PMID- 23335273
OWN - NLM
STAT- MEDLINE
DCOM- 20130618
LR  - 20161026
IS  - 1529-0131 (Electronic)
IS  - 0004-3591 (Linking)
VI  - 65
IP  - 5
DP  - 2013 May
TI  - Suppression of hyaluronan synthesis alleviates inflammatory responses in murine 
      arthritis and in human rheumatoid synovial fibroblasts.
PG  - 1160-70
LID - 10.1002/art.37861 [doi]
AB  - OBJECTIVE: To clarify the roles of hyaluronan (HA) in joint inflammation and the 
      process of joint destruction, using 4-methylumbelliferone (4-MU), an inhibitor of 
      HA synthesis, in a mouse model of collagen-induced arthritis (CIA) and in a 
      monolayer culture of fibroblast-like synoviocytes (FLS) derived from patients 
      with rheumatoid arthritis. METHODS: DAB/1J mice were immunized with type II 
      collagen. The effects of 4-MU were evaluated by the physiologic arthritis score, 
      paw swelling, the histologic arthritis score, and expression of matrix 
      metalloproteinase 3 (MMP-3) and MMP-13 in chondrocytes and synovial tissue. In 
      vitro, the effect of 4-MU on messenger RNA and protein expression of MMP-1 and 
      MMP-3 was determined. The effects of 4-MU on HA deposition and on serum/medium 
      concentrations of HA were analyzed using biotinylated HA binding protein staining 
      and an HA binding assay, respectively. RESULTS: Treatment with 4-MU in mice with 
      CIA dramatically decreased the severity of arthritis (based on the arthritis 
      score), paw thickness, and histopathologic changes. MMP-3 and MMP-13 expression 
      in chondrocytes and synovial cells was significantly inhibited by 4-MU in vivo. 
      Treatment with 4-MU also inhibited MMP-1 and MMP-3 expression in tumor necrosis 
      factor alpha-stimulated FLS, in a dose-dependent manner. The 4-MU-induced decreases 
      in the serum HA concentration in mice with CIA and in "medium" and "pericellular" 
      HA concentrations in cultured FLS support the contention that the inhibitory 
      mechanism of 4-MU is mediated by HA suppression. CONCLUSION: Reduced disease 
      activity induced by 4-MU in mice with CIA revealed HA to be a crucial regulator 
      in the course of arthritis. Therefore, 4-MU is a potential therapeutic agent in 
      arthritis, and its inhibitory mechanism is possibly mediated by suppression of HA 
      synthesis.
CI  - Copyright (c) 2013 by the American College of Rheumatology.
FAU - Yoshioka, Yutaka
AU  - Yoshioka Y
AD  - Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan.
FAU - Kozawa, Eiji
AU  - Kozawa E
FAU - Urakawa, Hiroshi
AU  - Urakawa H
FAU - Arai, Eisuke
AU  - Arai E
FAU - Futamura, Naohisa
AU  - Futamura N
FAU - Zhuo, Lisheng
AU  - Zhuo L
FAU - Kimata, Koji
AU  - Kimata K
FAU - Ishiguro, Naoki
AU  - Ishiguro N
FAU - Nishida, Yoshihiro
AU  - Nishida Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antirheumatic Agents)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 3T5NG4Q468 (Hymecromone)
RN  - 9004-61-9 (Hyaluronic Acid)
SB  - IM
CIN - J Biol Chem. 2016 Jun 3;291(23):12087-104. PMID: 27129266
MH  - Adjuvants, Immunologic/*antagonists & inhibitors/biosynthesis/blood
MH  - Administration, Oral
MH  - Animals
MH  - Antirheumatic Agents/pharmacology
MH  - Arthritis, Experimental/drug therapy/*metabolism/pathology
MH  - Arthritis, Rheumatoid/drug therapy/*metabolism/pathology
MH  - Cells, Cultured
MH  - Edema/chemically induced/drug therapy/pathology
MH  - Fibroblasts/drug effects/*metabolism/pathology
MH  - Gene Knockdown Techniques
MH  - Hindlimb/drug effects/pathology
MH  - Humans
MH  - Hyaluronic Acid/*antagonists & inhibitors/biosynthesis/blood
MH  - Hymecromone/analogs & derivatives/pharmacology
MH  - Mice
MH  - Mice, Inbred DBA
MH  - RNA, Messenger/antagonists & inhibitors/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Stifle/drug effects/pathology
MH  - Synovial Membrane/drug effects/*metabolism/pathology
EDAT- 2013/01/22 06:00
MHDA- 2013/06/19 06:00
CRDT- 2013/01/22 06:00
PHST- 2012/06/05 00:00 [received]
PHST- 2013/01/03 00:00 [accepted]
PHST- 2013/01/22 06:00 [entrez]
PHST- 2013/01/22 06:00 [pubmed]
PHST- 2013/06/19 06:00 [medline]
AID - 10.1002/art.37861 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2013 May;65(5):1160-70. doi: 10.1002/art.37861.