Arthritogenic action of gliostatin in rheumatoid arthritis and its molecular mechanism.

胶质抑素在类风湿性关节炎中的致关节炎作用及其分子机制。

• 批准号: 13671529
• 负责人: OTSUKA Takanobu
• 金额: $ 2.24万
• 依托单位: Nagoya City University, Graduate School of Medical Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671529/
• 关键词: gliostatin; platelet-derived endothelial cell growth factor; thymidine phosphorylase; rheumatoid arthritis; synoviocytes; rabbit; matrix metalloproteinases; arthroplasty; 関節内注射; 滑膜切除術; Matrix metallopoteinases

Neovascularization, proliferation of synovial cells, and mononuclear cell influx and activation are characteristic events observed in synovial joints in the pathohistology of rheumatoid arthritis (RA). The purposes of this study are to examine how gliostatin/platelet derived-endothelial cell growth factor (GLS/PD-ECGF) is involved in the molecular mechanism of cartilage degradation and whether measurement of serum GLS can be used to evaluate symptomatic improvements after surgery (arthroplasty or synovectomy) in RA.Intraarticular injection of rHuGLS in rabbit knee joints resulted in development of diffuse synovitis, chondrocytes destruction, and pannus formation resembling rheumatoid arthritis. A chondrosarcoma cell line (OUMS-27) was cultured and treated with interleukin-lβ (IL-1β). IL-1β induced the expression of matrix metalloproteinase (MMP)-1, MMP-13, and GLS. Patients with RA undergoing arthroplasty demonstrated a decrease in serum GLS levels after operations.These findings suggest that GLS is a plausible pathogenic factor causing the extensive joint destruction in RA mediated via MMPs and that human GLS can cause RA-like synovitis via a mechanism other than its thymidine phosphorylase activity and that the serum GLS level is a useful indicator for evaluation of synovitis and the systemic efficacy of surgical treatment.

新血管形成、滑膜细胞增殖以及单核细胞流入和激活是类风湿性关节炎（RA）病理组织学中滑膜关节中观察到的特征事件。本研究的目的是探讨胶质抑素/血小板衍生内皮细胞生长因子 (GLS/PD-ECGF) 如何参与软骨退化的分子机制，以及血清 GLS 的测量是否可用于评估 RA 手术（关节成形术或滑膜切除术）后症状的改善。在兔膝关节中关节内注射 rHuGLS 导致发育 弥漫性滑膜炎、软骨细胞破坏和类似于类风湿性关节炎的血管翳形成。培养软骨肉瘤细胞系（OUMS-27）并用白细胞介素-1β（IL-1β）处理。 IL-1β 诱导基质金属蛋白酶 (MMP)-1、MMP-13 和 GLS 的表达。接受关节置换术的 RA 患者术后血清 GLS 水平下降。这些研究结果表明，GLS 可能是通过 MMP 介导的 RA 广泛关节破坏的致病因素，人类 GLS 可以通过胸苷磷酸化酶活性以外的机制引起 RA 样滑膜炎，并且血清 GLS 水平是评估滑膜炎和全身疗效的有用指标。 手术治疗。

项目成果

松井宣夫, 永谷祐子: "慢性関節リウマチ-21世紀に向けての診断と治療-"中部リウマチ(J Chubu Rheum Assoc). 32. 10-16 (2001)

Nobuo Matsui，Yuko Nagatani：“慢性类风湿性关节炎 - 21 世纪的诊断和治疗” Chubu Rheum Assoc。 32. 10-16 (2001)

Ieda Y, Waguri-Nagaya Y, Otsuka T, et al.: "IL-1β induced expression of matrix metalloproteinases and gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) in a chondrosarcoma cell line (OUMS-27)"Rheumatol Int.. 21. 45-52 (2001)

Ieda Y、Waguri-Nagaya Y、Otsuka T 等人：“IL-1β 诱导软骨肉瘤细胞系 (OUMS-27) 中基质金属蛋白酶和胶质抑素/血小板衍生内皮细胞生长因子 (GLS/PD-ECGF) 的表达)“风湿病国际.. 21. 45-52 (2001)

Ieda Y, Waguri-Nagaya Y, Otsuka T, et al.: "IL-1B induced expression of MMP and gliostatin/PbECGF in chondrosareoua cell line (OUMS-27)"Rheumafology International. 21. 45-52 (2001)

Ieda Y、Waguri-Nagaya Y、Otsuka T 等人：“IL-1B 在软骨细胞系 (OUMS-27) 中诱导 MMP 和胶质抑素/PbECGF 的表达”Rheumafology International。

Matsui N, Waguri-Nagaya Y, Taneda Y: "Diagnosis and therapy of rheumatoid arthritis in the future"Mod Rheumatol. 11. 286-291 (2001)

Matsui N、Waguri-Nagaya Y、Taneda Y：“未来类风湿性关节炎的诊断和治疗”Mod Rheumatol。

Muro H, Waguri-Nagaya Y, Otsuka T, et al.: "Serum gliostatin levels in patients with rheumatoid factor-negative and -positive rheumatoid arthritis and changes of these levels after surgical treatment"Clin Rheumatol. 20. 331-336 (2001)

Muro H、Waguri-Nagaya Y、Otsuka T 等人：“类风湿因子阴性和阳性类风湿性关节炎患者的血清胶质抑素水平以及手术治疗后这些水平的变化”Clin Rheumatol。