QiangGuYin Modulates the OPG/RANKL/RANK Pathway by Increasing Secretin Levels during Treatment of Primary Type I Osteoporosis

QiangGuYin (QGY) is a common Traditional Chinese medicine prescription for the treatment of osteoporosis. Previous clinical studies have found that QGY effectively improves bone mineral density (BMD) in postmenopausal women, but its underlying mechanism remains unclear. The osteoprotegerin (OPG)/receptor activator of nuclear factor kappa B ligand (RANKL)/receptor activator of nuclear factor kappa B (RANK) pathway is a classic pathway involved in osteoporosis. Secretin levels are a serum marker of osteoporosis, but their effect on the OPG/RANKL/RANK pathway has not been reported. Hence, we investigated the relationship between the OPG/RANKL/RANK pathway and secretin and further revealed the mechanism underlying the effect of QGY in the treatment of osteoporosis. Mice were divided into secretin knockdown, secretin overexpression, and corresponding control groups. Micro-computed tomography was used to detect BMD in different groups, and the results show that QGY significantly improved BMD in mice of the secretin knockdown group. To further verify this, the serum levels of OPG, RANKL, RANK, and secretin were measured by enzyme-linked immunosorbent assays, and femur levels of OPG, RANKL, RANK, and secretin were evaluated by real-time quantitative PCR and western blotting. The results show that the expression of OPG was inhibited and that of RANKL and RANK was increased in mice from the secretin knockdown group, whereas the expression of OPG was upregulated and that of RANKL and RANK was downregulated after QGY intervention. Therefore, QGY inhibited bone resorption by promoting the expression of secretin and modulating the OPG/RANKL/RANK pathway. In addition to the effect of QGY, we also revealed the general regulatory effect of secretin on the OPG/RANKL/RANK pathway. We conclude that QGY modulates the OPG/RANKL/RANK pathway by increasing secretin levels during treatment of primary type I osteoporosis. This work provides a theoretical basis for the clinical use of QGY in the treatment of osteoporosis.

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Vitamin C Activates Osteoblastogenesis and Inhibits Osteoclastogenesis via Wnt/β-Catenin/ATF4 Signaling Pathways

Nutrients ◽

10.3390/nu11030506 ◽

2019 ◽

Vol 11 (3) ◽

pp. 506 ◽

Cited By ~ 7

Author(s):

Hyeon Choi ◽

Gyeong-Ji Kim ◽

Han-Seok Yoo ◽

Da Song ◽

Kang-Hyun Chung ◽

...

Keyword(s):

Transcription Factor ◽

Vitamin C ◽

Signaling Pathways ◽

Nuclear Factor Kappa B ◽

Type I ◽

Nuclear Factor ◽

Mineral Density ◽

Nuclear Factor Kappa ◽

Ovx Rats ◽

Receptor Activator

This study evaluated the effects of vitamin C on osteogenic differentiation and osteoclast formation, and the effects of vitamin C concentration on bone microstructure in ovariectomized (OVX) Wistar rats. Micro-computed tomography analysis revealed the recovery of bone mineral density and bone separation in OVX rats treated with vitamin C. Histomorphometrical analysis revealed improvements in the number of osteoblasts, osteoclasts, and osteocytes; the osteoblast and osteoclast surface per bone surface; and bone volume in vitamin C-treated OVX rats. The vitamin C-treated group additionally displayed an increase in the expression of osteoblast differentiation genes, including bone morphogenetic protein-2, small mothers against decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin, and type I collagen. Vitamin C reduced the expression of osteoclast differentiation genes, such as receptor activator of nuclear factor kappa-B, receptor activator of nuclear factor kappa-B ligand, tartrate-resistant acid phosphatase, and cathepsin K. This study is the first to show that vitamin C can inhibit osteoporosis by promoting osteoblast formation and blocking osteoclastogenesis through the activation of wingless-type MMTV integration site family/β-catenin/activating transcription factor 4 signaling, which is achieved through the serine/threonine kinase and mitogen-activated protein kinase signaling pathways. Therefore, our results suggest that vitamin C improves bone regeneration.

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Influence of copper-zinc sulfide ores elements on bone tissue remodeling and regulative factors

Kazan medical journal ◽

10.17750/kmj2015-783 ◽

2015 ◽

Vol 96 (5) ◽

pp. 783-787 ◽

Cited By ~ 1

Author(s):

E R Farshatova ◽

T I Ganeev ◽

I A Men’shikova ◽

L V Sarmeneeva ◽

N V Nurgaleev ◽

...

Keyword(s):

