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Liuwei Dihuang Pill (六味地黄丸) Treats Postmenopausal Osteoporosis with Shen (Kidney) Yin Deficiency via Janus Kinase/Signal Transducer and Activator of Transcription Signal Pathway by Up-regulating Cardiotrophin-Like Cytokine Factor 1 Expression
  
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KeyWord:postmenopausal osteoporosis, Chinese medicine, Shen (Kidney) yin deficiency, cardiotrophin-like cytokine factor 1 gene, Liuwei Dihuang Pill, Janus kinase/signal transducer and activator of transcription signaling pathway
Author NameAffiliationE-mail
GE Ji-rong Key Research Laboratory of Osteoporosis Syndrome Genomics, Fujian Academy of Traditional Chinese Medicine, Fuzhou (350003), China jironggecn@163.com 
XIE Li-hua, CHEN Juan, LI Sheng-qiang   
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Abstract:
      Objectives: To investigate the mechanism of Liuwei Dihuang Pill (六味地黄丸, LDP) in treating postmenopausal osteoporosis (PMOP) with Shen (Kidney) yin deficiency. Methods: In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group (Group A), PMOP Shen-yang deficiency group (Group B), PMOP without Shen deficiency group (Group C), and control group (Group N). Real-time polymerase chain reaction (RT-PCR) and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 (CLCF1), ankyrin repeat and SOCS box containing 1 (ASB1), and prokineticin 2 (PROK2) genes and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Results: The mRNA (P<0.05) and protein (P<0.01) expression levels of the CLCF1 gene in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gene were obviously up-regulated (P<0.01). After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated (both P<0.01), and the average bone density of the top femur had significantly increased (P<0.05). In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3. Conclusions: The CLCF1 gene is an important gene associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gene expression and activation of the JAK/STAT signaling pathway.
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