Maternal high protein‑diet programs impairment of offspring’s bone mass through miR‑24‑1‑5p mediated targeting of SMAD5 in osteoblasts.

Maternal nutrition is crucial for the offspring’s skeleton development and the onset of osteoporosis later in life. While
maternal low protein diet has been shown to regulate bone mass negatively, the effect of a high protein diet (HP) remains
unexplored. Here, we found that C57BL/6 mice fed with HP delivered offspring with decreased skeletal mineralization at
birth and reduced bone mass throughout their life due to a decline in their osteoblast maturation. A small RNA sequencing
study revealed that miR-24-1-5p was highly upregulated in HP group osteoblasts. Target prediction and validation studies
identified SMAD-5 as a direct target of miR-24-1-5p. Furthermore, mimic and inhibitor studies showed a negative correlation
between miR-24-1-5p expression and osteoblast function. Moreover, ex vivo inhibition of miR-24-1-5p reversed the
reduced maturation and SMAD-5 expression in the HP group osteoblasts. Together, we show that maternal HP diminishes
the bone mass of the offspring through miR-24-1-5p.