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Role of Leptin in Endochondral Ossification

瘦素在软骨内骨化中的作用

基本信息

批准号：
13672101
负责人：
NAKANISHI Hiroaki
金额：
$ 2.3万
依托单位：
The University of Tokushima
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

项目摘要

Leptin, a 16-kDa circulating hormone is secreted mainly by white adipose tissue, It influences body weight homeostasis through its effects on food intake and energy expenditure by negative feedback at the hypothalamic nuclei. Recent studies have demonstrated that leplin is produced by other tissues, such as placenta, fetal bone/cartilage, and skeletal muscles. In addition to its effects on the central nervous system, leptin has various physiological aclions on hemalopoiesis snd ovarian function. Furthermore, other studies showed that leptin play an important physiological role in skeletogenesis. But the expression and the role of leptin in bone have not been cleared. To better understand the role of leptin in bone formation, we investigated the expression and the function of leptin in endochondral ossification.1. We invesligated immunohistochemical localization of leptin in 1-week-old mouse femurs. High expression of leptin was identified in hypertrophic chondrocyles in the vicinity of … More the neovascularzation in secondary ossification center, and osteoblasts and chondrocyles in primary spongiosa beneath the growth plate. Both MCC-5 and MC3T3-E1 were shown to produce and secrete leptin protein in vitro.2. We also delected the expression of Mrna of Ob-Rb, which was the most functional isoform in leptin receptors, in Huvec. Keprin enhanced the proliferation, chemolaxis,tube formation and the activation of MMP-2 of Huvec.3. The femur length of db/db mice is 13% shorter than of wild type mice. We observed the angiogenesis into the secondossification center in db/db mice two days later than in wild type mice.4. A right eighth rib of ICR mice was fractured. Localization of leptin at the fracture siles were investigated by immunostaining and RT-PCR. As a redult, high expression of leptin was identified in hypertrophic chondrocytes at the fracture callus. Expression level of the Mrna of leptin in the flactured rib was increased during the process of healing. Which peaked at 14 days after the fracture.5. We also compared the fracture process of mice deficient in leptin (oblob) or its receptor (db/db) and wild type mice. Interestingly, the fracture healing of ob/ob and db/db mice were later than wild type mice.These findings suggested that leptin regulated the bone formation and the fracture healing by regulating anogiogenesis in endochondral ossification. Less

瘦素是一种16 kDa的循环激素，主要由白色脂肪组织分泌，通过下丘脑核团的负反馈影响摄食和能量消耗，从而影响体重的动态平衡。最近的研究表明，Leplin是由其他组织产生的，如胎盘、胎儿骨/软骨和骨骼肌。瘦素除了对中枢神经系统有影响外，还对造血和卵巢功能具有多种生理活性。此外，其他研究表明，瘦素在骨骼形成中起着重要的生理作用。但瘦素在骨骼中的表达和作用尚不清楚。为了更好地了解瘦素在骨形成中的作用，我们研究了瘦素在软骨内成骨中的表达和功能。本文研究了瘦素在1周龄小鼠股骨中的免疫组织化学定位。瘦素在…附近肥大的软骨细胞中高表达次级骨化中心多有新生血管形成，生长板下方的原发海绵内多见成骨细胞和软骨细胞。结论：1.体外培养的MCC-5和MC3T3-E1细胞均能产生和分泌瘦素蛋白。我们还检测了HUVEC中瘦素受体功能最强的异构体Ob-Rb的mRNA表达。可普林可促进人脐静脉内皮细胞的增殖、趋化、管状形成和基质金属蛋白酶-2的活化。Db/db小鼠的股骨长度比野生型小鼠短13%。我们观察到db/db小鼠的血管生成比野生型小鼠晚两天。ICR小鼠右侧第八根肋骨骨折。用免疫组织化学染色和RT-PCR方法研究瘦素在骨折间隙的定位。结果，在骨折骨痂处肥大的软骨细胞中有瘦素的高表达。在骨折愈合过程中，肋骨组织中瘦素基因的表达水平升高。在骨折后14天达到峰值。我们还比较了瘦素及其受体缺陷小鼠(obob/db)和野生型小鼠的骨折过程。有趣的是，ob/ob和db/db小鼠的骨折愈合时间均晚于野生型小鼠，提示瘦素通过调控软骨内成骨过程中的血管生成来调控骨形成和骨折愈合。较少