Cirmanová V, Bayer M, Stárka L, Zajíčková K
Institute of Endocrinology, Prague, Czech Republic.
Physiol Res. 2008;57 Suppl 1:S143-S151. doi: 10.33549/physiolres.931499. Epub 2008 Feb 13.
Leptin, a cytokine-like hormone secreted by adipocytes, is known to regulate food intake but has also emerged as a significant factor in the regulation of bone mass. In humans, states of energy deprivation with low serum leptin have been associated with low bone mass. In mice, leptin deficiency led to increased trabecular bone mass with overall decrease in cortical bone. Leptin regulates bone metabolism indirectly in the hypothalamus thereby activating the sympathetic nervous system (SNS). In addition to the SNS, leptin also interacts with various hypothalamic neuropeptides, such as cocaine- and amphetamine-regulated transcript, neuropeptide Y and/or neuromedin U, which might modulate the effects of leptin on bone. In osteoblasts sympathetic signaling is further gated by the transcriptional factors called molecular clock. As a result, bone loss is accelerated showing that the central effect of leptin seems to be antiosteogenic. Additionally, leptin has a direct anabolic effect within the bone driving the differentiation of bone marrow stem cells into the osteoblastic cell lineage. Besides the interaction between the central and peripheral pathways, the overall effect of leptin on bone might be bimodal depending on leptin serum concentrations. Regulatory pathways triggering osteoblast activity might open new possibilities for anabolic treatment of osteoporosis.
瘦素是一种由脂肪细胞分泌的细胞因子样激素，已知其可调节食物摄入，但也已成为骨量调节中的一个重要因素。在人类中，血清瘦素水平低的能量剥夺状态与低骨量有关。在小鼠中，瘦素缺乏导致小梁骨量增加，皮质骨总体减少。瘦素在下丘脑间接调节骨代谢，从而激活交感神经系统（SNS）。除了交感神经系统，瘦素还与各种下丘脑神经肽相互作用，如可卡因和苯丙胺调节转录物、神经肽Y和/或神经调节肽U，它们可能调节瘦素对骨骼的影响。在成骨细胞中，交感信号进一步由称为分子钟的转录因子控制。结果，骨质流失加速，表明瘦素的中枢作用似乎是抗成骨的。此外，瘦素在骨内具有直接的合成代谢作用，促使骨髓干细胞分化为成骨细胞谱系。除了中枢和外周途径之间的相互作用外，瘦素对骨骼的总体作用可能因瘦素血清浓度而异，呈双峰模式。触发成骨细胞活性的调节途径可能为骨质疏松症的合成代谢治疗开辟新的可能性。
