Role of Leptin in Endochondral Ossification

瘦素是一种主要由白色脂肪组织分泌的16-kDa的循环激素，它通过下丘脑核团的负反馈作用影响食物摄入和能量消耗，从而影响体重的稳态。最近的研究表明，leplin是由其他组织，如胎盘，胎儿骨/软骨，和骨骼肌。瘦素除了对中枢神经系统的作用外，对造血和卵巢功能也有多种生理作用。此外，其他研究表明，瘦素在骨骼发生中发挥重要的生理作用。但瘦素在骨骼中的表达及其作用尚未明确。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骨化中的表达及其功能.我们研究了瘦素在1周龄小鼠股骨的免疫组织化学定位。瘦素的高表达在肥大的软骨细胞中， ...更多信息 次级骨化中心新生血管形成，生长板下初级松质骨内有成骨细胞和软骨细胞。MCC-5和MC 3 T3-E1在体外均能产生和分泌瘦素蛋白.我们还检测了瘦素受体中功能最强的亚型Ob-Rb在HUVEC中的mRNA表达。Keprin可促进HUVEC的增殖、趋化、管腔形成及MMP-2的活化. db/db小鼠的股骨长度比野生型小鼠短13%。db/db小鼠第二血管中心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。用免疫组化和RT-PCR方法检测瘦素在骨折侧骨的定位。结果显示，骨折骨痂肥大软骨细胞中瘦素表达增高。在骨折愈合过程中，瘦素mRNA的表达水平增加。其峰值出现在地震后14天。我们还比较了瘦素（oblob）或其受体（db/db）缺陷小鼠和野生型小鼠的骨折过程。ob/ob和db/db小鼠骨折愈合时间均晚于野生型小鼠，提示瘦素可能通过调节软骨内成骨过程中的骨骼发生来调节骨形成和骨折愈合。少

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