PMID- 21679445
OWN - NLM
STAT- MEDLINE
DCOM- 20120313
LR  - 20211020
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 13
IP  - 3
DP  - 2011 Jun 16
TI  - Hyaluronan modulates accumulation of hypoxia-inducible factor-1 alpha, inducible 
      nitric oxide synthase, and matrix metalloproteinase-3 in the synovium of rat 
      adjuvant-induced arthritis model.
PG  - R90
LID - 10.1186/ar3365 [doi]
AB  - INTRODUCTION: Hypoxia is a feature of the inflamed synovium in rheumatoid 
      arthritis (RA). Intra-articular injection of hyaluronan (HA) may be considered a 
      potential way to treat RA. However, the exact molecular mechanism of HA on 
      decreased cellular responses to hypoxic environment is unclear. The present study 
      has been designed to use the adjuvant-induced arthritis model to examine the 
      effects of HA on the changes of immunohistochemical expressions of 
      hypoxia-inducible factor-1alpha (HIF-1alpha), inducible nitric oxide synthase 
      (iNOS), and matrix metalloproteinase-3 (MMP3) in the synovial tissues at the 
      early phase of arthritic inflammation. METHODS: Monoarthritis was induced in 
      adult male Sprague-Dawley (250-300 g) via intraarticular injection of complete 
      Freund's adjuvant (CFA) into the tibiotarsal joint. The CFA-induction arthritis 
      animals were divided into three groups: treatment (intraarticular injection of 
      HA), placebo (intraarticular injection of saline) and controls (no treatments). 
      Functional evaluations of edema and pain behavior, histology, and HIF-1alpha, 
      iNOS, and MMP3 immunohistochemistry were performed before, after the first 
      injection, three injections, and on the follow-up injection of the treatments. 
      RESULTS: Intra-articular injection of HA also significantly suppressed the 
      mechanical allodynia (p < 0.001) and overexpressions of HIF-1alpha (p < 0.001), 
      iNOS (p = 0.004) and MMP3 (p < 0.001) immunoreactivity in synovium. CONCLUSIONS: 
      This study demonstrated that early intervention of HA is an effective protection 
      against accumulation of inflammation-induced HIF-1alpha, iNOS, and MMP3 to limit 
      erosive damage in CFA-induced model of arthritis.
FAU - Chou, Li-Wei
AU  - Chou LW
AD  - Department of Physical Therapy, Graduate Institute of Rehabilitation Science, 
      China Medical University, 91 Hsueh-Shih Road, Taichung, Taiwan 40202, Republic of 
      China.
FAU - Wang, John
AU  - Wang J
FAU - Chang, Pei-Lin
AU  - Chang PL
FAU - Hsieh, Yueh-Ling
AU  - Hsieh YL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110616
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Viscosupplements)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - 9007-81-2 (Freund's Adjuvant)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
SB  - IM
MH  - Animals
MH  - Arthralgia/drug therapy/immunology/metabolism
MH  - Arthritis, Experimental/*drug therapy/immunology/metabolism
MH  - Edema/drug therapy/immunology/metabolism
MH  - Freund's Adjuvant/pharmacology
MH  - Hyaluronic Acid/*pharmacology
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Injections, Intra-Articular
MH  - Male
MH  - Matrix Metalloproteinase 3/*metabolism
MH  - Nitric Oxide Synthase Type II/*metabolism
MH  - Nociception/drug effects
MH  - Pain Threshold/drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Synovial Membrane/drug effects/immunology/metabolism
MH  - Viscosupplements/pharmacology
PMC - PMC3218905
EDAT- 2011/06/18 06:00
MHDA- 2012/03/14 06:00
PMCR- 2011/06/16
CRDT- 2011/06/18 06:00
PHST- 2011/02/10 00:00 [received]
PHST- 2011/03/20 00:00 [revised]
PHST- 2011/06/16 00:00 [accepted]
PHST- 2011/06/18 06:00 [entrez]
PHST- 2011/06/18 06:00 [pubmed]
PHST- 2012/03/14 06:00 [medline]
PHST- 2011/06/16 00:00 [pmc-release]
AID - ar3365 [pii]
AID - 10.1186/ar3365 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2011 Jun 16;13(3):R90. doi: 10.1186/ar3365.