Dual Function of Magnesium in Bone Biomineralization.

Magnesium (Mg ), as a main component of bone, is widely applied to promote bone growth and regeneration. However, Mg can chemically inhibit the crystallization of amorphous calcium phosphate into hydroxyapatite (HA). The underlying mechanisms by which Mg improves bone biomineralization remain elusive. Here, it is demonstrated that Mg plays dual roles in bone biomineralization from a developmental perspective. During embryonic development, the Mg concentration is enriched in the early stage from embryonic day 13.5 (E13.5) to E15.5, but gradually decreases to a stable state in the late phase, after E15.5. Appropriate concentrations of Mg can promote the mineralization of bone marrow mesenchymal stem cells, while excessive Mg impairs their osteogenesis. The earlier the Mg is added, the stronger the observed inhibition of mineralization. In particular, less Mg is present in fully mineralized collagen than in poorly mineralized collagen. Furthermore, a high concentration of Mg changes the crystalline morphology of HA and inhibits collagen calcification. Functionally, a high-Mg diet inhibits bone biomineralization in mouse offspring. Taken together, the results suggest that appropriate regulation of Mg concentration over time is vital for normal biomineralization. This study is significant for the future design of bone substitutes and implants associated with Mg content.