Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, PR China.
Int J Biol Sci. 2021 Apr 24;17(7):1821-1836. doi: 10.7150/ijbs.57681. eCollection 2021.
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 , 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-3β/β-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-3β/β-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-3β/β-catenin signaling may be a promising therapeutic target for patients during DO treatment.
成骨细胞和破骨前体细胞都有助于成骨和血管生成的偶联，从而调节骨再生。黄芪甲苷（AS-IV）是一种来源于中药的环阿尔廷型三萜糖苷，具有多种生物学活性，包括刺激血管生成和减轻缺血缺氧损伤。然而，AS-IV 在成骨、破骨细胞生成和骨再生中的作用及其潜在机制仍知之甚少。在本研究中，我们发现 AS-IV 处理抑制破骨细胞生成，保留破骨前体细胞，并增强血小板衍生生长因子-BB（PDGF-BB）诱导的血管生成。此外，AS-IV 促进骨髓间充质干细胞（BMSCs）的细胞活力、成骨分化和血管生成基因表达。发现 AKT/GSK-3β/β-catenin 信号的激活有助于 AS-IV 对破骨细胞生成和成骨的作用。此外，AS-IV 加速了牵引成骨（DO）期间的骨再生，从影像学和组织学表现以及生物力学参数的改善得到证明，伴随着牵引区血管生成的增强。总之，AS-IV 通过同时增强成骨和破骨前体细胞诱导的血管生成来加速 DO 期间的骨再生，部分通过 AKT/GSK-3β/β-catenin 信号。这些发现表明 AS-IV 可能是一种促进成骨和血管生成偶联的潜在生物活性分子，并暗示 AKT/GSK-3β/β-catenin 信号可能是 DO 治疗期间患者的有希望的治疗靶点。
