PMID- 12746902
OWN - NLM
STAT- MEDLINE
DCOM- 20030530
LR  - 20141120
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 48
IP  - 5
DP  - 2003 May
TI  - Proteoglycan degradation after injurious compression of bovine and human 
      articular cartilage in vitro: interaction with exogenous cytokines.
PG  - 1292-301
AB  - OBJECTIVE: Traumatic joint injury leads to an increased risk of osteoarthritis 
      (OA), but the progression to OA is not well understood. We undertook this study 
      to measure aspects of proteoglycan (PG) degradation after in vitro injurious 
      mechanical compression, including up-regulation of enzymatic degradative 
      expression and cytokine-stimulated degradation. METHODS: Articular cartilage 
      tissue explants were obtained from newborn bovine femoropatellar groove and from 
      adult normal human donor knee and ankle tissue. Following injurious compression 
      of the cartilage, matrix metalloproteinase 3 (MMP-3) and MMP-13 messenger RNA 
      (mRNA) expression levels were measured by Northern analysis, and PG loss to the 
      medium after cartilage injury was measured in the presence and absence of added 
      exogenous cytokine (interleukin-1alpha [IL-1alpha] or tumor necrosis factor alpha 
      [TNFalpha]). RESULTS: During the first 24 hours after injury in bovine cartilage, 
      MMP-3 mRNA levels increased 10-fold over the levels in control cartilage (n = 3 
      experiments), whereas MMP-13 mRNA levels were unchanged. PG loss was 
      significantly increased after injury, but only by 2% of the total PG content and 
      only for the first 3 days following injury. However, compared with injury alone 
      or cytokine treatment alone, treatment of injured tissue with either 1 ng/ml 
      IL-1alpha or 100 ng/ml TNFalpha caused marked increases in PG loss (35% and 54%, 
      respectively, of the total cartilage PG content). These interactions between 
      cytokine treatment and injury were statistically significant. In human knee 
      cartilage, the interaction was also significant for both IL-1alpha and TNFalpha, 
      although the magnitude of increase in PG loss was lower than that in bovine 
      cartilage. In contrast, in human ankle cartilage, there was no significant 
      interaction between injury and IL-1alpha. CONCLUSION: The cytokines IL-1alpha and 
      TNFalpha can cause a synergistic loss of PG from mechanically injured bovine and 
      human cartilage. By attempting to incorporate interactions with other joint 
      tissues that may be sources of cytokines, in vitro models of mechanical cartilage 
      injury may explain aspects of the interactions between mechanical forces and 
      degradative pathways which lead to OA progression.
FAU - Patwari, Parth
AU  - Patwari P
AD  - Center for Biomedical Engineering, Massachusetts Institute of Technology, 
      Cambridge, Massachusetts 02139, USA. pkp@mit.edu
FAU - Cook, Michael N
AU  - Cook MN
FAU - DiMicco, Michael A
AU  - DiMicco MA
FAU - Blake, Simon M
AU  - Blake SM
FAU - James, Ian E
AU  - James IE
FAU - Kumar, Sanjay
AU  - Kumar S
FAU - Cole, Ada A
AU  - Cole AA
FAU - Lark, Michael W
AU  - Lark MW
FAU - Grodzinsky, Alan J
AU  - Grodzinsky AJ
LA  - eng
GR  - AR-2P50-39239/AR/NIAMS NIH HHS/United States
GR  - AR-45779/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-1)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (Proteoglycans)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Adult
MH  - Animals
MH  - Animals, Newborn
MH  - Ankle Joint
MH  - Cartilage, Articular/drug effects/injuries/*metabolism
MH  - Cattle
MH  - Collagenases/genetics/metabolism
MH  - Culture Media, Conditioned/chemistry
MH  - Cycloheximide/pharmacology
MH  - Humans
MH  - In Vitro Techniques
MH  - Interleukin-1/*pharmacology
MH  - Knee Joint
MH  - Matrix Metalloproteinase 13
MH  - Matrix Metalloproteinase 3/genetics/metabolism
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Proteoglycans/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Stress, Mechanical
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Up-Regulation
EDAT- 2003/05/15 05:00
MHDA- 2003/05/31 05:00
CRDT- 2003/05/15 05:00
PHST- 2003/05/15 05:00 [pubmed]
PHST- 2003/05/31 05:00 [medline]
PHST- 2003/05/15 05:00 [entrez]
AID - 10.1002/art.10892 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2003 May;48(5):1292-301. doi: 10.1002/art.10892.