Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.joca.2005.11.002
Title: Peroxynitrite-modified collagen-II induces p38/ERK and NF-κB-dependent synthesis of prostaglandin E2and nitric oxide in chondrogenically differentiated mesenchymal progenitor cells
Authors: Whiteman, M. 
Armstrong, J.S. 
Spencer, J.P.E.
Zhu, Y.Z. 
Schantz, J.-T. 
Keywords: Chondrocyte
Nitric oxide
Osteoarthritis
Peroxynitrite
Rheumatoid arthritis
Issue Date: 2006
Source: Whiteman, M., Armstrong, J.S., Spencer, J.P.E., Zhu, Y.Z., Schantz, J.-T. (2006). Peroxynitrite-modified collagen-II induces p38/ERK and NF-κB-dependent synthesis of prostaglandin E2and nitric oxide in chondrogenically differentiated mesenchymal progenitor cells. Osteoarthritis and Cartilage 14 (5) : 460-470. ScholarBank@NUS Repository. https://doi.org/10.1016/j.joca.2005.11.002
Abstract: 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 ({radical dot}NO) and prostaglandin E2 (PGE2) 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-κB) activation were measured by enzyme linked immunosorbent assay (ELISA) together with specific MAPK and NF-κB inhibitors. Results: PMC-II induced {radical dot}NO and PGE2 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 NH2-terminal kinase (JNK1/2)] and the activation of proinflammatory transcription factor NF-κB. Inhibitors of p38, ERK1/2 and NF-κB prevented PMC-II induced {radical dot}NO and PGE2 synthesis, iNOS and COX-2 protein expression and NF-κB activation. Conclusion: iNOS, COX-2, NF-κB 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-κB dependent pathways suggesting a previously unidentified pathway for the synthesis of the proinflammatory mediators, {radical dot}NO and PGE2, further suggesting that inhibitors of these pathways may be therapeutic in the inflamed and degenerating human joint. © 2005 OsteoArthritis Research Society International.
Source Title: Osteoarthritis and Cartilage
URI: http://scholarbank.nus.edu.sg/handle/10635/27410
ISSN: 10634584
DOI: 10.1016/j.joca.2005.11.002
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