5.9
CiteScore
5.9
Impact Factor
Volume 34 Issue 8
Aug.  2007
Turn off MathJax
Article Contents

Altered Gene Expression in Articular Chondrocytes of Smad3ex8/ex8 Mice, Revealed by Gene Profiling Using Microarrays

doi: 10.1016/S1673-8527(07)60079-4
More Information
  • Corresponding author: E-mail address: yangx@nic.bmi.ac.cn (Xiao Yang)
  • Received Date: 2007-03-19
  • Accepted Date: 2007-03-30
  • Available Online: 2007-08-21
  • Publish Date: 2007-08-20
  • It has been previously reported that small mother against decapentaplegic 3 (Smad3) gene knockout (Smad3ex8/ex8) mice displays phenotypes similar to human osteoarthritis, as characterized by abnormal hypertrophic differentiation of articular chondrocytes. To further clarify the crucial target genes that mediate transformation growth factor-β (TGF-β)/Smad3 signals on articular chondrocytes differentiation and investigate the underlying molecular mechanism of osteoarthritis, microarrays were used to perform comparative transcriptional profiling in the articular cartilage between Smad3ex8/ex8 and wild-type mice on day five after birth. The gene profiling results showed that the activity of bone morphogenetic protein (BMP) and TGF-β/cell division cycle 42 (Cdc42) signaling pathways were enhanced in Smad3ex8/ex8 chondrocytes. Moreover, there was altered gene expression in growth hormone/insulin-like growth factor 1 (Igf1) axis and fibroblast growth factor (Fgf) signaling pathway. Notably, protein synthesis related genes and electron transport chain related genes were upregulated in Smad3ex8/ex8 chondrocytes, implying that accelerated protein synthesis and enhanced cellular respiration might contribute to hypertrophic differentiation of articular chondrocytes and the pathogenesis of osteoarthritis.
  • loading
  • [1]
    Hicham, D, Michael, et al. Transcriptional regulation of chondrocyte maturation: Potential involvement of transcription factors in OA pathogenesis Mol Aspects Med, 26 (2005),pp. 169-179
    [2]
    Henry, MK Developmental regulation of the growth plate Nature, 423 (2003),pp. 332-336
    [3]
    Gerard, K, Erwin, et al. Reaching a genetic and molecular understanding of skeletal development Dev Cell, 2 (2002),pp. 389-406
    [4]
    Lefebvre, V, Smits, et al. Transcriptional control of chondrocyte fate and differentiation Birth Defects Res C Embryo Today, 75 (2005),pp. 200-212
    [5]
    Ballock, RT TGF-β1 prevents hypertrophy of epiphyseal chondrocytes: regulation of gene expression for cartilage matrix proteins and metalloproteases Dev Biol, 158 (1993),pp. 414-429
    [6]
    Tschan, T Autocrine or paracrine transforming growth factor-beta modulates the phenotype of chick embryo sternal chondrocytes in serumfree agarose culture J Biol Chem, 268 (1993),pp. 5156-5161
    [7]
    Dieudonne, SC Opposite effects of osteogenic protein and transforming growth factor beta on chondrogenesis in cultured long bone rudiments J Bone Miner Res, 9 (1994),pp. 771-780
    [8]
    Bohme, K Terminal differentiation of chondrocytes in culture is a spontaneous process and is arrested by transforming growth factor-beta 2 and basic fibroblast growth factor in synergy Exp Cell Res, 216 (1995),pp. 191-198
    [9]
    Serra, R Expression of a truncated, kinase-defective TGF-β type II receptor in mouse skeletal tissue promotes terminal chondrocyte differentiation and osteoarthritis J Cell Biol, 139 (1997),pp. 541-552
    [10]
    Dabovic, B Bone abnormalities in latent TGF-β binding protein (Ltbp)-3-null mice indicate a role for Ltbp-3 in modulating TGF-β bioavailability J Cell Biol, 156 (2002),pp. 227-232
    [11]
