Department of Health Sciences, University "Magna Græcia" of Catanzaro, Viale Europa (Località Germaneto), 88100, Catanzaro, Italy.
Laboratory of Molecular Genetics, The Institute of Medical Science, University of Tokyo, 108-8639, Tokyo, Japan.
Endocrine. 2018 Mar;59(3):622-632. doi: 10.1007/s12020-017-1396-0. Epub 2017 Sep 2.
In the last few years, bone has been recognized as an endocrine organ that modulates glucose metabolism by secretion of osteocalcin, an osteoblast-specific hormone, that influences fat deposition and blood sugar levels. To date, however, very few in vitro models have been developed to investigate, at the molecular levels, the relationship between glucose, insulin and osteocalcin. This study aims at covering this gap.
We studied osteogenic differentiation, osteocalcin gene expression, and osteblast-mediated insulin secretion, using cultured MG-63 human osteoblast-like cells that underwent glucotoxicity and insulin resistance. In addition, we investigated whether a correlation existed between hyperglycemia and/or insulin resistance and total osteocalcin serum concentrations in patients.
While insulin and low glucose increased osteocalcin gene expression, disruption of insulin signaling in MG-63 osteoblasts and high glucose concentration in cell culture medium decreased osteocalcin gene transcription and reduced osteogenic differentiation. Concomitantly, insulin secretion was significantly impaired in rat INS-1 β-cells treated with conditioned medium from insulin resistant MG-63 cells or cells exposed to high glucose concentrations. Also, chronic hyperglycemia, but not insulin resistance, inversely correlated with circulating osteocalcin levels in patients.
Our results further support the existence of an endocrine axis between bone, where osteocalcin is produced, and pancreatic β-cells, and add new insights into the molecular details of this relationship. These findings may contribute to the understanding of osteocalcin regulation and its role in metabolism.
在过去的几年中，骨骼已被确认为一种内分泌器官，通过分泌成骨细胞特异性激素骨钙素来调节葡萄糖代谢，从而影响脂肪沉积和血糖水平。然而，迄今为止，很少有体外模型被开发出来，以在分子水平上研究葡萄糖、胰岛素和骨钙素之间的关系。本研究旨在填补这一空白。
我们使用经历糖毒性和胰岛素抵抗的培养的 MG-63 人成骨样细胞，研究成骨分化、骨钙素基因表达和成骨细胞介导的胰岛素分泌。此外，我们还研究了高血糖和/或胰岛素抵抗与患者血清总骨钙素浓度之间是否存在相关性。
虽然胰岛素和低血糖增加了骨钙素基因的表达，但在 MG-63 成骨细胞中破坏胰岛素信号和在细胞培养基中高葡萄糖浓度降低了骨钙素基因的转录并减少了成骨分化。同时，用来自胰岛素抵抗的 MG-63 细胞或暴露于高葡萄糖浓度的细胞的条件培养基处理的大鼠 INS-1β细胞的胰岛素分泌显著受损。此外，在患者中，慢性高血糖，但不是胰岛素抵抗，与循环骨钙素水平呈负相关。
我们的结果进一步支持骨骼（产生骨钙素的地方）和胰腺β细胞之间存在内分泌轴，并为这种关系的分子细节提供了新的见解。这些发现可能有助于理解骨钙素的调节及其在代谢中的作用。
