Salvianolic acid A promotes bone‐fracture healing via balancing osteoblast and osteoclast differentiation

Abstract Nonunion is a significant complication in fracture management for surgeons. Salvianolic acid A (SAA), derived from the traditional Chinese plant Salviae miltiorrhizae Bunge (Danshen), exhibits notable anti‐inflammatory and antioxidant properties. Although studies have demonstrated its ability to promote osteogenic differentiation, the exact mechanism of action remains unclear. This study investigated the effects of various SAA concentrations on the osteogenic differentiation of mouse‐derived bone marrow mesenchymal stem cells (mBMSCs) and the osteoclastic differentiation of bone marrow‐derived macrophages. Our findings indicate that SAA promotes the osteogenic differentiation of mBMSCs in a concentration‐dependent manner, primarily by inhibiting the Notch1 signaling pathway. Notably, the administration of two Notch1 agonists (Jagged‐1 and VPA) inhibited the effects of SAA on osteogenic differentiation. Additionally, SAA facilitated the autophagic degradation of NICD1, further enhancing osteogenic differentiation. Furthermore, SAA also dose‐dependently inhibited the osteoclastic differentiation of bone marrow‐derived macrophages, which is linked to its suppression of NF‐κB signaling pathways. In a fracture model, SAA demonstrated a capacity to promote healing. In conclusion, SAA enhances bone fracture healing by balancing osteoblast and osteoclast differentiation.