Magnesium inhibits the calcification of the extracellular matrix in tendon-derived stem cells via the ATP-P2R and mitochondrial pathways

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• 作者：Jiaji Yue^a ; ^b ; ¹ ; Shanzi Jin^a ; ^b ; ¹ ; Yaqiang Li^a ; ^b ; ¹ ; Li Zhang^a ; ^c ; Wenwei Jiang^a ; ^d ; Chunxi Yang^a ; ^{chunxi_yang@163.com" class="auth_mail" title="E-mail the corresponding author} ; Jiang Du^e ; ^{dujiang@tongji.edu.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tendon calcification ; Tendon-derived stem cells ; Magnesium ; P2 receptors ; Mitochondria
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2016
• 出版时间：9 September 2016
• 年：2016
• 卷：478
• 期：1
• 页码：314-322
• 全文大小：2385 K

文摘

Tendon calcification has been widely regarded by researchers to result from the osteogenic differentiation of Tendon-Derived Stem Cells (TDSCs) and ectopic mineralization caused by the calcification of cellular matrix. Recent studies have revealed a correlation between the Mg²⁺/Ca²⁺ balance and the degeneration or calcification of tendon tissues. Furthermore, the ATP–P2X/P2Y receptor pathway has been shown to play a decisive role in the process of calcification, with calcium exportation from mitochondria and calcium oscillations potentially representing the cohesive signal produced by this pathway. Our previous study demonstrated that matrix calcification is inhibited by magnesium. In this study, we examined the effects of extracellular Mg²⁺ on the deposition of calcium phosphate matrix and cellular pathways in TDSCs. The suppression of the export of calcium from mitochondria has also been detected. We found that a high concentration of extracellular Mg²⁺ ([Mg²⁺]_e) inhibited the mineralization of the extracellular matrix in TDSCs and that 100 μM ATP reversed this inhibitory effect in vitro. In addition, the spontaneous release of ATP was inhibited by high [Mg²⁺]_e levels. A high [Mg²⁺]_e suppressed the expression of P2X4, P2X5 and P2X7 and activated the expression of P2Y1, P2Y2, P2Y4 and P2Y14. The interaction between Mg²⁺ and Ca²⁺ is therefore contradictory, Mg²⁺ inhibits mitochondrial calcium concentrations, meanwhile it reverses the opening of mPTP that is induced by Ca²⁺. JC-1 staining verified the protective effect of Mg²⁺ on mitochondrial membrane potential and the decrease induced by Ca²⁺. Taken together, these results indicate that high [Mg²⁺]_e interferes with the expression of P2 receptors, resulting in decreased extracellular mineralization. The balance between Mg²⁺ and Ca²⁺ influences mitochondrial calcium exportation and provides another explanation for the mechanism underlying matrix calcification in TDSCs.