Bushen Zhuangjin Decoction promotes chondrocyte proliferation by stimulating cell cycle progression

Li, Xihai; Chen, Jiashou; Liang, Wenna; Li, Huiting; Liu, Fayuan; Weng, Xiaping; Lin, Pingdong; Chen, Wenlie; Zheng, Chengchao; Xu, Huifeng; Liu, Xianxiang; Ye, Hongzhi

doi:10.3892/etm.2015.2214

Cited by 14 publications

(15 citation statements)

References 21 publications

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“…It regulates chondrogenes at different stages in different ways, and plays a crucial role in the physiopathology of OA ( 22 – 24 ). Altering the expression of genes and proteins in articular chondrocytes is correlated with the pathological process of OA ( 25 ). Several molecular components of the Wnt/β-catenin signaling pathway have been shown to be associated with OA, including Wnt-4, Frizzled-2, β-catenin and GSK-3β.…”

Section: Discussionmentioning

confidence: 99%

Psoralen promotes the expression of cyclin D1 in chondrocytes via the Wnt/β-catenin signaling pathway

Zheng

Lin

et al. 2017

International Journal of Molecular Medicine

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Psoralen (PSO), the active ingredient of Fructus Psoraleae (FP) the dried ripe fruit of Psoralea corylifolia L., has been commonly used in traditional Chinese medicine (TCM) for the treatment of osteoarthritis (OA). We found that PSO activates cartilaginous cellular functions of rat chondrocytes in vitro. However, the effect of PSO on chondrocyte proliferation and the precise mechanisms involved remain to be elucidated. We investigated the effects of PSO on chondrocytes isolated from Sprague-Dawley (SD) rats and evaluated involvement of the Wnt/β-catenin signaling pathway. The viability of chondrocytes treated with PSO was increased in a dose- and time-dependent manner, as assessed by MTT assay. We found that the gene expression and protein levels of Wnt-4, Frizzled-2, β-catenin and cyclin D1 in the PSO-treated chondrocytes were significantly upregulated, while the gene expression and protein level of glycogen synthase kinase-3β (GSK-3β) were downregulated, compared with the untreated chondrocytes. By immunofluorescence, we also found that PSO induced β-catenin nuclear translocation. Importantly, the expression of β-catenin and cyclin D1 was partly inhibited by Dickkopf-1 (DKK-1), an inhibitor of the Wnt/β-catenin signaling pathway. Additionally, Col-II expression in chondrocytes was increased after treatment with PSO. Taken together, these results indicate that PSO promotes chondrocyte proliferation by activating the Wnt/β-catenin signaling pathway, and it may play an important role in the treatment of OA.

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Section: Discussionmentioning

confidence: 99%

Psoralen promotes the expression of cyclin D1 in chondrocytes via the Wnt/β-catenin signaling pathway

Zheng

Lin

et al. 2017

International Journal of Molecular Medicine

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“…Moreover, it exerts potentially drug-like and multi-target effects ( 37 , 38 ). There is evidence that BZD is effective in the treatment of OA in both clinical and in in vitro studies ( 16 , 17 ).…”

Section: Discussionmentioning

confidence: 99%

“…Bushen Zhuangjin decoction (BZD) is a well-known formulation that nourishes the Gan (liver) and the Shen (kidney) and also strengthens tendons and bones, and has been long used in China ( 16 ). Clinical studies have demonstrated that BZD has a positive effect on the treatment of OA, and experimental studies have found that BZD decreases the apoptosis of chondrocytes and promotes chondrocyte proliferation ( 17 , 18 ). However, the specific mechanisms responsible for the inhibitory effects of BZD on ER stress-mediated chondrocyte apoptosis remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Bushen Zhuangjin decoction inhibits TM-induced chondrocyte apoptosis mediated by endoplasmic reticulum stress

