During the last decade, the disclosure of systemic effects of osteocalcin (OCN) in its undercarboxylated form contributed to switch the concept of bone from a merely structural apparatus to a fully endocrine organ involved in the regulation of systemic functions. Since that time, the role of OCN as osteokine has been more and more widened appreciated and detailed by the major use of animal models, starting from the original function in the bone extracellular matrix as Gla-protein and spanning from the protective effects towards weight gain, insulin sensitivity and glucose homeostasis, to the anabolic and metabolic roles in skeletal muscle, to the stimulating effects on the testis endocrine function and male fertility, to the most recent preservation from anxious and depressive states through a direct activity on the central nervous system. In this review, experimental data supporting the inter-organ communication roles of this protein are discussed, together with the available data supporting the consistency between experimental data obtained in animals and those reported in humans. In addition, a specific session has been devoted to the possible significance the OCN as a template agonist on its receptor GPRC6A, for the development of novel therapeutic and pharmacological approaches for the treatment of dismetabolic states and male infertility.

在过去的十年中，骨钙蛋白（OCN）的羧基不足形式的全身作用的披露有助于将骨骼的概念从单纯的结构器械转变为参与调节全身功能的内分泌器官。从那时起，OCN作为骨因子的作用已被动物模型的主要用途越来越广泛地理解和详述，从骨细胞外基质中最初的功能（如Gla蛋白）开始，从保护作用到体重增加胰岛素敏感性和葡萄糖稳态，对骨骼肌的合成代谢和代谢作用，对睾丸内分泌功能和男性生育力的刺激作用，以及通过对中枢神经系统的直接活动而从焦虑和抑郁状态得到的最新保护。在这篇综述中，讨论了支持该蛋白质的器官间通讯作用的实验数据，以及支持在动物中获得的实验数据与人类报告的实验数据之间一致性的可用数据。此外，专门的会议专门讨论了OCN作为其受体GPRC6A的模板激动剂的可能意义，对于开发治疗代谢异常和男性不育的新型治疗和药理方法可能具有的意义。