Chen Fangping, Liang Qing, Mao Lijie, Yin Yanrong, Zhang Lixin, Li Cuidi, Liu Changsheng
Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai, 200237, PR China.
Engineering Research Center for Biomedical Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, PR China.
Bioact Mater. 2021 Sep 10;10:335-344. doi: 10.1016/j.bioactmat.2021.09.001. eCollection 2022 Apr.
Osteoporosis is a reduction in skeletal mass due to the decrease of osteogenic ability and the activation of the osteoclastic function. Inhibiting bone resorption and accelerating the new bone formation is a promising strategy to repair the bone defect of osteoporosis. In this study, we first systematically investigated the roles of Chinese medicine Asperosaponin VI (ASP VI) on osteogenic mineralization of BMSCs and osteoclastogenesis of BMMs, and then explored the synergistic effect of ASP VI and BS (BMP-2 immobilized in 2-N, 6-O-sulfated chitosan) on bone formation. The result showed that ASP VI with the concentration lower than 10 M contributed to the expression of osteogenic gene and inhibited osteoclastic genes RANKL of BMSCs. Simultaneously, ASP VI significantly reduced the differentiation of mononuclear osteoclasts in the process of osteoclast formation induced by M-CSF and RANKL. Furthermore, by stimulating the SMADs, TGF-β1, VEGFA, and OPG/RANKL signaling pathways, ASBS (ASP VI and BS) substantially enhanced osteogenesis, greatly promoted angiogenesis, and suppressed osteoclastogenesis. The findings provide a new perspective on osteoporosis care and prevention.
骨质疏松症是由于成骨能力下降和破骨细胞功能激活导致的骨量减少。抑制骨吸收并加速新骨形成是修复骨质疏松症骨缺损的一种有前景的策略。在本研究中，我们首先系统地研究了中药天冬皂苷 VI（ASP VI）对骨髓间充质干细胞（BMSCs）成骨矿化和骨髓巨噬细胞（BMMs）破骨细胞生成的作用，然后探讨了 ASP VI 与 BS（固定在 2-N，6-O-硫酸化壳聚糖上的骨形态发生蛋白-2）对骨形成的协同作用。结果表明，浓度低于 10 μM 的 ASP VI 有助于成骨基因的表达，并抑制 BMSCs 的破骨细胞基因 RANKL。同时，ASP VI 在 M-CSF 和 RANKL 诱导的破骨细胞形成过程中显著降低单核破骨细胞的分化。此外，通过刺激 SMADs、TGF-β1、VEGFA 和 OPG/RANKL 信号通路，ASBS（ASP VI 和 BS）显著增强成骨作用，极大地促进血管生成，并抑制破骨细胞生成。这些发现为骨质疏松症的护理和预防提供了新的视角。
