Global increase in O-linked N-acetylglucosamine modification promotes osteoblast differentiation
Global increase in O-linked N-acetylglucosamine modification promotes osteoblast differentiation
复制标题
DOI：
10.1016/j.yexcr.2015.08.009
复制
发表时间：
2015-11-01
影响因子：
3.7
通讯作者：
Kamemura, Kazuo
中科院分区：
文献类型：
--
作者：
Koyama, Takahiro;Kamemura, Kazuo
骨形成和骨吸收之间的平衡由成骨细胞和破骨细胞维持，这种骨代谢的失衡导致骨质疏松症。在这里，我们发现，成骨细胞分化MC 3 T3-E1细胞中的O-连接的β-N-乙酰氨基葡萄糖苷酶（O-GlcNAc酶）的失活促进和抑制O-GlcNAc转移酶的失活，如细胞外基质钙化所示。在成骨细胞分化过程中，成骨基因如alp、ocn和bsp的表达以O-GlcNAc糖基化依赖的方式受到正调控。由于已证实Etsl和Runx 2是负责这些成骨基因表达的两个关键转录因子，因此它们的转录活性可能受O-GlcNAc糖基化调节。然而，破骨细胞分化的RAW 264细胞，所示的抗酒石酸酸性磷酸酶的表达和活性，不受O-GlcNAc酶或O-GlcNAc转移酶的失活。我们的研究结果表明，操纵O-GlcNAc糖基化的方法可能有助于开发骨质疏松症的治疗方法。(C)2015 Elsevier Inc. All rights reserved.
The balance between bone formation and bone resorption is maintained by osteoblasts and osteoclasts, and an imbalance in this bone metabolism leads to osteoporosis. Here, we found that osteoblast differentiation in MC3T3-E1 cells is promoted by the inactivation of O-linked beta-N-acetylglucosaminidase (O-GlcNAcase) and suppressed by the inactivation of O-GlcNAc transferase, as indicated by extracellular matrix calcification. The expression of osteogenic genes such as alp, ocn, and bsp during osteoblast differentiation was positively regulated in a O-GlcNAc glycosylation-dependent manner. Because it was confirmed that Etsl and Runx2 are the two key transcription factors responsible for the expression of these osteogenic genes, their transcriptional activity might therefore be regulated by O-GlcNAc glycosylation. However, osteoclast differentiation of RAW264 cells, as indicated by the expression and activity of tartrate-resistant acid phosphatase, was unaffected by the inactivation of either O-GlcNAcase or O-GlcNAc transferase. Our findings suggest that an approach to manipulate O-GlcNAc glycosylation could be useful for developing the therapeutics for osteoporosis. (C) 2015 Elsevier Inc. All rights reserved.