Regulation mechanism of nsulin-like growth factor-binding proteins producion in osteoarthritis.

骨关节炎中胰岛素样生长因子结合蛋白产生的调节机制。

• 批准号: 09671503
• 负责人: MATSUMOTO Tomoko
• 金额: $ 1.86万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671503/
• 关键词: Osteoarthritis; IGF-bimding protein; Isulin-like growth factor-1

Thc destruction of cartilage tissue causes functional disability in osteoarthritis. The repair of cartilage tissue are supposed to be disturbed in this disease. Insulin-like growth factor (IGF) is an anabolic factor for chondrocytes and is regulated by binding proteins (IGPBPs). We assumed that the effect of IGF-I on chondrocytes are disturbed in osteoarthritis. So we tried to study the IGFBPs produced by human chondrocytes, which may regulate IGE action. Employing Western-ligand blotting (WLB) and immunoprecipitation, immortalized humah chondrocytes were found to secrete IGFBP-2, -3, -4 and -5. Treatment of cells with IGF-I resulted in a dose-dependent increase of IGFBP-5. The IGFBPs associated with cell membrane were examined by affinity cross-linking method, showing the IGFBP-3 and -5 as well as type 1 LGF and type 2 [GE receptor. To clarify the changes of IGFBPs in osteoarthritis, interleukin-1b is added to the culture medium. Unfortunately, there was no difference between them, with /without interleukin-1. We should further study the regulation mechanism of IGEBP production in osteoarthritis by using human cartilage tissue obtained by operated sample.

软骨组织的破坏导致骨关节炎的功能障碍。软骨组织的修复在这种疾病中被认为是受到干扰的。胰岛素样生长因子（IGF）是软骨细胞的合成代谢因子，受结合蛋白（IGPBPs）调节。我们假设在骨关节炎中IGF-I对软骨细胞的作用受到干扰。因此，我们试图研究人软骨细胞产生的IGFBPs，它可能调节IGE的作用。采用免疫印迹和免疫沉淀法，发现永生化人软骨细胞分泌IGFBP-2、-3、-4和-5。用IGF-I处理细胞导致IGFBP-5的剂量依赖性增加。通过亲和交联法检测与细胞膜结合的IGFBP，显示IGFBP-3和IGFBP-5以及1型LGF和2型[GE]受体。为了阐明IGFBPs在骨关节炎中的变化，将白细胞介素-1b添加到培养基中。不幸的是，在有/没有白细胞介素-1的情况下，它们之间没有差异。骨关节炎时IGEBP产生的调控机制有待于进一步研究。

项目成果

Adashi EY: "The mouse intraovarian insulin-like growth factor 1 system:departure from the rat paradigm." Endocrinology. 138. 3881-3890 (1997)

Adashi EY：“小鼠卵巢内胰岛素样生长因子 1 系统：偏离大鼠范例。”

MATSUMOTO T: "Increased levels of IGF-I and IGFBP-3 in synovial fluids of patients with rheumatoid arthritis." Endocrine Journal. 45. s141-144 (1998)

MATSUMOTO T：“类风湿关节炎患者滑液中 IGF-I 和 IGFBP-3 的水平升高。”

Matsumoto T: "Effects of interleukin-1β on insulin-like growth factor-I autocrine/paracrine axis in cultured rat articular chondrocytes." Annals of Rheumatic Diseases. 53. 128-133 (1994)

Matsumoto T：“白介素-1β 对培养的大鼠关节软骨细胞中胰岛素样生长因子-I 自分泌/旁分泌轴的影响。”风湿病年鉴 53. 128-133 (1994)

Matsumoto T,: "Increased levels of IGF-I and IGFBP-3 in synoyial fluids of patients with rheumatoid arthritis." Endocrine Journal. 45. S141-S144 (1998)

Matsumoto T：“类风湿性关节炎患者滑液中 IGF-I 和 IGFBP-3 的水平升高。”

Matsumoto T: "Identification and characterization of insulin-like growth factors (IGFs),IGFBPs and IGFBP proteases in human synovial fluid." Journal of Clinical Endocrinology and Metabolism. 81. 150-155 (1996)

Matsumoto T：“人类滑液中胰岛素样生长因子 (IGF)、IGFBP 和 IGFBP 蛋白酶的鉴定和表征。”