    Kizawa, H An aspartic acid repreat polymorphism in asporin inhibits chondrogenesis and increases susceptibility to ostesarthtitis Nature Genet, 37 (2005),pp. 138-144
    [12]
    Yang, X, Letterio, et al. Targeted disruption of SMAD3 results in impaired mucosal immunity and diminished T cell responsiveness to TGF-β EMBO J, 18 (1999),pp. 1280-1291
    [13]
    Yang, X, Chen, et al. TGF-β/Smad3 signals repress chondrocyte hypertrophic differentiation and are required for maintaining articular cartilage J Cell Biol, 153 (2001),pp. 35-46
    [14]
    Yao, JY Eur J Hum Genet, 11 (2003),pp. 714-717
    [15]
    [16]
    [17]
    [18]
    Li, X, Schwarz, et al. Retinoic acid stimulates chondrocyte differentiation and enhances bone morphogenetic protein effects through induction of Smad1 and Smad5 Endocrinology, 144 (2003),pp. 2514-2523
    [19]
    Lin, X, Duan, et al. PPM1A functions as a Smad phosphatase to terminate TGF-β signaling Cell, 125 (2006),pp. 915-928
    [20]
    Cristin, MF, Edward, et al. Smad2 and 3 mediate transforming growth factor-β1-induced inhibition of chondrocyte maturation Endocrinology, 141 (2000),pp. 4728-4735
    [21]
    Li, TF, Darowish, et al. Deficient chondrocytes have enhanced BMP signaling and accelerated differentiation J Bone Miner Res, 21 (2006),pp. 4-16
    [22]
    Southam, L, Chapman, et al. Genetic association analysis of BMP5 as a potential osteoarthritis susceptibility gene Rheumatology (Oxford), 42 (2003),pp. 911-912
    [23]
    Southam, L, Dowling, et al. Microsatellite association mapping of a primary osteoarthritis susceptibility locus on chromosome 6p12.3-q13 Arthritis Rheum, 50 (2004),pp. 3910-3914
    [24]
    Edlund, S, Landstrom, et al. Transforming growth factor-beta-induced mobilization of actin cytoskeleton requires signaling by small GTPases Cdc42 and RhoA Mol Biol Cell, 13 (2002),pp. 902-914
    [25]
    Bakin, AV, Rinehart, et al. p38 mitogen-activated protein kinase is required for TGF-β-mediated fibroblastic transdifferentiation and cell migration J Cell Sci, 115 (2002),pp. 3193-3206
    [26]
    Bhowmick, NA Transforming growth factor-b1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism Mol Biol Cell, 12 (2001),pp. 27-36
    [27]
    Derynck, R, Zhang, et al. Smad-dependent and Smad-indepen dent pathways in TGF-β family signaling Nature, 425 (2003),pp. 577-584
    [28]
    Wang, G, Beier, et al. Rac1/Cdc42 and RhoA GTPases antagonistically regulate chondrocyte proliferation, hypertrophy, and apoptosis J Bone Miner Res, 20 (2005),pp. 1022-1031
    [29]
    Tsukiyama-Kohara, K, Vidal, et al. Tissue distribution, genomic structure, and chromosome mapping of mouse and human eukaryotic initiation factor 4E-binding proteins 1 and 2 Genomics, 38 (1996),pp. 353-363
    [30]
    Pause, A, Belsham, et al. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5′-cap function Nature, 371 (1994),pp. 762-767
    [31]
    Lin, TA, Kong, et al. PHAS-I as a link between mitogen-activated protein kinase and translation initiation Science, 266 (1994),pp. 653-656
    [32]
    Clemens, MJ Translational regulation in cell stress and apoptosis. Roles of the eIF4E binding proteins J Cell Mol Med, 5 (2001),pp. 221-239
    [33]
    Stockwell, RA Chondrocytes J Clin Path, 12 (1978),pp. 7-13
    [34]
    Henrotin, YE, Bruckner, et al. The role of reactive oxygen species in homeostasis and degradation of cartilage Osteoarthritis Cartilage, 11 (2003),pp. 747-755
    [35]
    Hitchon, CA, El-Gabalawy, et al. Oxidation in rheumatoid arthritis Arthritis Res Ther, 6 (2004),pp. 265-278
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Article Metrics

    Article views (72) PDF downloads (0) Cited by ()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return