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

Ge, Jirong; Xie, Liang; Chen, Juan; Li, Shengqiang; Xu, Huijuan; Lai, Yisheng; Qiu, Long-Long; Ni, Chen-Bo

doi:10.1007/s11655-016-2744-2

Cited by 33 publications

(29 citation statements)

References 33 publications

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“…In support of the latter hypothesis, CLCF1 was shown to have modest inhibitory effects on osterix expression and mineralization in primary calvarial osteoblast cultures (10). Variations in CLCF1 levels have been recently associated with postmenopausal osteoporosis (11).…”

mentioning

confidence: 77%

Cardiotrophin-like cytokine (CLCF1) modulates mesenchymal stem cell osteoblastic differentiation

Nahlé

Pasquin

Laplante

et al. 2019

Journal of Biological Chemistry

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Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into adipocytes, chondrocytes, or osteocytes. MSCs secrete an array of cytokines and express the LIFR␤ (leukemia inhibitory factor receptor) chain on their surface. Mutations in the gene coding for LIFR␤ lead to a syndrome with altered bone metabolism. LIFR␤ is one of the signaling receptor chains for cardiotrophin-like cytokine (CLCF1), a neurotrophic factor known to modulate B and myeloid cell functions. We investigated its effect on MSCs induced to differentiate into osteocytes in vitro. Our results indicate that CLCF1 binds mouse MSCs, triggers STAT1 and-3 phosphorylation, inhibits the upregulation of master genes involved in the control of osteogenesis, and markedly prevents osteoblast generation and mineralization. This suggests that CLCF1 could be a target for therapeutic intervention with agents such as cytokine traps or blocking mAbs in bone diseases such as osteoporosis.

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mentioning

confidence: 77%

Cardiotrophin-like cytokine (CLCF1) modulates mesenchymal stem cell osteoblastic differentiation

Nahlé

Pasquin

Laplante

et al. 2019

Journal of Biological Chemistry

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“…The JAK/STAT signaling pathway plays a vital role in bone metabolism. LWDHP regulates immune function by increasing the expression of the immune-related gene cardiotrophin-like cytokine factor 1 and activation of the JAK/STAT signaling pathway to treat postmenopausal osteoporosis with kidney yin deficiency [ 130 ]. Xia et al suggested that LWDHP could alleviate osteoporosis partially via a significant enhancement in the levels of Lrp-5, β -catenin, Runx2, and Osx, which were involved in the canonical Wnt/ β -catenin signaling pathway of osteoblasts, in osteoporosis model induced by ovariectomy and in vitro experiments [ 131 ].…”

Section: Immunoregulation Mechanisms Of Chinese Medicinal Plants Imentioning

confidence: 99%

Prevention and Treatment of Osteoporosis Using Chinese Medicinal Plants: Special Emphasis on Mechanisms of Immune Modulation

Zhao

Zheng

et al. 2018

Journal of Immunology Research

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Numerous studies have examined the pathogenesis of osteoporosis. The causes of osteoporosis include endocrine factors, nutritional status, genetic factors, physical factors, and immune factors. Recent osteoimmunology studies demonstrated that the immune system and immune factors play important regulatory roles in the occurrence of osteoporosis, and people should pay more attention to the relationship between immunity and osteoporosis. Immune and bone cells are located in the bone marrow and share numerous regulatory molecules, signaling molecules, and transcription factors. Abnormal activation of the immune system alters the balance between osteoblasts and osteoclasts, which results in an imbalance of bone remodeling and osteoporosis. The incidence of osteoporosis is also increasing with the aging of China's population, and traditional Chinese medicine has played a vital role in the prevention and treatment of osteoporosis for centuries. Chinese medicinal plants possess unique advantages in the regulation of the immune system and the relationships between osteoporosis and the immune system. In this review, we provide a general overview of Chinese medicinal plants in the prevention and treatment of osteoporosis, focusing on immunological aspects.

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“…Therefore, understanding the time and dose effects of ZGP on BMSC osteogenic differentiation will be clinically relevant in the treatment of OP. Although the effect of classic kidney-tonifying compounds on BMSC osteogenic differentiation is still poorly understood, a few preparations such as six-ingredient rehmannia pill, sexoton pill [ 71 , 72 ], Erxian decoction [ 73 ], and Qing'e pill [ 74 ] have been shown to promote osteogenic differentiation and inhibit angiogenic differentiation of BMSCs. Therefore, it is important to compare the effects of the different kidney-tonifying compounds on BMSC osteogenic differentiation vis-à-vis OP treatment.…”

Section: Future Directions?mentioning

confidence: 99%

Mechanisms of Zuogui Pill in Treating Osteoporosis: Perspective from Bone Marrow Mesenchymal Stem Cells

Yang

You

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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The current treatment strategies for osteoporosis (OP) involve promoting osteogenic differentiation and inhibiting adipogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). According to a theory of traditional Chinese medicine (TCM), the kidneys contain an “essence” that regulate bone metabolism and generate marrow. Kidney disorders are therefore considered to be a major cause of OP as per the principles of TCM, which recommends kidney-tonifying treatments for OP. The Zuogui pill (ZGP) is a classic kidney-tonifying medication that effectively improves OP symptoms. Studies have shown that ZGP can promote the osteogenic differentiation of BMSCs, providing scientific evidence for the TCM theory linking kidneys with bone metabolism. In this review, we have provided an overview of recent studies that examined the underlying mechanisms of ZGP mediated regulation of BMSC osteogenic and adipogenic differentiation.

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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

Abstract: 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.

Cited by 33 publications

References 33 publications

Cardiotrophin-like cytokine (CLCF1) modulates mesenchymal stem cell osteoblastic differentiation

Cardiotrophin-like cytokine (CLCF1) modulates mesenchymal stem cell osteoblastic differentiation

Prevention and Treatment of Osteoporosis Using Chinese Medicinal Plants: Special Emphasis on Mechanisms of Immune Modulation

Mechanisms of Zuogui Pill in Treating Osteoporosis: Perspective from Bone Marrow Mesenchymal Stem Cells

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