Journal
CELL BIOLOGY INTERNATIONAL
Volume 42, Issue 2, Pages 205-215Publisher
WILEY
DOI: 10.1002/cbin.10888
Keywords
autophagy; magnesium; matrix vesicles; mitochondria
Categories
Funding
- National Natural Science Foundation of China [81101344/HO604]
- Outstanding Young Talent-training Plan of Tenth People's Hospital, Shanghai TongJi University School of Medicine [11RQ104]
- Climb Talent-training plan of Tenth People's Hospital, Shanghai Tongji University School of Medicine [04.01.13023]
- Fundamental Research Funds for the Central Universities [1501219095]
- Shanghai Municipal Science and Technology Commission guidance project [16411971700]
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Magnesium, as a physiological calcium antagonist, plays a vital role in the bone metabolism and the balance between magnesium and calcium is crucial in bone physiology. We recently demonstrated that matrix mineralization in human bone marrow-derived mesenchymal stem cells (hBMSCs) can be suppressed by high Mg2+. However, a complete understanding of the mechanisms involved still remains to be elucidated. As mitochondrial calcium phosphate granules depletion manifests concurrently with the appearance of matrix vesicles (MVs) and autophagy are associated with matrix mineralization, we studied the effect of high extracellular Mg2+ on these pathways. Our results first demonstrated that high Mg2+ has a significant inhibitory effect on the generalization of extracellular mineral aggregates and the expression of collagen 1 along which the mineral crystals grow. Transmission electron microscope results showed that less amount of MVs were observed inside hBMSCs treated with high Mg2+ and high Mg2+ inhibited the release of MVs. In addition, high Mg2+ significantly suppressed mitochondrial Ca2+ accumulation. Autophagy is promoted as a response to osteogenesis of hBMSCs. High Mg2+ inhibited the level of autophagy upon osteogenesis and autophagy inhibitor 3-MA significantly suppressed mineralization. Exogenous ATP can reverse the inhibitory effect of high Mg2+ by increasing the level of autophagy. Taken together, our results indicate that high Mg2+ may modulate MVs-mediated mineralization via suppressing mitochondrial Ca2+ intensity and regulates autophagy of hBMSCs upon osteogenesis, resulting in decreased extracellular mineralized matrix deposition. Our results contribute to the understanding of the role of magnesium homeostasis in osteoporosis and the design of magnesium alloys.
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