scholarly journals Water Extract ofDryopteris crassirhizomaAttenuates Bone Loss by Suppressing Osteoclast Differentiation and Function

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hyunil Ha ◽  
Ki-Shuk Shim ◽  
Taesoo Kim ◽  
Hyosun An ◽  
Jin Yeul Ma
Keyword(s):  
Bone Loss ◽  
Protective Effect ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Inhibitory Effect ◽  
Ring Structure ◽  
Nuclear Factor ◽  
Actin Ring ◽  
Activated T Cells ◽  
Osteoclast Precursors

The rhizome ofDryopteris crassirhizomahas been used as a traditional herbal medicine for treating various inflammatory and infectious diseases such as tapeworm infestation and mumps. In the present study, we investigated the bone protective effect of water extract of the rhizome ofDryopteris crassirhizoma(WEDC). We found that WEDC inhibits osteoclast differentiation via directly acting on osteoclast precursors. In osteoclast precursors, WEDC inhibited receptor activator of nuclear factor-κB ligand- (RANKL-) induced expression of c-Fos and nuclear factor of activated T cells cytoplasmic 1, a key downstream target of c-Fos during osteoclast differentiation. We found that WEDC inhibits RNAKL-induced activation of extracellular-regulated kinase and NF-κB that mediates c-Fos expression and osteoclast differentiation. In addition to the inhibitory effect of osteoclast differentiation, WEDC markedly suppressed bon-resorbing activity of mature osteoclasts, which was accompanied by disruption of actin ring structure. Furthermore, administration of WEDC suppressed RANKL-induced trabecular bone loss in mice. Collectively, our results demonstrate that WEDC inhibits not only osteoclast differentiation by inhibiting RANK signaling pathways in osteoclast precursors but also bone resorption by disrupting actin ring in mature osteoclasts, thereby contributing to its protective effect on bone loss.

scholarly journals Forsythia suspensa Protects against Bone Loss in Ovariectomized Mice

Nutrients ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1831 ◽  
Author(s):  
Youn-Hwan Hwang ◽  
Seon-A Jang ◽  
Taesoo Kim ◽  
Hyunil Ha
Keyword(s):  
Bone Loss ◽  
Trabecular Bone ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Nuclear Factor ◽  
Micro Computed Tomography ◽  
Activated T Cells ◽  
Beneficial Effects ◽  
Ovariectomized Mice ◽  
Forsythia Suspensa

In traditional oriental medicine, the fruit of Forsythia suspensa has been used as a nutritional supplement to alleviate inflammation and treat gastrointestinal diseases. However, there is no information available on its beneficial effects on bone. We investigated the beneficial effects of F. suspensa water extract (WFS) on osteoclast differentiation and bone loss. The microarchitecture of trabecular bone was analyzed by micro-computed tomography. Osteoclast differentiation was evaluated based on tartrate-resistant alkaline phosphatase activity, and bone resorption activity was examined on a bone-like mineral surface. The mechanism of action of WFS was assessed by evaluating the expression and activation of signaling molecules. Phytochemical constituents were identified and quantitated by ultrahigh-performance liquid chromatography–tandem mass spectrometry. WFS reduced ovariectomy-induced trabecular bone loss and inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and resorption activity. WFS suppressed RANKL-induced expression of nuclear factor of activated T cells cytoplasmic 1, a crucial transcription factor for osteoclast differentiation by decreasing c-Fos protein levels and suppressing the activation of p38 and c-Jun-N-terminal kinase. We also identified 12 phytochemicals in WFS including lignans, phenylethanoids, and flavonoids. Collectively, these results suggest that WFS inhibits osteoclast differentiation and can potentially be used to treat postmenopausal osteoporosis.

scholarly journals Anti-Osteoporotic Effects of Commiphora Myrrha and Its Poly-Saccharide via Osteoclastogenesis Inhibition

Plants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 945
Author(s):  
Youn-Hwan Hwang ◽  
Ami Lee ◽  
Taesoo Kim ◽  
Seon-A Jang ◽  
Hyunil Ha
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Nuclear Factor Κb ◽  
Herbal Remedies ◽  
Specific Gene ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Herbal Products ◽  
Marrow Cavity