Lin

Weng

Liu

et al. 2015

International Journal of Molecular Medicine

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Chondrocyte apoptosis triggered by endoplasmic reticulum (ER) stress plays a vital role in the pathogenesis of osteoarthritis (OA). Bushen Zhuangjin decoction (BZD) has been widely used in the treatment of OA. However, the cellular and molecular mechanisms responsible for the inhibitory effects of BZD on chondrocyte apoptosis remain to be elucidated. In the present study, we investigated the effects of BZD on ER stress-induced chondrocyte apoptosis using a chondrocyte in vitro model of OA. Chondrocytes obtained from the articular cartilage of the knee joints of Sprague Dawley (SD) rats were detected by immunohistochemical staining for type II collagen. The ER stress-mediated apoptosis of tunicamycin (TM)-stimulated chondrocytes was detected using 4-phenylbutyric acid (4-PBA). We found that 4-PBA inhibited TM-induced chondrocyte apoptosis, which confirmed the successful induction of chondrocyte apoptosis. BZD enhanced the viability of the TM-stimulated chondrocytes in a dose- and time-dependent manner, as shown by MTT assay. The apoptotic rate and the loss of mitochondrial membrane potential (ΔΨm) of the TM-stimulated chondrocytes treated with BZD was markedly decreased compared with those of chondrocytes not treated with BZD, as shown by 4′,6-diamidino-2-phenylindole (DAPI) staining, Annexin V-FITC binding assay and JC-1 assay. To further elucidate the mechanisms responsible for the inhibitory effects of BZD on TM-induced chondrocyte apoptosis mediated by ER stress, the mRNA and protein expression levels of binding immunoglobulin protein (Bip), X-box binding protein 1 (Xbp1), activating transcription factor 4 (Atf4), C/EBP-homologous protein (Chop), caspase-9, caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were measured by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. In the TM-stimulated chondrocytes treated with BZD, the mRNA and protein expression levels of Bip, Atf4, Chop, caspase-9, caspase-3 and Bax were significantly decreased, whereas the mRNA and protein expression levels of Xbp1 and Bcl-2 were significantly increased compared with the TM-stimulated chondrocytes not treated with BZD. Additionally, all our findings demonstrated that there was no significant difference between the TM-stimulated chondrocytes treated with BZD and those treated with 4-PBA. Taken together, our results indicate that BZD inhibits TM-induced chondrocyte apoptosis mediated by ER stress. Thus, BZD may be a potential therapeutic agent for use in the treatment of OA.

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“…Achyranthes bidentata polysaccharides are found in chondrocytes in vitro to induce G1/S cell cycle transition and type II collagen expression by upregulating the expression of CDK4, CDK6, and Cyclin D1, which are related to the Wnt/ β -catenin signaling pathway [ 94 ]. Bushen Zhuangjin Decoction [ 95 ] and Duhuo Jisheng Decoction [ 96 ] are also found to increase the expression of CDK4, CDK6, and Cyclin D1 and accelerate G1/S cell cycle transition, whereas they decrease the expression of p21. Bauhinia championi (Benth.)…”

Section: Proliferative Activity Of Tcmmentioning

confidence: 99%

Insights into the Action Mechanisms of Traditional Chinese Medicine in Osteoarthritis

Liu

Shi

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Osteoarthritis (OA) is a chronic degenerative joint disease characterized by articular cartilage destruction, synovial inflammation, and osteophyte formation. No effective treatments are available. The current pharmacological medications such as nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics, accompanied by possible adverse effects, might ameliorate OA symptoms. But they do not arrest the progression of OA. Traditional Chinese medicine (TCM) provides medical value by modification of disease and symptoms in OA. Valuable work on exploring TCM merits for OA patients has been investigated using modern technologies, although the complicated interacting network among the numerous components indicates the uncertainty of target specification. This review will provide an overview of the action mechanism of TCM in the last 5 years, discussing the TCM activities of anti-inflammation, antiapoptosis, antioxidation, anticatabolism, and proliferation in OA. TCM is a proposed medical option for OA treatment.

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Bushen Zhuangjin Decoction promotes chondrocyte proliferation by stimulating cell cycle progression

Cited by 14 publications

References 21 publications

Psoralen promotes the expression of cyclin D1 in chondrocytes via the Wnt/β-catenin signaling pathway

Psoralen promotes the expression of cyclin D1 in chondrocytes via the Wnt/β-catenin signaling pathway

Bushen Zhuangjin decoction inhibits TM-induced chondrocyte apoptosis mediated by endoplasmic reticulum stress

Insights into the Action Mechanisms of Traditional Chinese Medicine in Osteoarthritis

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