2. Academic Validation
  3. Salvianolic acid A promotes bone-fracture healing via balancing osteoblast and osteoclast differentiation

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

  • FASEB J. 2025 Jan 31;39(2):e70364. doi: 10.1096/fj.202402515R.
Binhao Cao 1 2 3 4,  Xiaoyong Wu 1 2 3 4,  Chengwei Zhou 1 2 3 4,  Hongyu Chen 1 2 3 4,  Deting Xue 1 2 3 4,  Zhijun Pan 1 2 3 4
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
  • 2 Orthopedics Research Institute of Zhejiang University, Hangzhou, People's Republic of China.
  • 3 Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, People's Republic of China.
  • 4 Clinical Research Center of Motor System Disease of Zhejiang Province, Hangzhou, People's Republic of China.
PMID: 39878631 DOI: 10.1096/fj.202402515R
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.

Keywords

BMSCs; Notch1; bone‐fracture healing; osteoclasts; osteogenesis; salvianolic acid A.

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