In traditional oriental medicines, Commiphora myrrha and its resinous exudate (i.e., myrrh) are used as herbal remedies to treat various inflammatory and metabolic disorders. Until now, C. myrrha-derived herbal products are considered useful source for bioactive compounds to manage numerous human diseases. This study investigated the effects of water extract of C. myrrha resin (WCM) and its polysaccharide (WCM-PE) on modulatory effects of osteoclast differentiation and/or ovariectomized-induced bone loss. Oral administration of WCM (200 and 500 mg/kg/day for four weeks) notably decreased trabecular bone loss and lipid accumulation in the bone marrow cavity. WCM and WCM-PE dose-dependently inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis and suppressed RANKL-mediated overexpression of c-Fos and nuclear factor of activated T cells, cytoplasmic 1, thereby downregulating osteoclast-specific gene (Atp6v0d2, DC-STAMP and cathepsin K) expression. Thus, our results suggest that WCM and WCM-PE are promising nutraceutical candidates for the management of osteoporosis in postmenopausal women.

scholarly journals Water Extract of Agastache rugosa Prevents Ovariectomy-Induced Bone Loss by Inhibiting Osteoclastogenesis

Foods ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1181
Author(s):  
Seon-A Jang ◽  
Youn-Hwan Hwang ◽  
Taesoo Kim ◽  
Hyun Yang ◽  
Jun Lee ◽  
...  
Keyword(s):  
Bone Loss ◽  
Postmenopausal Osteoporosis ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Nuclear Factor Κb ◽  
Estrogen Deficiency ◽  
Nuclear Factor ◽  
Agastache Rugosa ◽  
Activated T Cells ◽  
Food Ingredients

Estrogen deficiency in postmenopausal women causes homeostatic imbalance of bone, resulting in bone loss and osteoporosis. Agastache rugosa, a plant belonging to the Lamiaceae family, is an aromatic herb, and the leaves of this herb are widely used as food ingredients. Extracts of A. rugosa have various bioactivities including anti-HIV integration, anti-inflammatory, and anti-atherogenic properties. However, the beneficial effect of A. rugosa on bone has not been studied. Therefore, we investigated the effects of water extract of A. rugosa (WEAR) on osteoclast differentiation and estrogen deficiency-induced bone loss in ovariectomized (OVX) mice as an animal model for postmenopausal osteoporosis. The oral administration of WEAR remarkably improved OVX-induced trabecular bone loss and fat accumulation in the bone marrow. WEAR suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation in osteoclast precursor cells, subsequently inhibiting resorption activity on a bone mimetic surface. WEAR inhibited the expression of cellular oncogene fos (c-Fos) and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), key osteoclastogenic transcription factors, by decreasing RANKL-induced activation of mitogen-activated protein kinases (MAPKs), and nuclear factor-κB (NF-κB) pathways. We also identified seventeen phytochemicals present in WEAR, including five phenols and twelve flavonoids, and found eleven bioactive constituents that have anti-osteoclastogenic effects. Collectively, these results suggest that WEAR could be used to treat and prevent postmenopausal osteoporosis by suppressing osteoclastogenesis.

scholarly journals Water Extract of Mentha arvensis L. Attenuates Estrogen Deficiency-Induced Bone Loss by Inhibiting Osteoclast Differentiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Seon-A Jang ◽  
Youn-Hwan Hwang ◽  
Hyun Yang ◽  
Jin Ah Ryuk ◽  
Taesoo Kim ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Nuclear Factor Κb ◽  
Osteoclast Formation ◽  
Nuclear Factor ◽  
Mentha Arvensis ◽  
Activated T Cells ◽  
Mitogen Activated Protein

