期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 17, 期 7, 页码 1821-1836出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.57681
关键词
astragaloside IV; preosteoclast; angiogenesis; bone marrow mesenchymal stem cell; distraction osteogenesis
资金
- National Natural Science Foundation of China [82072421, 81930069]
- National natural science foundation of China youth program [81802156]
- Major scientific research and innovation project of Shanghai municipal education commission [2019-01-07-00-02-E00043]
Astragaloside IV (AS-IV) accelerates bone regeneration during distraction osteogenesis by enhancing osteogenesis and preosteoclast-induced angiogenesis simultaneously, partially through AKT/GSK-3 beta/beta-catenin signaling. These findings suggest that AS-IV may serve as a potential bioactive molecule for promoting the coupling of osteogenesis and angiogenesis, and imply that AKT/GSK-3 beta/beta-catenin signaling may be a promising therapeutic target for patients during distraction osteogenesis treatment.
Both osteoblasts and preosteoclasts contribute to the coupling of osteogenesis and angiogenesis, regulating bone regeneration. Astragaloside IV (AS-IV), a glycoside of cycloartane-type triterpene derived from the Chinese herb Astragalus membranaceus, exhibits various biological activities, including stimulating angiogenesis and attenuating ischemic-hypoxic injury. However, the effects and underlying mechanisms of AS-IV in osteogenesis, osteoclastogenesis, and bone regeneration remain poorly understood. In the present study, we found that AS-IV treatment inhibited osteoclastogenesis, preserved preosteoclasts, and enhanced platelet-derived growth factor-BB (PDGF-BB)-induced angiogenesis. Additionally, AS-IV promoted cell viability, osteogenic differentiation, and angiogenic gene expression in bone marrow mesenchymal stem cells (BMSCs). The activation of AKT/GSK-3 beta/beta-catenin signaling was found to contribute to the effects of AS-IV on osteoclastogenesis and osteogenesis. Furthermore, AS-IV accelerated bone regeneration during distraction osteogenesis (DO), as evidenced from the improved radiological and histological manifestations and biomechanical parameters, accompanied by enhanced angiogenesis within the distraction zone. In summary, AS-IV accelerates bone regeneration during DO, by enhancing osteogenesis and preosteoclast-induced angiogenesis simultaneously, partially through AKT/GSK-3 beta/beta-catenin signaling. These findings reveal that AS-IV may serve as a potential bioactive molecule for promoting the coupling of osteogenesis and angiogenesis, and imply that AKT/GSK-3 beta/beta-catenin signaling may be a promising therapeutic target for patients during DO treatment.
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