Parathyroid Hormone ◽

Bone Remodeling ◽

Zinc Sulfide ◽

Nuclear Factor Kappa B ◽

Type I ◽

Nuclear Factor ◽

Nuclear Factor Kappa ◽

Receptor Activator ◽

Sulfide Ore ◽

Copper Zinc

Aim. Characterize the intensity of bone remodeling, balance of hormones and local cytokines regulating bone remodeling and bone metabolism, at chronic intake of copper-zinc sulfide ores elements. Methods. A total of 101 miner, producing copper-zinc sulfide ore by underground mining, and 30 employees of ground services of OAO «Uchaly Mining and Processing Plant», were examined. Experimental studies were performed on 60 white adult male rats, distributed to control and experimental groups. The experimental animals of the study group got copper-zinc sulfide ore powder in a 2% starch solution daily for 3 months as a suspension at the dose of 60 mg per 100 g of body weight. The serum levels of testosterone, parathyroid hormone, total thyroxine and triiodothyronine, cortisol, 25-hydroxyvitamin D, soluble Receptor activator of nuclear factor kappa-B ligand, osteoprotegerin, sclerostin and C-terminal telopeptide of collagen type I, as well as bone alkaline phosphatase activity were determined. Results. Miners who were diagnosed with decreased bone density had increased level of C-terminal telopeptide of collagen type I, with bone alkaline phosphatase activity similar to the control group. In miners with physiological level of bone density, there was no statistically significant decrease in blood testosterone level, in the groups with low and very low bone mineral density there was a statistically significant decrease in testosterone level and increased level of parathyroid hormone. Experimental animals exposed to sulfide ore had serum levels of testosterone, 25-hydroxyvitamin D, thyroxine and triiodothyronine decreased, and increased level of parathyroid hormone and cortisol. Together with that, blood concentration of sclerostin was increased, level of osteoprotegerin - decreased, and soluble Receptor activator of nuclear factor kappa-B ligand was not changed. Conclusion. Long-term intake of copper-zinc sulfide ore leads to an imbalance of bone remodeling with a predominance of resorption. It is associated with the reduction of testosterone, calcidiol and thyroid hormones levels providing anabolic and anti-catabolic effect on bone metabolism, and overproduction of parathyroid hormone and cortisol, stimulating osteolysis. Receptor activator of nuclear factor kappa-B ligand / osteoprotegerin ratio and sclerostin level increases.

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The Mechanisms of Action of Zuogui Pill on Osteoporosis in Ovariectomized Rats

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.20:247-252 ◽

2021 ◽

Vol 20 (2) ◽

pp. 247-252

Author(s):

Ruran Wang ◽

Yanhua Feng ◽

Shengnan Huang ◽

Yujie Zhang ◽

Meijie Liu ◽

...

Keyword(s):

Bone Mineral Density ◽

Bone Mineral ◽

Nuclear Factor Kappa B ◽

Ovariectomized Rats ◽

Nuclear Factor ◽

Mineral Density ◽

Trabecular Thickness ◽

Nuclear Factor Kappa ◽

Receptor Activator ◽

Zuogui Pill

Traditional Chinese medicine recommends kidney-tonifying treatment for osteoporosis. Zuogui pill is one such treatment composed of eight well characterized Chinese medicinal herbs (Radix rehmanniae preparata, Fructus lycii, Rhizoma dioscoreae, F. corni, Semen cuscutae, Colla cornus cervi, C. carapacis et Plastri testudinis, and R. achyranthis bidentatae). The aim of the study is to evaluate the effects of the Zuogui pill on osteoporosis in ovariectomized rats and to identify the signaling pathways that mediate its action on the bones. A total of 46 6-month-old female Sprague-Dawley rats were divided into four groups: sham-operated control, bilaterally ovariectomized, ovariectomized rats receiving diethylstilbestrol (the positive control group), and ovariectomized rats receiving the Zuogui pill. By the end of 8-week treatments, the following parameters were assessed: (a) bone mineral density and trabecular histomorphology, (b) the expression levels of receptor activator of nuclear factor kappa B ligand and osteoprotegerin in rat tibial osteoblasts and (c) bone marrow stromal cells. The Zuogui pill treatment elevated the trabecular bone area and trabecular thickness and reduced the trabecular spacing in rats with ovariectomy-induced osteoporosis. Compared to the ovariectomized group, the Zuogui pill treatment significantly increased the levels of bone mineral density and osteoprotegerin and suppressed the level of receptor activator of the nuclear factor kappa B ligand. These data led us to conclude that the Zuogui pill regulates bone metabolism and improves osteoporosis symptoms possibly through the osteoprotegerin/receptor activator of the nuclear factor kappa B ligand/receptor activator of the nuclear factor kappa B signaling pathway.

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OPG/RANK/RANKL signaling axis in patients with type I diabetes: Associations with parathormone and vitamin D

Italian Journal of Pediatrics ◽

10.1186/s13052-019-0748-1 ◽

2019 ◽

Vol 45 (1) ◽

Cited By ~ 2

Author(s):

Paraskevi Karalazou ◽

Dimitrios Ntelios ◽

Fani Chatzopoulou ◽

Aikaterini Fragou ◽

Maria Taousani ◽

...

Keyword(s):

Vitamin D ◽

Nuclear Factor Kappa B ◽

Bone Structure ◽

Type I Diabetes ◽

Type I ◽

Nuclear Factor ◽

Nuclear Factor Kappa ◽

Receptor Activator ◽

Signaling Axis ◽

Serum Rankl

Abstract Background Type 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism. On the other hand, the important role of the RANKL/OPG/RANK signaling axis in bone physiology is well established. The aim of this study was to evaluate the levels of receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor kappa-B (RANK) and plasma osteoprotegerin (OPG) levels, in T1D youngsters and to investigate factors that could influence the OPG/RANK/RANKL signaling axis such as 25-hydroxy vitamin D [25(OH) D], parathormone (PTH) and age. Methods Serum RANKL, RANK, 25(OH) D, PTH levels and plasma OPG levels, were measured in 71 youngsters with T1D and 50 healthy controls matched for age and gender. Results Plasma OPG levels were significantly lower (p = 0.025) in T1D patients compared to controls. Serum RANKL levels were significantly higher (p = 0.037), while no differences were observed in serum RANK levels (p = 0.946) between the two groups. Serum 25(OH) D levels found significantly decreased (p < 0.001) while serum PTH levels were significantly elevated (p < 0.001) in T1D patients than in controls. Conclusions Our results demonstrated that OPG and RANKL may be promising biomarkers for T1D patients. However, their circulating levels were associated with several factors including PTH, 25(OH) D and therefore, may represent an integrative biomarker for a variety of endocrine signaling disturbances observed in T1D.

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