Phosphorus-insufficient maternal milk is associated with ectopic expression of collagen I and female-specific bony changes in infant mouse cartilages

Excessive phosphorus intake causes diseases such as hyperphosphatemia and hypocalcaemia, but the effect of dietary insufficiency of phosphorus is unclear. Here, we explored the effect of phosphorus dietary insufficiency on tissue growth and maintenance by using C57BL/6J mice fed a low phosphorus diet, which contained 18.5% of the phosphorus of a normal diet. We demonstrated that the phosphorus content in the maternal milk of mother mice was significantly reduced due to the consumption of a low phosphorus diet, which further resulted in bone deformation in infant mice in a female-specific manner. Polarizing microscopic analysis of low-phosphorus milk (LPM)-induced bone deformation resulted in unusually formed crystals inside cartilage. Furthermore, immunohistochemical analysis revealed ectopic expression of collagen I in the region where crystals were ectopically formed. Electron microscopic analysis showed morphological features similar to bone tissues. Immunochemical analysis demonstrated that the amount of interleukin-6 (IL-6), a cytokine known to trigger osteoclast formation, was significantly reduced in the maternal milk of mice fed the low-phosphorus diet. Our results suggest that phosphorus intake from maternal milk is involved in infant cartilage formation.