Ghrelin directly regulates bone formation
Ghrelin directly regulates bone formation
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DOI：
10.1359/jbmr.041237
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发表时间：
2005-05-01
影响因子：
6.2
通讯作者：
Kojima, M
中科院分区：
文献类型：
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作者：
Fukushima, N;Hanada, R;Kojima, M
为了阐明ghrelin在骨代谢中的作用，我们在体外和体内研究了ghrelin的作用。Ghrelin及其受体GHS-R1a在成骨细胞中被鉴定，Ghrelin促进增殖和分化。此外，ghrelin增加大鼠的BMD。Ghrelin是一种肠肽，参与生长激素（GH）的分泌和能量平衡。最近，据报道，脂肪细胞衍生的激素瘦素，它也调节能量稳态，并在能量稳态中对抗生长激素释放肽的作用，在骨代谢中起着重要作用。这一证据表明，生长激素释放肽可能调节骨代谢，但它还没有得到澄清。为了研究生长素释放肽在骨骼完整性中的作用，我们研究了其在体外和体内对骨代谢的影响。材料和方法：我们用RT-PCR和免疫组织化学（IHC）检测大鼠成骨细胞中生长素释放肽和生长激素促分泌素受体1a（GHS-R1a）的表达。通过记录细胞数量和DNA合成水平的变化来检查ghrelin对原代成骨样细胞增殖的影响。使用定量RT-PCR分析成骨细胞分化标志物（Runx 2、I型胶原α 1 [COLI]、碱性磷酸酶[ALP]、骨钙素[OCN]）。我们还检测了生长素释放肽诱导的成骨样细胞中的钙积累和ALP活性。最后，为了探讨Ghrelin对骨代谢的影响，我们检测了SD大鼠和GH缺陷型自发性侏儒大鼠（SDR）的骨密度。Ghrelin以剂量依赖性方式显著增加成骨样细胞数量和DNA合成。GHS-R1a拮抗剂[D-LyS（3）]-GHRP-6可抑制Ghrelin的促增殖作用，并呈剂量依赖性。此外，ghrelin增加成骨细胞分化标志物的表达，ALP活性和基质中的钙积累。最后，ghrelin肯定增加了SD大鼠和SDRs.Conclusions的BMD：这些观察表明，ghrelin直接刺激骨形成。
To clarify the role of ghrelin in bone metabolism, we examined the effect of ghrelin in vitro and in vivo. Ghrelin and its receptor, GHS-R1a, were identified in osteoblasts, and ghrelin promoted both proliferation and differentiation. Furthermore, ghrelin increased BMD in rats. Our results show that ghrelin directly affects bone formation.Introduction: Ghrelin is a gut peptide involved in growth hormone (GH) secretion and energy homeostasis. Recently, it has been reported that the adipocyte-derived hormone leptin, which also regulates energy homeostasis and opposes ghrelin's actions in energy homeostasis, plays a significant role in bone metabolism. This evidence implies that ghrelin may modulate bone metabolism; however, it has not been clarified. To study the role of ghrelin in skeletal integrity, we examined its effects on bone metabolism both in vitro and in vivo.Materials and Methods: We measured the expression of ghrelin and growth hormone secretagogue receptor la (GHS-R1a) in rat osteoblasts using RT-PCR and immunohistochemistry (IHC). The effect of ghrelin on primary osteoblast-like cell proliferation was examined by recording changes in cell number and the level of DNA synthesis. Osteoblast differentiation markers (Runx2, collagen alpha 1 type I [COLI], alkaline phosphatase [ALP], osteocalcin [OCN]) were analyzed using quantitative RT-PCR. We also examined calcium accumulation and ALP activity in osteoblast-like cells induced by ghrelin. Finally, to address the in vivo effects of ghrelin on bone metabolism, we examined the BMD of Sprague-Dawley (SD) rats and genetically GH-deficient, spontaneous dwarf rats (SDR).Results: Ghrelin and GHS-R1a were identified in osteoblast-like cells. Ghrelin significantly increased osteoblast-like cell numbers and DNA synthesis in a dose-dependent manner. The proliferative effects of ghrelin were suppressed by [D-LyS(3)] -GHRP-6, an antagonist of GHS-R1a, in a dose-dependent manner. Furthermore, ghrelin increased the expression of osteoblast differentiation markers, ALP activity, and calcium accumulation in the matrix. Finally, ghrelin definitely increased BMD of both SD rats and SDRs.Conclusions: These observations show that ghrelin directly stimulates bone formation.