| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Research Abstract |
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
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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
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