Mentha arvensis L., is an aromatic herb that belongs to the Lamiaceae family and is widely used in medicinal applications, essential oil applications, and food flavoring. The extract of M. arvensis has been reported to exert sedative-hypnotic, anti-inflammatory, anti-fungal, and anti-bacterial effects. However, its effects on bone metabolism have not yet been studied. Here, we investigated the effects of the water extract of M. arvensis (WEMA) on osteoclast formation in vitro and bone loss in an ovariectomized mouse model. We found that WEMA inhibited osteoclast differentiation by directly acting on osteoclast precursor cells. WEMA inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced the expression of cellular oncogene fos (c-Fos) and nuclear factor of activated T cells c1 (NFATc1), crucial transcription factors for osteoclast differentiation, by suppressing RANKL-induced activation of early signaling pathways such as those of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB). In addition, oral administration of WEMA suppressed ovariectomy-induced trabecular bone loss in mice. We additionally identified phytochemicals in WEMA that are known to have anti-osteoclastogenic or anti-osteoporotic properties. Collectively, these results suggest that WEMA is a promising herbal candidate that can be used to prevent or treat postmenopausal osteoporosis.

Orostachys japonicus Suppresses Osteoclast Differentiation by Inhibiting NFATc1 Expression

2015 ◽  
Vol 43 (05) ◽  
pp. 1013-1030 ◽  
Author(s):  
Ki-Shuk Shim ◽  
Hyunil Ha ◽  
Taesoo Kim ◽  
Chung-Jo Lee ◽  
Jin Yeul Ma
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Therapeutic Potential ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Bone Diseases ◽  
Tartrate Resistant Acid Phosphatase ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Activated T Cells

The herb Orostachys japonicus has been traditionally used to treat chronic diseases, such as hepatitis, hemorrhoids, and cancer, in Asia. In this study, we investigated the effect of Orostachys japonicus water extract (OJWE) on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone loss. We found that OJWE inhibited RANKL-induced osteoclast differentiation in a dose-dependent manner without affecting bone resorption in bone marrow-derived macrophage cells. Interestingly, OJWE significantly reduced serum levels of C-terminal telopeptide of type 1 collagen and tartrate-resistant acid phosphatase (TRAP) 5b, markers of bone resorption and osteoclast number, respectively, in an animal model of bone loss. Furthermore, OJWE suppressed the RANKL-induced up-regulation of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) expression, and activation of the p38 signaling pathway, but prevented the RANKL-mediated down-regulation of interferon regulatory factor-8 (IRF-8), which is known to be an anti-osteoclastogenic factor that represses NFATc1 expression. We also identified gallic acid and quercetin-3-O-β-D-glucoside as the OJWE components that inhibit RANKL-induced osteoclast differentiation. These results suggest that OJWE inhibits osteoclast differentiation by inhibiting RANKL-induced NFATc1 expression, which prevents osteoclast differentiation and bone loss. The present study elucidated a mechanism of action underlying the inhibitory effect of OJWE on osteoclast differentiation. Our findings suggest that O. japonicus has therapeutic potential for use in the treatment of bone diseases.

scholarly journals Inhibition of Osteoclastogenesis by Thioredoxin-Interacting Protein-Derived Peptide (TN13)

2019 ◽  
Vol 8 (4) ◽  
pp. 431 ◽  
Author(s):  
Mi Kim ◽  
Won Kim ◽  
Jae-Eun Byun ◽  
Jung Choi ◽  
Suk Yoon ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Raw 264.7 Cells ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Interacting Protein ◽  
Hematopoietic Stem ◽  
Thioredoxin Interacting Protein

Overactivated osteoclasts lead to many bone diseases, including osteoporosis and rheumatoid arthritis. The p38 MAPK (p38) is an essential regulator of the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and bone loss. We previously reported TAT conjugated thioredoxin-interacting protein-derived peptide (TAT-TN13) as an inhibitor of p38 in hematopoietic stem cells (HSCs). Here, we examined the role of TAT-TN13 in the differentiation and function of osteoclasts. TAT-TN13 significantly suppressed RANKL-mediated differentiation of RAW 264.7 cells and bone marrow macrophages (BMMs) into osteoclasts. TAT-TN13 also inhibited the RANKL-induced activation of NF-κB and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), leading to the decreased expression of osteoclast-specific genes, including tartrate-resistant acid phosphatase (TRAP) and Cathepsin K. Additionally, TAT-TN13 treatment protected bone loss in ovariectomized (OVX) mice. Taken together, these results suggest that TAT-TN13 inhibits osteoclast differentiation by regulating the p38 and NF-κB signaling pathway; thus, it may be a useful agent for preventing or treating osteoporosis.

