Nicotinamide Phosphoribosyltransferase Is Essential for Interleukin-1 beta-mediated Dedifferentiation of Articular Chondrocytes via SIRT1 and Extracellular Signal-regulated Kinase (ERK) Complex Signalingopen access
- Authors
- Hong, Eun-Hee; Yun, Hong Shik; Kim, Jongdoo; Um, Hong-Duck; Lee, Kee-Ho; Kang, Chang-Mo; Lee, Su-Jae; Chun, Jang-Soo; Hwang, Sang-Gu
- Issue Date
- Aug-2011
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.286, no.32, pp.28619 - 28631
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 286
- Number
- 32
- Start Page
- 28619
- End Page
- 28631
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/28094
- DOI
- 10.1074/jbc.M111.219832
- ISSN
- 0021-9258
- 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.
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