Caveolin-p38MAPK Signal PathwaysThe Potential Molecu_x005flar Targets for Osteoarthritis
Abstract
pathways affect a variety of intracellular responses, with well-recognized roles in osteoarthritis, due to in vitro and in vivo evidence that this
pathway is significantly involved in the pathogenesis of arthritis, it has been the focus of much attention in drug development in recent years,
but inhibitors of p38 kinase have largely failed in clinical trials, due to both lack of efficacy and adverse events. In recent research, Caveolin-1 down-expression suppressed excessive inflammation-stimulated phosphorylation of p38 to inhibit the activity of p38MAPK signal pathways, In this review, we focus on the potential molecular targets of cavoelin-p38MAPK signal pathways for osteoarthritis, We summarize
how this pathway has been exploited for the development of therapeutics and discuss the potential obstacles of targeting this pathway for the
treatment of osteoarthritis.
Keywords
Full Text:
PDFReferences
[1] Lawrence RC, Felson DT, Helmick CG, Arnold LM, Choi H, et al. (2008)Estimates of the prevalence of arthritis and other rheu_x005fmatic conditions in the United States. Part II. Arthritis Rheum 58: 26–35.
[2] Zhang W, Nuki G, Moskowitz RW, Abramson S, Altman RD, Arden NK, Bierma-Zeinstra S, Brandt KD, Croft P, Doherty M, Dougados M, Hochberg M, Hunter DJ, Kwoh K, Lohmander LS, Tugwell P: OARSI recommendations for the management of hip and knee os-
teoarthritis. Part III: changes in evidence following systematic cumulative update of research published through January 2009. Osteoarthritis
Cartilage 2010, 18:476–499.
[3] Matchaba P, Gitton X, Krammer G, Ehrsam E, Sloan VS, et al. (2005) Cardiovascular safety of lumiracoxib: A meta-analysis of all
randomized controlled trials 1 week and up to 1 year in duration of patients with osteoarthritis and rheumatoid arthritis. Clin Ther 27: 1196–
1214.
[4] Hunziker, E.B. 2002. Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage. 10:432–463.
[5] Fryback DG, Dasbach EJ, Klein R, Klein BE, Dorn N, Peterson K, Martin PA: The Beaver Dam Health Outcomes Study: initial
catalog of health-state quality factors. Med Decis Making 1993, 13:89–102.
[6] Tetlow LC, Adlam DJ, Woolley DE: Matrix metalloproteinase and proinflammatory cytokine production by chondrocytes of human
osteoarthritic cartilage: associations with degenerative changes. Ar thritis Rheum 2001,44(3):585 – 594.
[7] Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H: Role ofproinflammatory cytokines in the pathophysiology of
osteoarthritis. Nat Rev Rheumatol 2011,7(1):33– 42.
[8] Loeser RF, Erickson EA, Long DL: Mitogen-activated protein kinases as therapeutic targets in o steoarthritis. Curr Opin Rheumatol
2008,20:581-586.
[9] Kumar S, Votta BJ, Rieman DJ, Badger AM, Gowen M, Lee JC: IL-1- and TNF-induced bone resorption is mediated by p38 mitogen activated protein kinase.J C ell Physiol 2001,187 :294-303
[10] Liacini A, Sylvester J, Li WQ, Huang W, Dehnade F, Ahmad M, Zafarullah M:Induction of matrix metalloproteinase-13 gene
expression by TNF-alpha is mediated by MAP kinases, AP-1, and NF-kappaB transcription factors in articular chondrocytes. Exp Cell Res
2003,288 (1):208 – 217.
[11] G Schett, J Zwerina, and G Firestein. The p38 mitogen-activated protein kinase (MAPK) pathway in rheumatoid arthritis Ann
Rheum Dis. 2008 ,7 ; 67(7): 909–916.
[12] Han J, et al. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells.
Science. 1994; 265:808–811.
[13] Marinissen MJ, Chiariello M, Gutkind JS. Regulation of gene expression by the small GTPase Rho through the ERK6 (p38 gamma) MAP kinase pathway. Genes Dev 2001;15:535–553.
[14] Juo P, Kuo CJ, Reynolds SE, Konz RF, Raingeaud J, Davis RJ, et al. Fas activation of the p38 mitogen-activated protein kinase
signalling pathway requires ICE/CED-3 family proteases. Mol Cell Biol1997;17:24–35.
[15] Badger AM, Griswold DE, Kapadia R, Blake S, Swift BA, Hoffmann SJ, et al. a selective inhibitor of mitogen-activated protein
kinase, in rat adjuvant arthritis. Arthritis Rheum 2000;43:75–83.
[16] Chan ED, Winston BW, Uh ST, Wynes MW, Rose DM, Riches DW. Evaluation of the role of mitogen-activated protein kinases in
the expression of inducible nitric oxide synthase by IFN-gamma and TNF-alpha in mouse macrophages. J Immunol 1999;162:415–422.
[17] Peifer, C.; Wagner, G.; Laufer, S. New approaches to the treatment of inflammatory disorders small molecule inhibitors of p38
MAP kinase. Curr. Top. Med. Chem,2006, 6 (2), 113-149.
[18] Foltz IN, Lee JC, Young PR, Schrader JW. Hemopoietic growth factors with the exception of interleukin-4 activate the p38 mito-gen-activated protein kinase pathway. J Biol Chem,1997; 272:3296-3301.
[19] Tyler ZARUBIN, Jia-huai HAN. Activation and signaling of the p38 MAP kinase pathway. Cell Research, 2005,15(1):11-18.
[20] Cuenda A, Cohen P, Buee-Scherrer V, Goedert M. Activation of stress-activated protein kinase-3 (SAPK3) by cytokines and cellular stresses is mediated via SAPKK3 (MKK6); comparison of the specificities of SAPK3 and SAPK2 (RK/p38). EMBO J 1997; 16:295-305.
[21] Schindler JF, et al. p38 pathway kinases as anti-inflammatory drug targets. J. Dent. Res. 2007;86:800–811.
[22] Cohen P. Targeting protein kinases for the development of anti-inflammatory drugs. Curr. Opin.Cell Biol. 2009; 21:317–324.
[23] Martin JA, Buckwalter JA. Telomere erosion and senescence in human articular cartilage
chondrocytes. J Gerontol A Biol Sci Med Sci. 2001; 56:B172–9.
[24] Dai SM, Shan ZZ, Nakamura H, Masuko-Hongo K, Kato T, Nishioka K, Yudoh K. Catabolic stress induces features of chondrocyte senescence through overexpression of caveolin 1: possible involvement of caveolin 1-induced down-regulation of articular chondrocytes
in the pathogenesis of osteoarthritis. Arthritis Rheum. 2006; 54:818–31.
[25] Yudoh K, Shi Y, Karasawa R. Angiogenic growth factors inhibit chondrocyte ageing in osteoarthritis:potential involvement of catabolic stress-induced overexpression of caveolin-1 in cellular ageing.Int J Rheum Dis. 2009; 12:90–9.
[26] Dasari A, Bartholomew JN, Volonte D, Galbiati F. Oxidative stress induces premature senescence by stimulating caveolin-1 gene
transcription through p38 mitogen-activated protein kinase/Sp1-mediated activation of two GC-rich promoter elements. Cancer Res. 2006;
66:10805–14.
DOI: http://dx.doi.org/10.18686/nursing.v12i4.320
Refbacks
- There are currently no refbacks.
Copyright (c) 2023 Hu Yan,Limeng Sun