100512
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type II)
RN  - 0 (Fibronectins)
RN  - 0 (Glycosaminoglycans)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (collagen type I trimeric cross-linked peptide)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9012-36-6 (Sepharose)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
CIN - Arthritis Res Ther. 2010;12(3):404. PMID: 20609261
MH  - Animals
MH  - Biomechanical Phenomena
MH  - Cells, Cultured
MH  - Chondrocytes/cytology/*drug effects/*metabolism
MH  - Collagen Type I/*pharmacology
MH  - Collagen Type II/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Fibronectins/metabolism
MH  - Glycosaminoglycans/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Metabolism/drug effects
MH  - Nitric Oxide/metabolism
MH  - Peptide Fragments/*pharmacology
MH  - Peptides/*pharmacology
MH  - *Sepharose
MH  - Swine
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC2911866
EDAT- 2010/05/14 06:00
MHDA- 2010/12/14 06:00
PMCR- 2010/05/12
CRDT- 2010/05/14 06:00
PHST- 2009/10/20 00:00 [received]
PHST- 2010/01/26 00:00 [revised]
PHST- 2010/05/12 00:00 [accepted]
PHST- 2010/05/14 06:00 [entrez]
PHST- 2010/05/14 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2010/05/12 00:00 [pmc-release]
AID - ar3009 [pii]
AID - 10.1186/ar3009 [doi]
PST - ppublish
SO  - Arthritis Res Ther. 2010;12(3):R82. doi: 10.1186/ar3009. Epub 2010 May 12.