Sodium Benzoate Inhibits Osteoblast Differentiation and Accelerates Bone Loss by Regulating the FGF2/p38/RUNX2 Pathway

Sodium benzoate (NaB) is a commonly used food ingredient that is also found in cosmetics and medicines. Previous studies have demonstrated that long-term NaB intake has detrimental effects on human health, while its effects on bone mass remain unknown. In the present study, intragastric NaB administration was found to decrease bone mass and deteriorate bone microstructure <i>in vivo</i>, while prolonged NaB gavage further accelerated bone loss. The <i>in vitro</i> study revealed that NaB inhibited osteoblast differentiation of bone marrow mesenchymal stem cells and MC3T3-E1 cells. Mechanistically, RNA sequencing analysis elucidated that NaB greatly suppressed fibroblast growth factor 2 (FGF2) expression. Further studies revealed that NaB inhibited p38/RUNX2 signaling transduction, which was downstream of FGF2 for modulating osteoblast differentiation. The rescue studies suggested that NaB inhibited RUNX2 expression and osteoblast differentiation through the p38/MAPK signaling pathway. Collectively, NaB accelerated bone loss by inhibiting osteoblast differentiation through downregulating FGF2/p38/RUNX2 signaling pathway. The present study revealed that the long-term intake of NaB-containing food increased the risk of bone loss and osteoporosis (OP). Therefore, a reasonable oral intake of NaB-containing food is an important but convenient initiative for preventing OP.