Cardinali Daniel P, Ladizesky Marta G, Boggio Verónica, Cutrera Rodolfo A, Mautalen Carlos
Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
J Pineal Res. 2003 Mar;34(2):81-7. doi: 10.1034/j.1600-079x.2003.00028.x.
Bone formation proceeds through a remodeling process that runs continuously, involving the resorption of old bone by osteoclasts, and the subsequent formation of new bone by osteoblasts. This is controlled by growth factors and cytokines produced in bone marrow microenvironment and by the action of systemic hormones, like parathyroid hormone, estradiol or growth hormone (GH). One candidate for hormonal modulation of osteoblast and osteoclast formation is melatonin. Because circulating melatonin declines with age, its possible involvement in post-menopausal and senescence osteoporosis is considered. This review article discusses early studies on melatonin-bone relationships and recent data that suggest a direct effect of melatonin on bone. Melatonin could act as an autacoid in bone cells as it is present in high quantities in bone marrow, where precursors of bone cells are located. Melatonin dose-dependently augmented proteins that are incorporated into the bone matrix, like procollagen type I c-peptide. Osteoprotegerin, an osteoblastic protein that inhibits the differentiation of osteoclasts is also augmented by melatonin in vitro. Another possible target cell for melatonin is the osteoclast, which degrades bone partly by generating free radicals. Melatonin through its free radical scavenger and antioxidant properties may impair osteoclast activity and bone resorption. At least in one study melatonin was both inhibitory to osteoclastic and osteoblastic cells. Therefore, the documented bone-protecting effect of melatonin in ovariectomized rats can depend in part on the free radical scavenging properties of melatonin. Additionally, melatonin may impair development of osteopenia associated with senescence by improving non-rapid eye movement sleep and restoring GH secretion. Whether melatonin can be used as a novel mode of therapy for augmenting bone mass in diseases deserves to be studied.
骨形成通过一个持续进行的重塑过程来实现，该过程涉及破骨细胞对旧骨的吸收，以及随后成骨细胞形成新骨。这一过程受骨髓微环境中产生的生长因子和细胞因子以及全身性激素（如甲状旁腺激素、雌二醇或生长激素）的作用控制。褪黑素是一种可能对成骨细胞和破骨细胞形成起激素调节作用的物质。由于循环中的褪黑素会随着年龄增长而下降，因此人们认为它可能与绝经后骨质疏松症和衰老性骨质疏松症有关。这篇综述文章讨论了关于褪黑素与骨骼关系的早期研究以及表明褪黑素对骨骼有直接作用的最新数据。褪黑素在骨髓（骨细胞前体所在的部位）中大量存在，因此它可能作为一种自分泌物质在骨细胞中发挥作用。褪黑素能剂量依赖性地增加掺入骨基质的蛋白质，如I型前胶原c肽。骨保护素是一种抑制破骨细胞分化的成骨细胞蛋白，在体外也会因褪黑素而增加。褪黑素的另一个可能的靶细胞是破骨细胞，破骨细胞通过产生自由基部分地降解骨骼。褪黑素凭借其自由基清除剂和抗氧化特性可能会损害破骨细胞活性和骨吸收。至少在一项研究中，褪黑素对破骨细胞和成骨细胞都有抑制作用。因此，褪黑素在去卵巢大鼠中已被证明的骨骼保护作用可能部分取决于褪黑素的自由基清除特性。此外，褪黑素可能通过改善非快速眼动睡眠和恢复生长激素分泌来减轻与衰老相关的骨质减少的发展。褪黑素是否可作为一种增加疾病中骨量的新型治疗方式值得研究。
