Mannose receptor C type 2 mediates 1,25(OH)2D3/vitamin D receptor-regulated collagen metabolism through collagen type 5, alpha 2 chain and matrix metalloproteinase 13 in murine MC3T3-E1 cells

Mannose receptor C type 2 mediates 1,25(OH)2D3/vitamin D receptor-regulated collagen metabolism through collagen type 5, alpha 2 chain and matrix metalloproteinase 13 in murine MC3T3-E1 cells
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小鼠 MC3T3-E1 细胞中 2 型甘露糖受体 C 通过 5 型胶原、α2 链和基质金属蛋白酶 13 介导 1,25(OH)(2)D-3/维生素 D 受体调节的胶原代谢

DOI:
10.1016/j.mce.2019.01.007
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发表时间:
2019-03-01
影响因子:
4.1
通讯作者:
Zhao, Qun
Zhao, Qun
中科院分区:
医学2区
文献类型:
--
作者:
Dong, Yaping;Yang, Liping;Zhao, Qun

文献摘要

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维生素D在维持骨骼发育和骨稳态方面起着重要作用。虽然维生素D已被广泛研究,但1,25(OH)(2)D-3对成骨细胞的直接影响尚不清楚。为了探索1,25(OH)(2)D-3对小鼠成骨细胞的作用,我们对用和不用1,25(OH)(2)D-3处理的MC 3 T3-E1细胞进行了串联质量标签实验。本研究证实了三个与骨代谢相关的上调蛋白(MRC 2、WWTR 1和RASSF 2)。1,25(OH)(2)D-3通过维生素D受体上调MRC 2的表达。MRC 2影响成骨细胞中的胶原代谢。结合生物信息学和平行反应监测分析,通过抑制MRC 2的表达,探讨MRC 2与胶原的关系。MRC 2下调COL 5A 2的表达,上调MMP 13的表达。本研究提供了1,25(OH)(2)D-3处理的小鼠成骨细胞的蛋白质谱,揭示了一个新发现的信号传导轴(1,25(OH)(2)D-3/VDR/MRC 2/COL 5A 2和MMP 13),并从一个新的角度解释了1,25(OH)(2)D-3对骨代谢的影响。
Vitamin D plays an important role in maintaining skeletal development and bone homeostasis. Although vitamin D has been extensively researched, the direct effect of 1,25(OH)(2)D-3 on osteoblasts is unclear. To explore the 1,25(OH)(2)D-3 action on murine osteoblasts, we performed tandem mass tag experiments on MC3T3-E1 cells treated with and without 1,25(OH)(2)D-3. Three up-regulated proteins (MRC2, WWTR1 and RASSF2) related to bone metabolism were confirmed in this study. 1,25(OH)(2)D-3 up-regulated the expression of MRC2 through vitamin D receptor. MRC2 affects collagen metabolism in osteoblasts. Combined with bioinformatics and parallel reaction monitoring analysis, we inhibited the expression of MRC2 to explore the relationship between MRC2 and collagens. Then we found MRC2 down-regulated COL5A2 and up-regulated MMP13. This study provides a protein profile of 1,25(OH)(2)D-3-treated murine osteoblasts, reveals a newly discovered signaling axis (1,25(OH)(2)D-3/VDR/MRC2/COL5A2 and MMP13), and explains the effect of 1,25(OH)(2)D-3 on bone metabolism from a new perspective.