Dual Function of Magnesium in Bone Biomineralization

Magnesium (Mg 2+ ), as a main component of bone, is widely applied to promote bone growth and regeneration. However, Mg 2+ can chemically inhibit the crystallization of amorphous calcium phosphate into hydroxyapatite (HA). The underlying mechanisms by which Mg 2+ improves bone biomineralization remain elusive. Here, it is demonstrated that Mg 2+ plays dual roles in bone biomineralization from a developmental perspective. During embryonic development, the Mg 2+ 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 2+ can promote the mineralization of bone marrow mesenchymal stem cells, while excessive Mg 2+ impairs their osteogenesis. The earlier the Mg 2+ is added, the stronger the observed inhibition of mineralization. In particular, less Mg 2+ is present in fully mineralized collagen than in poorly mineralized collagen. Furthermore, a high concentration of Mg 2+ changes the crystalline morphology of HA and inhibits collagen calcification. Functionally, a high‐Mg 2+ diet inhibits bone biomineralization in mouse offspring. Taken together, the results suggest that appropriate regulation of Mg 2+ concentration over time is vital for normal biomineralization. This study is significant for the future design of bone substitutes and implants associated with Mg 2+ content.