PMID- 16427328
OWN - NLM
STAT- MEDLINE
DCOM- 20061017
LR  - 20181201
IS  - 1063-4584 (Print)
IS  - 1063-4584 (Linking)
VI  - 14
IP  - 5
DP  - 2006 May
TI  - Peroxynitrite-modified collagen-II induces p38/ERK and NF-kappaB-dependent 
      synthesis of prostaglandin E2 and nitric oxide in chondrogenically differentiated 
      mesenchymal progenitor cells.
PG  - 460-70
AB  - OBJECTIVE: Peroxynitrite (ONOO(-)) is formed in the inflamed and degenerating 
      human joint. Peroxynitrite-modified collagen-II (PMC-II) was recently discovered 
      in the serum of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). 
      Therefore we investigated the cellular effects of PMC-II on human mesenchymal 
      progenitor cells (MPCs) as a model of cartilage and cartilage repair cells in the 
      inflamed and degenerating joint. DESIGN: MPCs were isolated from the trabecular 
      bone of patients undergoing reconstructive surgery and were differentiated into a 
      chondrogenic lineage. Cells were exposed to PMC-II and levels of the 
      proinflammatory mediators nitric oxide (*NO) and prostaglandin E(2) (PGE(2)) 
      measured. Levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 
      (COX-2), phosphorylated mitogen activated protein kinases (MAPKs) and nuclear 
      factor kappa B (NF-kappaB) activation were measured by enzyme linked 
      immunosorbent assay (ELISA) together with specific MAPK and NF-kappaB inhibitors. 
      RESULTS: PMC-II induced ()NO and PGE(2) synthesis through upregulation of iNOS 
      and COX-2 proteins. PMC-II also lead to the phosphorylation of MAPKs, 
      extracellularly regulated kinase 1/2 (ERK1/2) and p38 [but not c-Jun 
      NH(2)-terminal kinase (JNK1/2)] and the activation of proinflammatory 
      transcription factor NF-kappaB. Inhibitors of p38, ERK1/2 and NF-kappaB prevented 
      PMC-II induced ()NO and PGE(2) synthesis, iNOS and COX-2 protein expression and 
      NF-kappaB activation. CONCLUSION: iNOS, COX-2, NF-kappaB and MAPK are known to be 
      activated in the joints of patients with OA and RA. PMC-II induced iNOS and COX-2 
      synthesis through p38, ERK1/2 and NF-kappaB dependent pathways suggesting a 
      previously unidentified pathway for the synthesis of the proinflammatory 
      mediators, ()NO and PGE(2), further suggesting that inhibitors of these pathways 
      may be therapeutic in the inflamed and degenerating human joint.
FAU - Whiteman, M
AU  - Whiteman M
AD  - Department of Biochemistry, Yong Yoo Lin School of Medicine, National University 
      of Singapore, 8 Medical Drive, Republic of Singapore 117597. bchwml@nus.edu.sg
FAU - Spencer, J P E
AU  - Spencer JP
FAU - Zhu, Y Z
AU  - Zhu YZ
FAU - Armstrong, J S
AU  - Armstrong JS
FAU - Schantz, J-T
AU  - Schantz JT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060119
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Collagen Type II)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-kappa B)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Arthritis/physiopathology
MH  - Cell Differentiation/physiology
MH  - Cells, Cultured
MH  - Collagen Type II/*metabolism
MH  - Cyclooxygenase 2/metabolism
MH  - Dinoprostone/*biosynthesis
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Humans
MH  - Membrane Proteins/metabolism
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Peroxynitrous Acid/metabolism
MH  - Phosphorylation
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
EDAT- 2006/01/24 09:00
MHDA- 2006/10/18 09:00
CRDT- 2006/01/24 09:00
PHST- 2005/07/29 00:00 [received]
PHST- 2005/11/07 00:00 [accepted]
PHST- 2006/01/24 09:00 [pubmed]
PHST- 2006/10/18 09:00 [medline]
PHST- 2006/01/24 09:00 [entrez]
AID - S1063-4584(05)00314-6 [pii]
AID - 10.1016/j.joca.2005.11.002 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2006 May;14(5):460-70. doi: 10.1016/j.joca.2005.11.002. 
      Epub 2006 Jan 19.