scholarly journals Fucoidan Prevents RANKL-Stimulated Osteoclastogenesis and LPS-Induced Inflammatory Bone Loss via Regulation of Akt/GSK3β/PTEN/NFATc1 Signaling Pathway and Calcineurin Activity

Marine Drugs ◽  
2019 ◽  
Vol 17 (6) ◽  
pp. 345 ◽  
Author(s):  
Sheng-Hua Lu ◽  
Yi-Jan Hsia ◽  
Kuang-Chung Shih ◽  
Tz-Chong Chou
Keyword(s):  
Bone Loss ◽  
Molecular Mechanisms ◽  
Bone Erosion ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Calcineurin Activity

Excessive osteoclast differentiation and/or function plays a pivotal role in the pathogenesis of bone diseases such as osteoporosis and rheumatoid arthritis. Here, we examined whether fucoidan, a sulfated polysaccharide present in brown algae, attenuates receptor activator of nuclear factor-κB ligand (RANKL)-stimulated osteoclastogenesis in vitro and lipopolysaccharide (LPS)-induced bone resorption in vivo, and investigated the molecular mechanisms involved. Our results indicated that fucoidan significantly inhibited osteoclast differentiation in RANKL-stimulated macrophages and the bone resorbing activity of osteoclasts. The effects of fucoidan may be mediated by regulation of Akt/GSK3β/PTEN signaling and suppression of the increase in intracellular Ca2+ level and calcineurin activity, thereby inhibiting the translocation of nuclear factor-activated T cells c1 (NFATc1) into the nucleus. However, fucoidan-mediated NFATc1 inactivation was greatly reversed by kenpaullone, a GSK3β inhibitor. In addition, using microcomputer tomography (micro-CT) scanning and bone histomorphometry, we found that fucoidan treatment markedly prevented LPS-induced bone erosion in mice. Collectively, we demonstrated that fucoidan was capable of inhibiting osteoclast differentiation and inflammatory bone loss, which may be modulated by regulation of Akt/GSK3β/PTEN/NFATc1 and Ca2+/calcineurin signaling cascades. These findings suggest that fucoidan may be a potential agent for the treatment of osteoclast-related bone diseases.

scholarly journals Optimized Extract from Corylopsis coreana Uyeki (Hamamelidaceae) Flos Inhibits Osteoclast Differentiation

2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Yongjin Lee ◽  
Jung-Eun Kim ◽  
Kwang-Jin Kim ◽  
Seung-Sik Cho ◽  
Young-Jin Son
Keyword(s):  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Inhibitory Effect ◽  
Osteoclast Formation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Alcoholic Extract ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Fractures Of The Spine ◽  
The Stability

Osteoporosis is a metabolic disorder that decreases the stability against fractures of the spine, femur, and radius by weakening the strength and integrity of bones. Receptor activator of nuclear factor-kappa B ligand signaling ultimately activated nuclear factor-activated T cells c1, a major transcription factor for osteoclast formation. This study researched the effects of Corylopsis coreana (C. coreana) Uyeki flos extracts on the antiosteoclastic potential of macrophages and the phytochemicals contained therein. The alcoholic extract of C. coreana Uyeki flos inhibited the differentiation of osteoclast. We carried out the experiments of the pattern of differentiation of osteoclasts based on the alcoholic percentage of extracts. Among them, 80% alcoholic extract showed the highest inhibitory effect. The alcoholic extract was composed of phytochemicals such as bergenin, quercetin, and quercitrin. This extract inhibited not only mRNA expression levels of NFATc1, osteoclast-associated receptor (OSCAR), cathepsin K, and tartrate-resistant acid phosphatase (TRAP), but also the translational expression of NFATc1. The inhibitory effect for osteoclast differentiation of the alcoholic extract was confirmed using the resorption pit assay. This is the first scientific report of the antiosteoclastic effects of C. coreana Uyeki flos extract, which can be applied therapeutically for the treatment of osteoporosis.

