CTGF promotes articular damage by increased proliferation of fibroblast-like synoviocytes in rheumatoid arthritis
CTGF promotes articular damage by increased proliferation of fibroblast-like synoviocytes in rheumatoid arthritis
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DOI：
10.3109/03009742.2015.1092581
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发表时间：
2016-01-01
影响因子：
2.1
通讯作者：
Xiao, W.
中科院分区：
文献类型：
--
作者：
Ding, S.;Duan, H.;Xiao, W.
目的：成纤维细胞样滑膜细胞（FLS）是增生性滑膜血管翳的主要成分，在类风湿性关节炎（RA）病程中会侵袭软骨和骨。结缔组织生长因子（CTGF 或 CCN2）是生长因子诱导的立即早期基因的产物，参与细胞粘附、增殖和分化。然而，CTGF 在 FLS 增殖中所起的作用仍不清楚。本研究的目的是确定CTGF在调节RA患者FLS增殖中的作用。方法：通过酶联免疫吸附测定（ELISA）测定血清和滑液（SF）中的CTGF水平。使用逆转录聚合酶链反应（RT-PCR）测定FLS中CTGF的表达。通过胸苷掺入测量 CTGF 刺激的 FLS 增殖。采用流式细胞仪检测CTGF小干扰RNA（siRNA）对FLS凋亡的影响。结果：与正常对照样本相比，RA患者血清和SF样本中CTGF过表达。 RA SF 中 CTGF 水平升高促进了 FLS 的增殖。此外，在 RA 患者的样本中，发现 CTGF 可以保护 FLS 免于凋亡并维持 FLS 中生存素的表达。 FLS 中 CTGF 的表达可被肿瘤坏死因子 (TNF)-α 上调。结论：我们的研究结果表明，CTGF 在 RA 中 FLS 的增殖中起着至关重要的作用，并可能导致 RA 患者滑膜衬里细胞增生，并最终导致关节破坏。
Objectives: Fibroblast-like synoviocytes (FLS) are a major component of the hyperplastic synovial pannus, which aggressively invades cartilage and bone during the course of rheumatoid arthritis (RA). Connective tissue growth factor (CTGF or CCN2) is a product of a growth factor-inducible immediate early gene and is involved in cell adhesion, proliferation, and differentiation. However, the role that CTGF plays in FLS proliferation has remained undetermined. The aim of this study was to identify the role of CTGF in regulating the proliferation of FLS derived from patients with RA.Method: CTGF levels in serum and synovial fluid (SF) were determined by enzyme-linked immunosorbent assay (ELISA). Expression of CTGF in FLS was determined using reverse transcription polymerase chain reaction (RT-PCR). FLS proliferation stimulated by CTGF was measured by thymidine incorporation. The influence of CTGF small interfering RNA (siRNA) on FLS apoptosis was detected by flow cytometry.Results: CTGF was overexpressed in serum and SF samples from RA patients compared with samples from normal controls. Elevated levels of CTGF in RA SF promoted the proliferation of FLS. Furthermore, in samples from RA patients, CTGF was found to protect FLS from apoptosis and to sustain the expression of survivin in FLS. The expression of CTGF in FLS can be up-regulated by tumour necrosis factor (TNF)-alpha.Conclusions: Our findings indicate that CTGF plays a crucial role in the proliferation of FLS in RA and probably contributes to synovial lining cell hyperplasia and eventually to joint destruction in patients with RA.