Fractions of Shen-Sui-Tong-Zhi Formula Enhance Osteogenesis Via Activation of β-Catenin Signaling in Growth Plate Chondrocytes.
Fractions of Shen-Sui-Tong-Zhi Formula Enhance Osteogenesis Via Activation of β-Catenin Signaling in Growth Plate Chondrocytes.
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DOI：
10.3389/fphar.2021.711004
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发表时间：
2021
影响因子：
5.6
通讯作者：
Jin H
中科院分区：
文献类型：
--
作者：
Xu R;Zeng Q;Xia C;Chen J;Wang P;Zhao S;Yuan W;Lou Z;Lin H;Xia H;Lv S;Xu T;Tong P;Gu M;Jin H
背景：肾髓通脂方治疗骨质疏松症已有数十年的历史，临床疗效显著。本文旨在通过小鼠模型研究，探讨其抗小鼠前列腺增生的最佳有效成分及其确切作用机制。 研究方法：本研究首先筛选了SSTZF提取物体内抗骨质疏松的最佳部位，并进一步探讨了其体内外抗骨质疏松的作用机制。向10周龄雌性C57 BL/6 J小鼠施用SSTZF的每个级分。卵巢切除术（OVX）后10周，收集股骨进行组织分析，包括组织学、显微CT、生物力学测试和ALP、FABP 4和β-连环蛋白的免疫组织化学。此外，我们还检测了SSTZF提取物处理C3 H10 T1/2细胞后ALP和FABP 4 mRNA表达水平以及β-catenin蛋白表达水平。此外，我们通过μCT、组织学和免疫组织化学分析研究了SSTZF提取物对生长板软骨细胞中β-catenin条件性敲除小鼠（β-catenin Gli 1 ER小鼠）的抗骨质疏松作用。 结果如下：治疗10周后，SSTZF正丁醇提取物（SSTZF-NB）组小鼠骨小梁面积和ALP含量增加，脂滴面积和FABP 4含量降低，骨小梁样表型明显改善。用其他提取物处理后没有观察到这种改善，表明SSTZF-NB是最佳的抗骨质疏松级分。此外，在施用SSTZF-NB的OVX小鼠和C3 H10 T1/2细胞中均显示升高的β-连环蛋白。此外，如预期的那样，在β-连环蛋白Gli 1 ER小鼠中观察到显著的类神经纤维变性表型。然而，SSTZF-NB未能挽救β-catenin Gli 1 ER小鼠的恶化，在用SSTZF-NB处理后没有观察到显著的ALP再上调和FABP 4下调，表明SSTZF-NB主要通过β-catenin信号传导防止骨丢失。 结论：SSTZF-NB主要通过激活生长板软骨细胞β-catenin信号通路促进成骨。SSTZF-NB是SSTZF的最佳抗骨质疏松组分，可以被认为是骨质疏松症的有益替代治疗选择。
Background: Shen-sui-tong-zhi formula (SSTZF) has been used to treat osteoporosis for decades and shows excellent clinical efficacy. This article aims to explore the optimal anti-osteoporotic ingredient and its precise mechanisms in mice models. Methods: In this study, we first screened the optimal anti-osteoporosis fraction of SSTZF extract in vivo, and then further explored the mechanism of its effects both in vivo and in vitro. Ten-week-old female C57BL/6J mice were administrated with each fraction of SSTZF. At 10 weeks after ovariectomy (OVX), femurs were collected for tissue analyses, including histology, micro-CT, biomechanical tests, and immunohistochemistry for ALP, FABP4, and β-catenin. Additionally, we also evaluated the mRNA expression level of ALP and FABP4 and the protein expression level of β-catenin after being treated with SSTZF extract in C3H10T1/2 cells. Moreover, we investigated the anti-osteoporosis effect of SSTZF extract on mice with β-catenin conditional knockout in growth plate chondrocytes (β-catenin Gli1ER mice) through μCT, histology, and immunohistochemistry analyzes. Results: At 10 weeks after treatment, osteoporosis-like phenotype were significantly ameliorated in SSTZF n-butanol extract (SSTZF-NB) group mice, as indicated by increased trabecular bone area and ALP content, and decreased lipid droplet area and FABP4 content. No such improvements were observed after being treated with other extracts, demonstrating that SSTZF-NB is the optimal anti-osteoporosis fraction. Additionally, the elevated β-catenin was revealed in both OVX mice and C3H10T1/2 cells with SSTZF-NB administered. Furthermore, a significant osteoporosis-like phenotype was observed in β-catenin Gli1ER mice as expected. However, SSTZF-NB failed to rescue the deterioration in β-catenin Gli1ER mice, no significant re-upregulated ALP and downregulated FABP4 were observed after being treated with SSTZF-NB, demonstrating that SSTZF-NB prevents bone loss mainly via β-catenin signaling. Conclusion: SSTZF-NB enhances osteogenesis mainly via activation of β-catenin signaling in growth plate chondrocytes. SSTZF-NB is the optimal anti-osteoporosis fraction of SSTZF and it can be considered a salutary alternative therapeutic option for osteoporosis.
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影响因子：
12.4
作者：
Chen Q;Shou P;Zheng C;Jiang M;Cao G;Yang Q;Cao J;Xie N;Velletri T;Zhang X;Xu C;Zhang L;Yang H;Hou J;Wang Y;Shi Y
通讯作者：
Shi Y
间充质干细胞：成骨细胞或脂肪细胞的细胞命运决定及其在骨质疏松症治疗中的应用
影响因子：
5.6
作者：
Hu L;Yin C;Zhao F;Ali A;Ma J;Qian A
通讯作者：
Qian A
影响因子：
6.7
作者：
Jung, Hyun Ah;Ali, Md. Yousof;Choi, Jae Sue
通讯作者：
Choi, Jae Sue
影响因子：
4.2
作者：
Kim, HJ;Bae, YC;Lee, WJ
通讯作者：
Lee, WJ
DOI：
10.1007/bf02857813
发表时间：
1991-01-01
期刊：
Archives of Pharmacal Research (Seoul)
影响因子：
--
作者：
CHOI J S;SUH S S;PARK H J
通讯作者：
PARK H J