GDF-5 is suppressed by IL-1β and enhances TGF-β3-mediated chondrogenic differentiation in human rheumatoid fibroblast-like synoviocytes

被引：15

作者：

Liu, Fei-Lan ^{[2
]}

Lin, Li-Hsiang ^{[1
]}

Sytwu, Huey-Kang ^{[3
]}

Chang, Deh-Ming ^{[1
]}

机构：

[1] Natl Def Med Ctr, Triserv Gen Hosp, Taipei, Taiwan

[2] Natl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan

[3] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan

来源：

EXPERIMENTAL AND MOLECULAR PATHOLOGY | 2010年 / 88卷 / 01期

关键词：

Growth differentiation factor-5; Chondrocyte; Interleukin-1; Transforming growth factor-b; MESENCHYMAL STEM-CELLS; ACTIVATED PROTEIN-KINASE; SYNOVIAL FIBROBLASTS; MORPHOGENETIC PROTEIN-1; BONE-MARROW; IN-VITRO; GROWTH/DIFFERENTIATION FACTOR-5; OSTEOGENIC PROTEIN-1; SKELETAL DEVELOPMENT; ARTICULAR-CARTILAGE;

D O I：

10.1016/j.yexmp.2009.09.019

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Objective: To investigate the expression of growth differentiation factor-5 (GDF-5) in chondrocytes (HC) and fibroblast-like synoviocytes (FLS) from humans with rheumatoid arthritis (RA) when stimulated with proinflammatory cytokines and to explore whether GDF-5 plays a role in regulating the differentiation of FLS-RA into chondrocytes. Methods: Expression of GDF-5 in synovium and cartilage in RA and osteoarthritis (OA) was assessed by immunohistochemistry. GDF-5 production in FLS-RA and HC-RA was examined through real-time quantitative RT-PCR (Q-PCR) and western blotting. Expressions of GDF-associated receptors on FLS-RA were determined by semiquantitative-PCR, and MTT assay was used to study the effects on FLS-RA proliferation. Effect of GDF-5 and TGF-beta 3 on in vitro chondrogenic ability of FLS-RA was investigated using pellet-culture system, Q-PCR and histological analysis. Results: Immunohistochemical analysis demonstrated that GDF-5 expression in the synovium and cartilage from joints of RA patients was much lower than that of OA patients. Addition of IL-1 beta or TNF-alpha appeared to downregulate the expression of GDF-5 in HC-RA and FLS-RA. Inhibition of GDF-5 expression by IL-1 beta in RA-FLS was attenuated by pretreatment with MEK1/2 inhibitor. GDF-5-associated receptors were expressed in FLS-RA, but GDF-5 had no effect on FLS-RA proliferation. GDF-5 had a strong chondrogenic-promoting effect on TGF-beta 3-induced chondrocyte differentiation in FLS-RA. Conclusions: GDF-5 is expressed in FLS-RA and HC-RA, and its expression is strongly downregulated by proinflammatory cytokines. MEK-ERK pathway is a negative regulator of GDF-5 expression in FLS-RA. In FLS-RA, synergy between GDF-5 and TGF-beta 3 enhances chondrogenesis. Anti-inflammatory drugs combined with GDF-5 might be a new therapeutic treatment for RA. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：163 / 170

页数：8

共 44 条

[1] THE AMERICAN-COLLEGE-OF-RHEUMATOLOGY CRITERIA FOR THE CLASSIFICATION AND REPORTING OF OSTEOARTHRITIS OF THE HIP [J].

ALTMAN, R ;

ALARCON, G ;

APPELROUTH, D ;

BLOCH, D ;

BORENSTEIN, D ;

BRANDT, K ;

BROWN, C ;

COOKE, TD ;

DANIEL, W ;

FELDMAN, D ;

GREENWALD, R ;

HOCHBERG, M ;

HOWELL, D ;

IKE, R ;

KAPILA, P ;

KAPLAN, D ;

KOOPMAN, W ;

MARINO, C ;

MCDONALD, E ;

MCSHANE, DJ ;

MEDSGER, T ;

MICHEL, B ;

MURPHY, WA ;

OSIAL, T ;

RAMSEYGOLDMAN, R ;

ROTHSCHILD, B ;

WOLFE, F .

ARTHRITIS AND RHEUMATISM, 1991, 34 (05) :505-514

[2] THE AMERICAN-RHEUMATISM-ASSOCIATION 1987 REVISED CRITERIA FOR THE CLASSIFICATION OF RHEUMATOID-ARTHRITIS [J].

ARNETT, FC ;

EDWORTHY, SM ;

BLOCH, DA ;

MCSHANE, DJ ;

FRIES, JF ;

COOPER, NS ;

HEALEY, LA ;

KAPLAN, SR ;

LIANG, MH ;

LUTHRA, HS ;

MEDSGER, TA ;

MITCHELL, DM ;

NEUSTADT, DH ;

PINALS, RS ;

SCHALLER, JG ;

SHARP, JT ;

WILDER, RL ;

HUNDER, GG .

ARTHRITIS AND RHEUMATISM, 1988, 31 (03) :315-324

[3] Cartilage-derived morphogenetic protein-1 and-2 are endogenously expressed in healthy and osteoarthritic human articular chondrocytes and stimulate matrix synthesis [J].

Bobacz, K ;

Gruber, R ;

Soleiman, A ;

Graninger, WB ;

Luyten, FP ;

Erlacher, L .

OSTEOARTHRITIS AND CARTILAGE, 2002, 10 (05) :394-401

[4] Differentially regulated expression of growth differentiation factor 5 and bone morphogenetic protein 7 in articular cartilage and synovium in murine chronic arthritis [J].

Bobacz, Klaus ;

Sunk, Ilse-Gerlinde ;

Hayer, Silvia ;

Amoyo, Love ;

Tohidast-Akrad, Makiyeh ;

Kollias, George ;

Smolen, Josef S. ;

Schett, Georg .

ARTHRITIS AND RHEUMATISM, 2008, 58 (01) :109-118

[5] The MEK-ERK signaling pathway is a negative regulator of cartilage-specific gene expression in embryonic limb mesenchyme [J].

Bobick, BE ;

Kulyk, WM .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (06) :4588-4595

[6] Modulatory effects of inflammation and therapy on GDF-5 expression in rheumatoid arthritis synovium [J].

Bramlage, C. P. ;

Kaps, C. ;

Ungethuem, U. ;

Bramlage, P. ;

Koziolek, M. ;

Wessels, J. ;

Krenn, V. ;

Pruss, A. ;

Mueller, G. A. ;

Strutz, F. ;

Burmester, G-R. ;

Haeupl, T. .

SCANDINAVIAN JOURNAL OF RHEUMATOLOGY, 2008, 37 (06) :401-409

[7]

Buxton P, 2001, J BONE JOINT SURG AM, V83A, pS23

[8]

Catterall JB, 2001, ARTHRITIS RHEUM-US, V44, P2296, DOI 10.1002/1529-0131(200110)44:10<2296::AID-ART392>3.0.CO

[9]

2-9

[10] Activin A suppresses interleukin-1-induced matrix metalloproteinase 3 secretion in human chondrosarcoma cells [J].

Chang, Deh-Ming ;

Liu, Shao-Hsiang ;

Lee, Herng-Sheng ;

Lai, Jenn-Hung ;

Chen, Chen-Hung .

RHEUMATOLOGY INTERNATIONAL, 2007, 27 (11) :1049-1055

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