Synergistic osteogenesis and angiogenesis in promoting bone repair by levistolide A-induced smad pathway activation

Bone defects are a prevalent issue in orthopedics clinics, and tissue engineering offers a new hope for treatment. Angiogenesis ability is indispensable during the healing process of bone defects, and the combination of osteogenesis and angiogenesis ability is essential in treating bone defects effectively. Herein, with the aid of traditional Chinese medicine, we have discovered that Levistolide A, a component of Angelica sinensis, has the potential in treating bone defects due to its angiogenesis ability. In vitro experiments have demonstrated its ability to promote the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. Levistolide A can also indirectly promote the proliferation and recruitment of endothelial cells. Our proteomics analysis revealed that Levistolide A inhibited skp-1 and activated the Smad pathway to exert its effect on bone marrow mesenchymal stem cells. In vivo experiments proved that combined with a bioactive material scaffold, Levistolide A is used to effectively repair rat skull defects. Based on the above results, we have discovered a small molecule, which is cheap and stable. It can also provide hope for treatment of a large number of clinical patients.