Expression profiles and functional analyses of Wnt-related genes in human joint disorders

被引:125
作者
Nakamura, Y
Nawata, M
Wakitani, S
机构
[1] Shinshu Univ, Sch Med, Dept Orthopaed Surg, Matsumoto, Nagano 3908621, Japan
[2] Case Western Reserve Univ, Howard Hughes Med Inst, Dept Genet, Cleveland, OH 44106 USA
关键词
D O I
10.1016/S0002-9440(10)62957-4
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Rheumatoid arthritis (RA) and osteoarthritis (OA) are joint disorders that cause major public health problems. Previous studies of the etiology of RA and OA have implicated Wnt genes, although the exact nature of their involvement remains unclear. To further clarify the relationship between RA, OA, and the Wnt gene family, gene expression analyses were performed on articular cartilage, bone, and synovial tissues in knee joints taken from RA, OA, and normal/control patients. Cytokine assays were also performed in cells transfected with Wnt-7b, a member of the gene family most closely linked to RA and OA. Of the human Wnt genes, real-time PCR analysis revealed significant up-regulation of Wnt-7b in OA cartilage and RA synovium. In situ hybridization and immunohistochemistry also revealed that Wnt-7b was present in articular cartilage, bone, and synovium. of RA samples and in osteophytes, articular cartilage, bone marrow, and synovium of OA samples. The levels of the cytokines tumor necrosis factor-alpha, interleukin-1 beta, and interieukin-6 were significantly increased in RA synovium and Wnt-7b-transfected normal synovial cells when compared with normal samples. These results point to the potential involvement of Wnt signaling in the pathobiology of both RA and OA.
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页码:97 / 105
页数:9
相关论文
共 34 条
[11]   Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal morphogenesis [J].
Hoang, B ;
Moos, M ;
Vukicevic, S ;
Luyten, FP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (42) :26131-26137
[12]   Biochemical characterization of Wnt-Frizzled interactions using a soluble, biologically active vertebrate Wnt protein [J].
Hsieh, JC ;
Rattner, A ;
Smallwood, PM ;
Nathans, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (07) :3546-3551
[13]   Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with β-catenin [J].
Hsu, SC ;
Galceran, J ;
Grosschedl, R .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (08) :4807-4818
[14]  
Ijiri K, 2002, J RHEUMATOL, V29, P2266
[15]  
IWAMOTO M, 2001, JIKKEN IGAKU, V19, P1210
[16]  
Kühl M, 2000, TRENDS GENET, V16, P279, DOI 10.1016/s0168-9525(00)02028-x
[17]  
Letamendia A, 2001, J BONE JOINT SURG AM, V83A, pS31
[18]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408
[19]   Mechanism and function of signal transduction by the Wnt/β-catenin and Wnt/Ca2+ pathways [J].
Miller, JR ;
Hocking, AM ;
Brown, JD ;
Moon, RT .
ONCOGENE, 1999, 18 (55) :7860-7872
[20]   XTcf-3 transcription factor mediates beta-catenin-induced axis formation in Xenopus embryos [J].
Molenaar, M ;
vandeWetering, M ;
Oosterwegel, M ;
PetersonMaduro, J ;
Godsave, S ;
Korinek, V ;
Roose, J ;
Destree, O ;
Clevers, H .
CELL, 1996, 86 (03) :391-399