Dual Function of Magnesium in Bone Biomineralization.

Magnesium (Mg2+), as a main component of bone, is widely applied to promote bone growth and regeneration. However, Mg2+ can chemically inhibit the crystallization of amorphous calcium phosphate into hydroxyapatite (HA). The underlying mechanisms by which Mg2+ improves bone biomineralization remain elusive. Here, it is demonstrated that Mg2+ plays dual roles in bone biomineralization from a developmental perspective. During embryonic development, the Mg2+ 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 Mg2+ can promote the mineralization of bone marrow mesenchymal stem cells, while excessive Mg2+ impairs their osteogenesis. The earlier the Mg2+ is added, the stronger the observed inhibition of mineralization. In particular, less Mg2+ is present in fully mineralized collagen than in poorly mineralized collagen. Furthermore, a high concentration of Mg2+ changes the crystalline morphology of HA and inhibits collagen calcification. Functionally, a high-Mg2+ diet inhibits bone biomineralization in mouse offspring. Taken together, the results suggest that appropriate regulation of Mg2+ concentration over time is vital for normal biomineralization. This study is significant for the future design of bone substitutes and implants associated with Mg2+ content.