Bushenhuoxue formula attenuates cartilage degeneration in an osteoarthritic mouse model through TGF-β/MMP13 signaling.
Bushenhuoxue formula attenuates cartilage degeneration in an osteoarthritic mouse model through TGF-β/MMP13 signaling.
复制标题
补肾活血方通过 TGF-β/MMP13 信号传导减轻骨关节炎小鼠模型中的软骨退化
DOI：
10.1186/s12967-018-1437-3
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发表时间：
2018-03-20
影响因子：
7.4
通讯作者：
Jin H
中科院分区：
文献类型：
--
作者：
Wang PE;Zhang L;Ying J;Jin X;Luo C;Xu S;Dong R;Xiao L;Tong P;Jin H
关节软骨退变在骨关节炎（OA）的发病机制中起着关键作用。补肾活血方（BSHXF）已广泛应用于临床治疗OA。然而，BSHXF的软骨保护作用的分子机制仍有待阐明。本研究的目的是探讨BSHXF对OA小鼠模型的影响。在这项研究中，我们研究了BSHXF对OA小鼠模型中内侧半月板（DMM）诱导的软骨细胞降解不稳定的影响。术后12周，采集关节进行组织分析，包括组织学、组织形态学、TUNEL、OARSI评分、micro-CT和COL2、TGFBR2、pSMAD2和MMP13的免疫组织化学检测。此外，我们还分别通过real-time PCR和Western blot检测了BSHXF对软骨细胞ATDC5中Mmp13 mRNA和蛋白表达的影响。此外，我们还研究了BSHXF对Tgfbr2条件敲除小鼠（Tgfbr2Col2ER小鼠）软骨细胞的软骨保护作用，包括上述相关实验。我们在ATDC5中转染Tgfbr2 siRNA，进一步评估BSHXF处理后Mmp13 mRNA和蛋白表达的变化。术后12周，dmm诱导小鼠软骨降解和软骨细胞凋亡得到改善，软骨面积和厚度、蛋白聚糖基质、COL2含量增加，OARSI评分降低。此外，经BSHXF处理的dmm诱导小鼠TGFBR2和pSMAD2升高，MMP13阳性细胞减少。此外，在含BSHXF的血清中，培养成软骨ATDC5细胞的Mmp13 mRNA和蛋白表达降低。正如预期的那样，Tgfbr2Col2ER小鼠表现出明显的oa样表型。有趣的是，BSHXF处理后，Tgfbr2Col2ER小鼠的关节软骨结构仍有明显改善，通过上调关节软骨中pSMAD2的表达水平，下调关节软骨中MMP13的表达水平。BSHXF可通过TGF-β/MMP13信号通路抑制软骨降解，是治疗骨性关节炎的良好选择。
Articular cartilage degeneration plays a key role in the pathogenesis of osteoarthritis (OA). Bushenhuoxue formula (BSHXF) has been widely used in the treatment of OA in clinics. However, the molecular mechanisms responsible for the chondroprotective effect of BSHXF remain to be elucidated. The purpose of this study was to explore the effects of BSHXF on OA mice model. In this study, we investigated the effects of BSHXF on destabilization of the medial meniscus (DMM)-induced chondrocyte degradation in OA mice model. At 12 weeks post-surgery, the joints were harvested for tissue analyses, including histology, histomorphometry, TUNEL, OARSI scoring, micro-CT and immunohistochemistry for COL2, TGFBR2, pSMAD2 and MMP13. Additionally, we also evaluated the effects of BSHXF on Mmp13 mRNA and protein expression in chondrogenic ATDC5 cells through real-time PCR and Western blot respectively. Moreover, we investigated the chondroprotective effect of BSHXF on mice with Tgfbr2 conditional knockout (Tgfbr2Col2ER mice) in chondrocyte, including the relative experiments mentioned above. We transfected Tgfbr2 siRNA in ATDC5 to further evaluate the changes of Mmp13 mRNA and protein expression followed by BSHXF treatment. Amelioration of cartilage degradation and chondrocyte apoptosis were observed in DMM-induced mice, with increases in cartilage area and thickness, proteoglycan matrix, COL2 content and decreases in OARSI score at 12 weeks post surgery. Moreover, the elevated TGFBR2 and pSMAD2, and reduced MMP13 positive cells were also revealed in DMM-induced mice treated with BSHXF. Besides, decreased Mmp13 mRNA and protein expression were observed inchondrogenic ATDC5 cells culture in serum containing BSHXF. As expected, Tgfbr2Col2ER mice exhibited significant OA-like phenotype. Interestingly, obvious improvement in articular cartilage structure was still observed in Tgfbr2Col2ER mice after BSHXF treatment via up-regulated pSMAD2 and down-regulated MMP13 expressional levels in articular cartilage. BSHXF could inhibit cartilage degradation through TGF-β/MMP13 signaling, and be considered a good option for the treatment of OA.
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影响因子：
--
作者：
Aigner, T;Vornehm, SI;Bayliss, MT
通讯作者：
Bayliss, MT
影响因子：
--
作者：
Shen, Jie;Li, Jia;Wang, Baoli;Jin, Hongting;Wang, Meina;Zhang, Yejia;Yang, Yunzhi;Im, Hee-Jeong;O'Keefe, Regis;Chen, Di
通讯作者：
Chen, Di
DOI：
10.1155/2017/5190986
发表时间：
2017
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Li L;Liu H;Shi W;Liu H;Yang J;Xu D;Huang H;Wu L
通讯作者：
Wu L
影响因子：
--
作者：
Chen, Carol G.;Thuillier, Daniel;Chin, Emily N.;Alliston, Tamara
通讯作者：
Alliston, Tamara
影响因子：
6.2
作者：
Hildebrand, T;Laib, A;Rüegsegger, P
通讯作者：
Rüegsegger, P