PMID- 15751080
OWN - NLM
STAT- MEDLINE
DCOM- 20050505
LR  - 20181113
IS  - 0004-3591 (Print)
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 52
IP  - 3
DP  - 2005 Mar
TI  - Hyaluronan oligosaccharide-induced activation of transcription factors in bovine 
      articular chondrocytes.
PG  - 800-9
AB  - OBJECTIVE: To document the activity profile of transcription factors following 
      chondrocyte stimulation with hyaluronan (HA) hexasaccharides (HA(6)) and to 
      determine the expression of genes whose transcriptional activation is tightly 
      associated with the transcription factors. METHODS: Nuclear extracts from bovine 
      articular chondrocytes treated with HA(6) were subjected to transcription factor 
      protein-DNA array analysis. Electrophoretic mobility shift assay (EMSA) analyses 
      were performed to confirm the results of protein-DNA array. The gene expressions 
      of matrix metalloproteinase 3 (MMP-3), type II collagen, and cartilage oligomeric 
      matrix protein (COMP) were examined by quantitative real-time reverse 
      transcription-polymerase chain reaction (RT-PCR), and protease activity was 
      assessed by casein zymography. RESULTS: In the protein-DNA array analysis, 12 
      transcription factors were up-regulated and 2 transcription factors were 
      down-regulated in the chondrocytes treated with HA(6). The transcription factors 
      retinoic acid receptor (RAR), retinoid X receptor (RXR), and Sp-1 exhibited 
      >2-fold increased activity by HA(6) treatment, as confirmed by EMSA. RT-PCR 
      analysis showed that the expression levels of MMP-3, type II collagen, and COMP 
      messenger RNA, which are tightly associated with the activation of RAR, RXR, or 
      Sp-1, were up-regulated by treatment with HA(6). Addition of high molecular mass 
      HA after HA(6) treatment resulted in abrogation of the MMP-3 induction. 
      CONCLUSION: These results suggest that HA(6) increase the activity of multiple 
      transcription factors in chondrocytes and signal the enhanced expression of key 
      genes involved in cartilage-matrix remodeling and turnover. The data also 
      demonstrate that high molecular mass HA has a potential to suppress the signaling 
      activated by HA(6).
FAU - Ohno, Shigeru
AU  - Ohno S
AD  - Rush Medical College, Rush University Medical Center, Chicago, Illinois 60612, 
      USA.
FAU - Im, Hee-Jeong
AU  - Im HJ
FAU - Knudson, Cheryl B
AU  - Knudson CB
FAU - Knudson, Warren
AU  - Knudson W
LA  - eng
GR  - R01 AR043384/AR/NIAMS NIH HHS/United States
GR  - R01-AR-43384/AR/NIAMS NIH HHS/United States
GR  - P50-AR-39239/AR/NIAMS NIH HHS/United States
GR  - R01-AR-39507/AR/NIAMS NIH HHS/United States
GR  - P50 AR039239/AR/NIAMS NIH HHS/United States
GR  - I01 BX002647/BX/BLRD VA/United States
GR  - R01 AR053220-04/AR/NIAMS NIH HHS/United States
GR  - R01 AR039507/AR/NIAMS NIH HHS/United States
GR  - R01 AR053220/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 (Adjuvants, Immunologic)
RN  - 0 (Oligosaccharides)
RN  - 0 (Transcription Factors)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
MH  - Adjuvants, Immunologic/genetics/*pharmacology
MH  - Animals
MH  - Cartilage, Articular/*drug effects
MH  - Cattle
MH  - Chondrocytes/*drug effects
MH  - Gene Expression/drug effects/genetics
MH  - Hyaluronic Acid/genetics/*pharmacology
MH  - Microarray Analysis
MH  - Oligosaccharides/genetics/pharmacology
MH  - Signal Transduction
MH  - Transcription Factors/*drug effects/genetics
PMC - PMC2893143
MID - NIHMS211527
EDAT- 2005/03/08 09:00
MHDA- 2005/05/06 09:00
PMCR- 2010/06/28
CRDT- 2005/03/08 09:00
PHST- 2005/03/08 09:00 [pubmed]
PHST- 2005/05/06 09:00 [medline]
PHST- 2005/03/08 09:00 [entrez]
PHST- 2010/06/28 00:00 [pmc-release]
AID - 10.1002/art.20937 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2005 Mar;52(3):800-9. doi: 10.1002/art.20937.