Bushenhuoxue Formula Facilitates Articular Cartilage Repair and Attenuates Matrix Degradation by Activation of TGF-β Signaling Pathway.
Bushenhuoxue Formula Facilitates Articular Cartilage Repair and Attenuates Matrix Degradation by Activation of TGF-β Signaling Pathway.
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补肾活血方通过激活 TGF-β 信号通路促进关节软骨修复并减轻基质降解。
DOI：
10.1155/2018/2734581
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Wang P
中科院分区：
文献类型：
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作者：
Dong R;Ying J;Xu T;Hu S;Zhang P;Xia C;Fang L;Jin H;Wang P
探讨补肾活血方对关节软骨修复的影响及其机制。将24只全层软骨缺损大鼠分为模型组和BSHX组（给予BSHX方治疗）。治疗4周、8周后分别进行宏观观察和组织病理学观察。此外，我们还评估了在BSHX配方介导的血清中培养的软骨ATDC5细胞中的软骨细胞增殖、细胞外基质（ECM）沉积、软骨降解和软骨细胞肥大相关基因表达。此外，我们在TGF βr2 siRNA转染的软骨ATDC5细胞中检测了上述基因的表达和pSMAD2/3蛋白水平，以确定BSHX配方是否通过TGF-β信号通路发挥软骨修复作用。BSHX方对软骨缺损大鼠软骨再生有促进作用，Col2、pSMAD2升高，Mmp13、Runx2降低。此外，在BSHX方介导的血清中培养的软骨性ATDC5细胞中也观察到细胞增殖，Col2a1、Aggrecan和pSMAD2/3升高，Mmp13、Adamts5、Col10a1和Runx2表达降低。此外，在Tgfβr2下调的软骨性ATDC5细胞中，ECM沉积、软骨降解、软骨细胞肥大相关基因及pSMAD2/3蛋白表达水平的改变不能通过BSHX方处理来调节。BSHX方通过激活TGF-β信号，通过加速软骨细胞增殖和维持软骨细胞表型，促进关节软骨修复，上调ECM积累，抑制基质降解。
To investigate the effect and underlying mechanism of Bushenhuoxue (BSHX) formula on articular cartilage repair. Twenty-four full-thickness cartilage defect rats were divided into two groups: model group and BSHX group (treated with BSHX formula). Macroscopic observation and histopathological study were conducted after 4- and 8-week treatment. Additionally, we also evaluated chondrocyte proliferation, extracellular matrix (ECM) deposition, cartilage degradation, and chondrocyte hypertrophy-related genes expression in chondrogenic ATDC5 cells cultured in BSHX formula-mediated serum. Moreover, we assessed aforementioned genes expression and pSMAD2/3 protein level in Tgfβr2 siRNA transfected chondrogenic ATDC5 cells in order to address whether BSHX formula exerts cartilage repairing effect through TGF-β signaling. Neocartilage regeneration promotion effect was observed in cartilage defect rats after BSHX formula treatment, with increases in Col2 and pSMAD2 and decreases in Mmp13 and Runx2. Moreover, cell proliferation, the elevated Col2a1, Aggrecan and pSMAD2/3, reduced Mmp13, Adamts5, Col10a1, and Runx2 expression were also observed in chondrogenic ATDC5 cells cultured in BSHX formula-mediated serum. Besides, the expression alteration of ECM deposition, cartilage degradation, chondrocyte hypertrophy-related genes, and pSMAD2/3 protein levels presented in Tgfβr2 downregulated chondrogenic ATDC5 cells couldn't be adjusted by BSHX formula treatment. By activation of TGF-β signaling, BSHX formula can promote articular cartilage repair by accelerating chondrocyte proliferation and maintaining chondrocyte phenotype, upregulate ECM accumulation, and inhibit matrix degradation.