Leptin synergizes with thyroid hormone signaling in promoting growth plate chondrocyte proliferation and terminal differentiation in vitro.
Leptin synergizes with thyroid hormone signaling in promoting growth plate chondrocyte proliferation and terminal differentiation in vitro.
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DOI：
10.1016/j.bone.2011.02.012
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发表时间：
2011-05
期刊：
影响因子：
4.1
通讯作者：
Lai Wang;Yvonne Y. Shao;R. T. Ballock
中科院分区：
文献类型：
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作者：
Lai Wang;Yvonne Y. Shao;R. T. Ballock
瘦素和甲状腺激素是两种通过中央信号机制调节能量平衡的激素。最近对瘦素缺陷型 ob/ob 小鼠的研究表明，瘦素在调节生长板功能方面也具有外周效应，可能是在增殖和分化增强方面。甲状腺激素已被充分描述为生长板软骨细胞成熟的有效刺激剂。因此，本研究的目的是研究瘦素和甲状腺激素信号在生长板软骨细胞增殖和终末分化中的相互作用。我们的体外数据表明，瘦素通过激活 IGF-1/IGF1R 信号传导和 Wnt/β-catenin 信号传导与甲状腺激素发挥协同作用，这两条途径先前被描述为甲状腺激素作用的下游效应器。瘦素增加甲状腺激素受体-α (TRα) 表达和甲状腺激素受体转录活性。甲状腺激素还会激活正在增殖和肥大的生长板细胞中的瘦素信号传导。我们得出结论，瘦素与甲状腺激素协同相互作用，促进生长板软骨细胞增殖和终末分化。
Leptin and thyroid hormone are two hormones that regulate energy balance through central signaling mechanisms. Recent studies in leptin-deficient ob/ob mice indicate that leptin also has peripheral effects in modulating the function of the growth plate, perhaps in terms of proliferation and differentiation enhancement. Thyroid hormone has been well-described as a potent stimulator of growth plate chondrocyte maturation. The objective of this study was therefore to investigate the interaction between leptin and thyroid hormone signaling in growth plate chondrocyte proliferation and terminal differentiation. Our in vitro data demonstrate that leptin synergistically functions with thyroid hormone through activation of both IGF-1/IGF1R signaling and Wnt/β-catenin signaling, two pathways that have been previously described as downstream effectors of thyroid hormone action. Leptin increases thyroid hormone receptor-α (TRα) expression and thyroid hormone receptor transcriptional activity. Thyroid hormone also activates leptin signaling in growth plate cells undergoing proliferation and hypertrophy. We conclude that leptin synergically interacts with thyroid hormone in promoting growth plate chondrocyte proliferation and terminal differentiation.