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Analysis of molecular mechanism on the training effects using adrenergic receptor agonists

肾上腺素受体激动剂对训练效果的分子机制分析

基本信息

批准号：
15500437
负责人：
KITAURA Takashi
金额：
$ 2.43万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

In this study, we tried to examine the longitudinal inhibitory growth effects on bone of clenbuterol (beta-2 adrenergic receptor agonist) using reverse-transcription polymerase chain reaction (RT-PCR) analysis of the cultured osteoclast cells derived from mouse bone marrow cells with calcitriol (10 nM)and dexamethasone (10 nM). During the differentiation process from preosteoclasts into the matured osteoclasts, the clenbuterol were administered into the culture system. Clenbuterol increased the number of osteoclasts. The both of tulobuterol and isoproterenol also increased the osteoclasts. But the selective beta-2 antagonist (butoxamine) and H89 (protein kinase A inhibitor) inhibited the increased osteoclasts. It suggested the increased osteoclasts might be induced by the increased cAMP.It is well known that the PGE2 accelerate the forming of osteoclasts. The mRNA expression of COX-2 which is PGE2 synthetase also increased with the treatments of clenbuterol, turobuterol, and isoproterenol. Furthermore, the mRNA expression of bone resorptive cytokines, IL-1β and IL-6 were increased by clenbuterol, which also accelerated the bone forming by the osteoblasts activation... These results suggested that this clenbuterol affected more strongly on osteoclast forming system but a little on osteoblast. It means that these drugs have the activating action on various cells but the whole effects are complicated. Therefore, the using of these drugs should be careful.We confirmed that clenbuterol increased the expression of mRNAs of UCP3 which increases lipolysis and MyoD which is nuclear regulatory factor. They suggested that clenbuterol increased the MyoD as the myogenic master regulator and might induce the muscle hypertrophy and the transformation from slow-to fast-twitch muscle.

本研究利用骨化三醇（10 nM）和地塞米松（10 nM）对小鼠骨髓细胞培养的破骨细胞进行逆转录聚合酶链反应（RT-PCR），研究盐酸克仑特罗（β -2肾上腺素能受体激动剂）对骨的纵向抑制生长作用。在破骨前细胞向成熟破骨细胞分化过程中，在培养体系中加入盐酸克仑特罗。盐酸克仑特罗增加了破骨细胞的数量。妥罗布特罗和异丙肾上腺素均能增加破骨细胞。但选择性β -2拮抗剂（丁胺）和H89（蛋白激酶A抑制剂）抑制了增加的破骨细胞。提示破骨细胞的增加可能是由cAMP升高引起的。众所周知，PGE2促进破骨细胞的形成。盐酸克仑特罗、妥罗布特罗和异丙肾上腺素处理后，PGE2合成酶COX-2 mRNA表达量增加。克仑特罗可提高骨吸收细胞因子、IL-1β和IL-6 mRNA的表达，并通过激活成骨细胞促进骨形成。说明盐酸克仑特罗对破骨细胞形成系统的影响较强，对成骨细胞的影响较小。这意味着这些药物对各种细胞都有激活作用，但整体效果是复杂的。因此，使用这些药物应谨慎。我们证实克仑特罗增加了UCP3 mrna的表达，增加了脂肪分解和MyoD（核调节因子）。他们认为盐酸克仑特罗作为肌生成主调节剂增加了肌od，并可能诱导肌肉肥大和由慢肌到快肌的转变。