PMID- 22018973
OWN - NLM
STAT- MEDLINE
DCOM- 20120605
LR  - 20220309
IS  - 1872-6623 (Electronic)
IS  - 0304-3959 (Linking)
VI  - 153
IP  - 1
DP  - 2012 Jan
TI  - Suppression of pain and joint destruction by inhibition of the proteasome system 
      in experimental osteoarthritis.
PG  - 18-26
LID - 10.1016/j.pain.2011.08.001 [doi]
AB  - Osteoarthritis is a degenerative joint disease with pain and loss of joint 
      function as major pathological features. Recent studies show that proteasome 
      inhibitors reduce pain in various pathological conditions. We evaluated the 
      effects of MG132, a reversible proteasome inhibitor on pain and joint destruction 
      in a rat model of osteoarthritis. Osteoarthritis was induced by intraarticular 
      injection of monosodium iodoacetate into the rat knee. Knee joint stiffness was 
      scored and nociception was evaluated by mechanical pressure applied to the 
      respective hind paw. Knee joint destruction was assessed by radiological and 
      histological analyses. Expression of matrix metalloproteinase-3 (MMP-3) was 
      analyzed by quantitative reverse transcription polymerase chain reaction in the 
      knee articular cartilage. Expression of substance P (SP) and calcitonin 
      gene-related peptide (CGRP) was studied in the dorsal root ganglia (L4-L6) by 
      quantitative reverse transcription polymerase chain reaction and in the knee 
      joints by immunohistochemistry. Our results indicate that daily treatment of 
      osteoarthritic rats with MG132 significantly increases their mobility while the 
      swelling, pain thresholds, and pathological features of the affected joints were 
      reduced. Furthermore, the upregulated expression of MMP-3, SP, and CGRP in the 
      arthritic rats was normalized by MG132 administration. We conclude that the 
      proteasome inhibitor MG132 reduces pain and joint destruction, probably by 
      involving the peripheral nervous system, and that changes in SP and CGRP 
      expression correlate with alterations in behavioural responses. Our findings 
      suggest that nontoxic proteasome inhibitors may represent a novel pharmacotherapy 
      for osteoarthritis.
CI  - Copyright (c) 2011 International Association for the Study of Pain. Published by 
      Elsevier B.V. All rights reserved.
FAU - Ahmed, Aisha Siddiqah
AU  - Ahmed AS
AD  - Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska 
      University Hospital, Solna, Stockholm 17176, Sweden Department of Medicine, 
      Centre for Molecular Medicine, Karolinska Institutet, Karolinska University 
      Hospital, Solna, Stockholm 17176, Sweden Department of Clinical Sciences, 
      Danderyd Hospital, Karolinska Institutet, Stockholm 18288, Sweden Department of 
      Pharmaceutical Biosciences, Uppsala University, Uppsala 75105, Sweden Department 
      of Neurobiology, Care Sciences and Society, Center for Family and Community 
      Medicine, Karolinska Institutet, Huddinge 14183, Sweden.
FAU - Li, Jian
AU  - Li J
FAU - Erlandsson-Harris, Helena
AU  - Erlandsson-Harris H
FAU - Stark, Andre
AU  - Stark A
FAU - Bakalkin, Georgy
AU  - Bakalkin G
FAU - Ahmed, Mahmood
AU  - Ahmed M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111022
PL  - United States
TA  - Pain
JT  - Pain
JID - 7508686
RN  - 0 (Cysteine Proteinase Inhibitors)
RN  - 0 (Leupeptins)
RN  - 33507-63-0 (Substance P)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - JHB2QIZ69Z (Calcitonin Gene-Related Peptide)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*drug therapy/metabolism/pathology
MH  - Calcitonin Gene-Related Peptide/metabolism
MH  - Cartilage, Articular/drug effects/metabolism/pathology
MH  - Cysteine Proteinase Inhibitors/pharmacology/*therapeutic use
MH  - Female
MH  - Ganglia, Spinal/drug effects/metabolism
MH  - Knee Joint/*drug effects/metabolism/pathology
MH  - Leupeptins/pharmacology/*therapeutic use
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Osteoarthritis/*drug therapy/metabolism/pathology
MH  - Pain/*drug therapy/metabolism/pathology
MH  - Pain Measurement
MH  - Rats
MH  - Rats, Inbred Lew
MH  - Substance P/metabolism
EDAT- 2011/10/25 06:00
MHDA- 2012/06/06 06:00
CRDT- 2011/10/25 06:00
PHST- 2010/12/06 00:00 [received]
PHST- 2011/06/30 00:00 [revised]
PHST- 2011/08/01 00:00 [accepted]
PHST- 2011/10/25 06:00 [entrez]
PHST- 2011/10/25 06:00 [pubmed]
PHST- 2012/06/06 06:00 [medline]
AID - 00006396-201201000-00008 [pii]
AID - 10.1016/j.pain.2011.08.001 [doi]
PST - ppublish
SO  - Pain. 2012 Jan;153(1):18-26. doi: 10.1016/j.pain.2011.08.001. Epub 2011 Oct 22.