Dmp1Cre -directed knockdown of PTHrP in murine decidua is associated with increased bone width and a life-long increase in strength specific to male progeny

Parathyroid hormone related-protein (PTHrP) is a pleiotropic regulator of tissue homeostasis. In bone, knockdown in osteocytes by targeted deletion causes osteopenia and impaired strength. We report that this outcome depends on parental genotype. Adult mice from homozygous parents () have stronger bones, with 40% more trabecular bone mass and 30% greater femoral width than controls. At 12 days old, greater bone width was also found in male and female mice, but not in gene-matched mice from heterozygous parents, suggesting a maternal influence before weaning. Milk PTHrP levels were normal, but decidua from mothers of mice were smaller, with low PTHrP levels. Moreover, embryonic bone was more mineralized and wider than control. We conclude that leads to gene recombination in decidua, and that decidual PTHrP influences decidual cell maturation and limits embryonic bone growth. This identifies a maternal-derived developmental origin of adult bone strength.