Role of Leptin in Endochondral Ossification

瘦素是一种16 kda的循环激素，主要由白色脂肪组织分泌，它通过下丘脑核的负反馈作用影响食物摄入和能量消耗，从而影响体重稳态。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。除了对中枢神经系统的作用外，瘦素对造血和卵巢功能也有各种生理影响。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未被明确。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成骨中的表达和功能。我们研究了瘦素在1周龄小鼠股骨中的免疫组织化学定位。在继发性骨化中心附近的增生性软骨细胞，以及生长板下原发性海绵组织的成骨细胞和软骨细胞中发现瘦素的高表达。MCC-5和MC3T3-E1均能在体外产生和分泌瘦素蛋白2。我们还在Huvec中检测了Ob-Rb Mrna的表达，Ob-Rb是瘦素受体中最具功能的亚型。Keprin可促进huvec细胞增殖、趋化、成管及MMP-2的活化。db/db小鼠股骨长度比野生型小鼠短13%。我们观察到db/db小鼠血管新生进入第二骨化中心的时间比野生型小鼠晚2天。ICR小鼠右第八根肋骨骨折。采用免疫染色法和RT-PCR检测骨折裂孔中瘦素的定位。结果，瘦素在骨折愈伤组织的肥大软骨细胞中高表达。在骨折肋骨愈合过程中，瘦素Mrna表达水平升高。骨折后14天达到峰值。我们还比较了瘦素（oblob）或其受体（db/db）缺乏小鼠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比野生型小鼠晚。提示瘦素通过调节软骨内成骨过程中的骨生成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