Modulatory effects of inflammation and therapy on GDF-5 expression in rheumatoid arthritis synovium

被引：18

作者：

Bramlage, C. P. ^{[1
]}

Kaps, C. ^{[2
]}

Ungethuem, U. ^{[3
]}

Bramlage, P. ^{[4
]}

Koziolek, M. ^{[1
]}

Wessels, J. ^{[1
]}

Krenn, V. ^{[5
]}

Pruss, A. ^{[6
]}

Mueller, G. A. ^{[1
]}

Strutz, F. ^{[1
]}

Burmester, G-R. ^{[2
]}

Haeupl, T. ^{[2
]}

机构：

[1] Univ Gottingen, Dept Med Nephrol & Rheumatol, D-37075 Gottingen, Germany

[2] Charite Univ Med Berlin, Dept Rheumatol & Clin Immunol, Berlin, Germany

[3] Charite Univ Med Berlin, Lab Funct Genome Res, Berlin, Germany

[4] Med Fac Carl Gustav Carus, Inst Clin Pharmacol, Dresden, Germany

[5] Inst Pathol, Trier, Germany

[6] Charite Univ Med Berlin, Inst Transfus Med, Berlin, Germany

来源：

SCANDINAVIAN JOURNAL OF RHEUMATOLOGY | 2008年 / 37卷 / 06期

关键词：

D O I：

10.1080/03009740802120010

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: Growth differentiation factor-5 (GDF-5), a member of the transforming growth factor (TGF)-beta family, is involved in joint development during embryogenesis and has the potential to regenerate cartilage in adult animals. As progression of chronic joint diseases is influenced by cytokines of the synovial tissue, we examined the expression and effects of GDF-5 in this tissue. Methods: Microarray experiments were investigated for differential expression of GDF-5 in synovial tissues, synovial fibroblasts, and peripheral blood cells. GDF-5 expression was validated by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), immunohistochemistry, double immunofluorescence, and in situ hybridization in synovial tissue of normal donors (ND) and patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Effects of inflammation and therapy were investigated in RA and OA fibroblasts after stimulation with interleukin (IL)-1 beta, tumour necrosis factor (TNF)-alpha, methotrexate (MTX), and prednisolone. The influence of GDF-5 on macophages was studied by chemotaxis assay. Results: Microarray analysis and immunostaining revealed expression predominantly in synovial fibroblasts. Compared to patients without immunomodulating drugs, expression of GDF-5 was decreased significantly in patients receiving glucocorticoids and/or disease-modifying antirheumatic drugs (DMARDs) (p=0.007), but did not differ between the total group of ND, OA, and RA. Stimulation with prednisolone and TNF alpha reduced GDF-5 expression in OA and RA fibroblasts, whereas MTX and IL-1 beta revealed minor or no relevant change. GDF-5 also reduced cell migration of macrophages (p<0.001). Conclusion: GDF-5 is expressed in synovial fibroblasts and may counteract macrophage infiltration. Its modulation by inflammation and therapy suggests that glucocorticoids play a conflicting role by suppressing not only inflammation but also putative mechanisms of repair.

引用

页码：401 / 409

页数：9

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