Nicotinamide Phosphoribosyltransferase Is Essential for Interleukin-1 beta-mediated Dedifferentiation of Articular Chondrocytes via SIRT1 and Extracellular Signal-regulated Kinase (ERK) Complex Signaling
- Title
- Nicotinamide Phosphoribosyltransferase Is Essential for Interleukin-1 beta-mediated Dedifferentiation of Articular Chondrocytes via SIRT1 and Extracellular Signal-regulated Kinase (ERK) Complex Signaling
- Author
- 이수재
- Keywords
- GENE-EXPRESSION; DIFFERENTIATED PHENOTYPE; LIFE-SPAN; CARTILAGE; APOPTOSIS; OSTEOARTHRITIS; BIOSYNTHESIS; INFLAMMATION; RESTRICTION; EXTENSION
- Issue Date
- 2011-08
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY; AUG 12 2011, 286, 32, p28619-p28631
- Abstract
- Although much is known about interleukin (IL)-1 beta and its role as a key mediator of cartilage destruction in osteoarthritis, only limited information is available on IL-1 beta signaling in chondrocyte dedifferentiation. Here, we have characterized the molecular mechanisms leading to the dedifferentiation of primary cultured articular chondrocytes by IL-1 beta treatment. IL-1 beta or lipopolysaccharide, but not phorbol 12-myristate 13-acetate, retinoic acid, or epidermal growth factor, induced nicotinamide phosphoribosyltransferase (NAMPT) expression, showing the association of inflammatory cytokines with NAMPT regulation. SIRT1, in turn, was activated NAMPT-dependently, without any alteration in the expression level. Activation or inhibition of SIRT1 oppositevely regulates IL-1 beta-mediated chondrocyte dedifferentiation, suggesting this protein as a key regulator of chondrocytes phenotype. SIRT1 activation promotes induction of ERK and p38 kinase activities, but not JNK, in response to IL-1 beta. Subsequently, ERK and p38 kinase activated by SIRT1 also induce SIRT1 activation, forming a positive feedback loop to sustain downstream signaling of these kinases. Moreover, we found that the SIRT1-ERK complex, but not SIRT1-p38, is engaged in IL-1 beta-induced chondrocyte dedifferentiation via a Sox-9-mediated mechanism. JNK is activated by IL-1 beta and modulates dedifferentiation of chondrocytes, but this pathway is independent on NAMPT-SIRT1 signaling. Based on these findings, we propose that IL-1 beta induces dedifferentiation of articular chondrocytes by up-regulation of SIRT1 activity enhanced by both NAMPT and ERK signaling.
- URI
- http://www.jbc.org/content/286/32/28619http://eds.a.ebscohost.com.access.hanyang.ac.kr/eds/detail/detail?vid=0&sid=dc3fa0ac-92ec-47d5-b247-91ad83fd08ff%40sessionmgr4008&bdata=Jmxhbmc9a28mc2l0ZT1lZHMtbGl2ZQ%3d%3d#AN=edselc.2-52.0-80051536994&db=edselc
- ISSN
- 0021-9258
- DOI
- 10.1074/jbc.M111.219832
- Appears in Collections:
- COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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