Role of Melastatin Transient Receptor Potential 7 Channels in the Osteoblastic Differentiation of Murine MC3T3 Cells
Role of Melastatin Transient Receptor Potential 7 Channels in the Osteoblastic Differentiation of Murine MC3T3 Cells
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DOI：
10.1007/s00223-010-9455-z
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发表时间：
2011-03-01
影响因子：
4.2
通讯作者：
Moreau, Robert
中科院分区：
文献类型：
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作者：
Abed, Elie;Martineau, Corine;Moreau, Robert
成骨细胞的协调增殖、迁移、分化和分泌功能确保了足够的骨形成。流行病学研究已将膳食镁（Mg）摄入不足与骨质疏松症联系起来。在这里，我们研究了melastatin样瞬时受体电位7（TRPM 7），钙（Ca）和镁通道，在小鼠MC 3 T3细胞系的成骨细胞分化的作用。通过碱性磷酸酶活性、骨钙素基因表达和细胞外基质矿化监测成骨细胞分化。TRPM 7的基因表达随着成骨细胞分化而增加，表明细胞内Ca/Mg稳态对细胞分化的重要性。细胞内Ca/Mg稳态的改变，低细胞外Ca或Mg的培养条件显着降低成骨细胞分化标志物碱性磷酸酶活性和骨钙素基因表达。根据，基质矿化降低细胞外低钙或镁水平。然而，表达的胶原蛋白I型，主要的基质蛋白，在低镁培养条件下增加，表明基质蛋白生产功能障碍不能占减少矿化。在分化期间沉默TRPM 7表达也降低了成骨细胞分化和基质矿化的程度。成骨细胞转录因子Runx 2的基因表达降低的条件下，低细胞外钙或镁水平的培养，以及TRPM 7沉默。我们的研究结果表明，细胞内钙和镁稳态TRPM 7的表达是确保MC 3 T3细胞的成骨细胞分化的重要。因此，镁缺乏症是人群中常见的疾病，可能与成骨细胞分化改变有关，导致骨形成不足和骨质疏松症的发生。
Adequate bone formation is assured by the coordinated proliferation, migration, differentiation, and secretory functions of osteoblasts. Epidemiological studies have linked insufficient dietary magnesium (Mg) intake to osteoporosis. Here, we investigated the role of melastatin-like transient receptor potential 7 (TRPM7), a calcium (Ca) and Mg channel, in osteoblastic differentiation of the murine MC3T3 cell line. Osteoblastic differentiation was monitored by alkaline phosphatase activity, osteocalcin gene expression, and extracellular matrix mineralization. Gene expression of TRPM7 increased with osteoblastic differentiation, suggesting the importance of intracellular Ca/Mg homeostasis to cell differentiation. Alteration of intracellular Ca/Mg homeostasis by culture conditions with low extracellular Ca or Mg significantly reduced the osteoblastic differentiation markers alkaline phosphatase activity and osteocalcin gene expression. In accordance, matrix mineralization was reduced under low extracellular Ca or Mg levels. Nevertheless, expression of collagen type I, the predominant matrix protein, was increased in low-Mg culture conditions, indicating that dysfunction of matrix protein production cannot account for the reduced mineralization. Silencing TRPM7 expression during the differentiation period also reduced osteoblastic differentiation and the extent of matrix mineralization. Gene expression of osteoblastic transcription factor Runx2 was reduced by conditions of culture under low extracellular Ca or Mg levels, as well as by TRPM7 silencing. Our results indicate that intracellular Ca and Mg homeostasis ensured by TRPM7 expression is important for the osteoblastic differentiation of MC3T3 cells. Thus, Mg deficiency, a common condition among the population, may be associated with altered osteoblastic differentiation leading to inadequate bone formation and the development of osteoporosis.