Limited efficacy of COX-2 inhibitors on nerve growth factor and metalloproteinases expressions in human synovial fibroblasts

Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association
Makiko YorifujiKengo Yamamoto

Abstract

Nerve growth factor (NGF) is associated with arthritic pain and metalloproteinases are implicated in collagen and aggrecan degradation. Although selective COX-2 inhibitors are recommended for the treatment of arthritic diseases, their effects on NGF and metalloproteinases remain unclear. This study investigated the regulations of NGF and metalloproteinases by selective COX-2 inhibitors in isolated human synovial cells. The isolated human synovial cells were stimulated with IL-1β in the presence of selective COX-2 inhibitors (NS-398 or celecoxib) with or without exogenous PGE2 or its receptor (EP1-4) agonists. The expressions of NGF, MMP-1, -3, -13, ADAMTS-4, and -5 were quantified by real-time PCR and their proteins were determined by Western blotting. The amount of PGE2 released was measured by enzyme-linked immunosorbent assay (ELISA). The IL-1β inductions of NGF and MMP-1 and MMP-13 were augmented by the COX-2 inhibitors, whereas the inductions of ADAMTS-4 and ADAMTS-5 were inhibited. These actions were reversed by supplementing PGE2 or the EP4 agonist exogenously. Our comprehensive analysis revealed that COX-2 inhibitors may be beneficial for suppressing aggrecan degradation and for reducing inflammatory pain by inhibiting ...Continue Reading

References

Aug 1, 1990·Annals of the Rheumatic Diseases·B L KiddJ M Polak
Mar 29, 2002·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·C William WuA Robin Poole
Aug 2, 2003·The Journal of Biological Chemistry·Michael A PrattaElizabeth C Arner
Aug 31, 2004·Arthritis and Rheumatism·Sonya S GlassonElisabeth A Morris
Sep 10, 2005·Endocrinology·Ikuko TakeNaoyuki Takahashi
Nov 1, 2008·Arthritis and Rheumatism·Yasunobu SawajiJeremy Saklatvala
Sep 18, 2010·Arthritis and Rheumatism·Manuel J Del ReyJosé L Pablos
Oct 15, 2010·The New England Journal of Medicine·Nancy E LaneMark T Brown
Sep 15, 2011·Biochimica Et Biophysica Acta·Heather StantonAmanda J Fosang
Jan 17, 2012·Arthritis and Rheumatism·Joseph R GhilardiPatrick W Mantyh
Dec 1, 2010·Therapeutic Advances in Musculoskeletal Disease·Claire Y J Wenham, Philip G Conaghan
Feb 2, 2013·HSS Journal : the Musculoskeletal Journal of Hospital for Special Surgery·Bruce Kidd

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