scholarly journals Inhibitory Effects of Gold and Silver Nanoparticles on the Differentiation into Osteoclasts In Vitro

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 462
Author(s):  
Daye Lee ◽  
Wan-Kyu Ko ◽  
Seong Jun Kim ◽  
In-Bo Han ◽  
Je Beom Hong ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Cathepsin K ◽  
Inhibitory Effect ◽  
Tartrate Resistant Acid Phosphatase ◽  
Nuclear Factor ◽  
Inhibitory Effects ◽  
Actin Ring ◽  
Activated T Cells ◽  
Gold And Silver Nanoparticles

Gold nanoparticles (GNPs) have been widely studied to inhibit differentiation into osteoclasts. However, reports of the inhibitory effects of silver nanoparticles (SNPs) during the process of differentiation into osteoclasts are rare. We compared the inhibitory effect of GNPs and SNPs during the process of differentiation into osteoclasts. Bone marrow-derived cells were differentiated into osteoclasts by the receptor activator of the nuclear factor-kappa-Β ligand (RANKL). The inhibitory effect of GNPs or SNPs during the process of differentiation into osteoclasts was investigated using tartrate-resistant acid phosphatase (TRAP) and actin ring staining. The formation of TRAP positive (+) multinuclear cells (MNCs) with the actin ring structure was most inhibited in the SNP group. In addition, the expression of specific genes related to the differentiation into osteoclasts, such as c-Fos, the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), TRAP, and Cathepsin K (CTSK) were also inhibited in the SNP groups. As a result, the levels related to differentiation into osteoclasts were consistently lower in the SNP groups than in the GNP groups. Our study suggests that SNPs can be a useful material for inhibiting differentiation into osteoclasts and they can be applied to treatments for osteoporosis patients.

scholarly journals Water Extract of Lysimachia christinae Inhibits Trabecular Bone Loss and Fat Accumulation in Ovariectomized Mice

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1927
Author(s):  
Ki-Shuk Shim ◽  
Youn-Hwan Hwang ◽  
Seon-A Jang ◽  
Taesoo Kim ◽  
Hyunil Ha
Keyword(s):  
Bone Loss ◽  
Trabecular Bone ◽  
Body Weight Gain ◽  
Osteoclast Differentiation ◽  
Water Extract ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Factor ◽  
Fat Accumulation ◽  
Ovariectomized Mice ◽  
Trabecular Bone Loss

In Asia, extracts of Lysimachia christinae have been used for liver or urinogenital system-related diseases in traditional medicine. In this study, we investigated the effects of the water extract of L. christinae (WELC) on receptor activator of nuclear factor-kappa Β ligand (RANKL)-induced osteoclastic differentiation of bone marrow macrophages, and on osteoporosis and obesity in ovariectomy mice. RANK signaling pathways related to osteoclast differentiation were examined by real-time polymerase chain reaction (PCR) and western blot analysis. Additionally, we performed micro-computed tomography to assess trabecular bone loss, histological analysis for fat accumulation in adipose, liver, and bone tissues, and phytochemical profiling for WELC characterization. WELC significantly inhibited osteoclast differentiation by downregulating RANKL-induced mitogen-activated protein kinase (MAPK)/c-Fos/nuclear factor of activated T-cells (NFAT) signaling in osteoclast precursors and ovariectomy-induced trabecular loss by suppressing osteolcastic bone resorption. WELC markedly decreased ovariectomy-induced body weight gain and fat accumulation in adipose, liver, and bone tissues. Furthermore, ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) identified 16 phytochemicals in WELC when compared with the mass fragmentation of standard chemicals. Collectively, these results suggest that WELC might possess beneficial effects on postmenopausal osteoporosis by inhibiting osteoclast differentiation and obesity by suppressing fat accumulation.

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