ROLE OF CYTOKINES IN THYROXIN-STIMULATED BONE LOSS

细胞因子在甲状腺素刺激的骨丢失中的作用

• 批准号: 3246787
• 负责人: PAULA H STERN
• 金额: $ 9.01万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3246787
• 关键词: bioassay; cytokine; cytokine receptors; enzyme mechanism; fatty acid biosynthesis; hormone regulation /control mechanism; insulinlike growth factor; interleukin 1; interleukin 6; iodotyrosine; laboratory rat; messenger RNA; neutralizing antibody; osteocalcin; osteoclasts; osteoporosis; physiologic bone resorption; prostaglandin endoperoxide synthase; protein biosynthesis; radioimmunoassay; secretory protein; thyroxine; tissue /cell culture; transforming growth factors; triiodothyronine; tumor necrosis factor alpha

Excess thyroid hormone is a significant cause of secondary osteoporosis. Although it is well established that thyroid hormones have a direct effect, on bone to increase resorption, the mechanism of the effect has not been fully elucidated. Thyroid hormones do not produce complete resorption in vitro. Also, their effects are biphasic. Interactions of thyroid hormones with the immune system and the effects of immunosuppressive agents to inhibit thyroid hormone-stimulated bone resorption suggest that cytokines might mediate or modulate thyroid hormone action on bone. To investigate, this further, we will determine the effects of thyroid hormones on the secretion of certain cytokines in cultures of fetal rat limb bones and UMR- 106 osteoblastic osteosarcoma cells. IL-1alpha and beta, IL-6, TNFalpha, TGFbeta and IGF-I local factors that affect bone metabolism will be measured in cultures incubated with thyroxine, triiodothyronine and with the inactive analogs, reverse triiodothyronine or diiodotyrosine. Effects of available neutralizing antibodies and the interleukin receptor antagonist protein on the action of thyroid hormones to stimulate resorption (in the cultures) and osteocalcin production (in the cells) will be determined. Since thyroid hormones stimulate prostaglandin production in some tissues, cyclooxygenase inhibitors will be used to assess the relationship of prostaglandin production to the secretion of the local factors. Studies on thyroid hormone effects on mRNA for cytokines identified as possible mediators will be initiated.

甲状腺激素过多是继发性骨质疏松症的重要原因。 尽管甲状腺激素具有直接作用，但已很好地确定 关于增加吸收的骨骼，效果的机制尚未 完全阐明。 甲状腺激素不会在 体外。 而且，它们的作用是双相。甲状腺激素的相互作用 与免疫系统以及免疫抑制剂对 抑制甲状腺激素刺激的骨吸收表明细胞因子 可能介导或调节甲状腺激素对骨骼的作用。 调查， 进一步，我们将确定甲状腺激素对 在胎儿大鼠肢体和UMR的培养物中某些细胞因子的分泌 106个成骨细胞骨肉瘤细胞。 IL-1Alpha和Beta，IL-6，tnfalpha， 影响骨代谢的TGFBETA和IGF-I局部因素将是 在与甲状腺素，三碘甲醇蛋白一起孵育的培养物中测量 非活性类似物，反向三碘甲状腺素或二碘酪氨酸。 效果 可用的中和抗体和白介素受体的 拮抗剂蛋白对甲状腺激素刺激的作用 吸收（在培养物中）和骨钙素的产生（在细胞中）将 可以确定。 由于甲状腺激素刺激前列腺素产生 在某些组织中，环氧合酶抑制剂将用于评估 前列腺素生产与当地分泌的关系 因素。 研究甲状腺激素对细胞因子mRNA的影响 确定为可能的调解人。