scholarly journals Anti-Osteoporotic Effects of Polysaccharides Isolated from Persimmon Leaves via Osteoclastogenesis Inhibition

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 901 ◽  
Author(s):  
Youn-Hwan Hwang ◽  
Hyunil Ha ◽  
Rajeong Kim ◽  
Chang-Won Cho ◽  
Young-Ran Song ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
In Vivo Model ◽  
Osteoporotic Bone ◽  
Diospyros Kaki ◽  
Nuclear Factor ◽  
Activated T Cells

Persimmon (Diospyros kaki L.f.) leaves have traditionally been used as a phytomedicine, in health beverages to treat cardiovascular and respiratory disease and to promote maternal health in East Asia. In particular, polysaccharides from persimmon are known to have anti-coagulant, anti-oxidant, and immune-stimulatory activities. However, their beneficial effects against osteoporosis have not been reported. In the present study, we investigated the anti-osteoporotic effects of polysaccharides from persimmon leaves (PLE0) using an in vivo model of ovariectomy (OVX)-induced bone loss and an in vitro system of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. In the OVX mouse model, PLE0 remarkably improved OVX-induced trabecular bone loss by suppressing osteoclast activity. In primary bone marrow-derived macrophages (BMMs), PLE0 dose-dependently inhibited osteoclast differentiation. In addition, PLE0 down-regulated RANKL-induced activation of mitogen-activated protein kinases (MAPKs) such as p38, ERK, and JNK resulting in suppression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1) expression. Our results indicate that PLE0 has anti-osteoporotic effects in OVX-induced bone loss via inhibition of osteoclast differentiation. Taken together, PLE0 from persimmon may prevent postmenopausal bone loss and osteoporotic bone fragility.

scholarly journals Transcriptional Modulator Ifrd1 Regulates Osteoclast Differentiation through Enhancing the NF-κB/NFATc1 Pathway

2016 ◽  
Vol 36 (19) ◽  
pp. 2451-2463 ◽  
Author(s):  
Takashi Iezaki ◽  
Kazuya Fukasawa ◽  
Gyujin Park ◽  
Tetsuhiro Horie ◽  
Takashi Kanayama ◽  
...  
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Bone Diseases ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Bone Homeostasis ◽  
Activated T Cells

Bone homeostasis is maintained by the synergistic actions of bone-resorbing osteoclasts and bone-forming osteoblasts. Here, we show that the transcriptional coactivator/repressor interferon-related developmental regulator 1 (Ifrd1) is expressed in osteoclast lineages and represents a component of the machinery that regulates bone homeostasis. Ifrd1 expression was transcriptionally regulated in preosteoclasts by receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) through activator protein 1. Global deletion of murineIfrd1increased bone formation and decreased bone resorption, leading to a higher bone mass. Deletion ofIfrd1in osteoclast precursors prevented RANKL-induced bone loss, although no bone loss was observed under normal physiological conditions. RANKL-dependent osteoclastogenesis was impairedin vitroinIfrd1-deleted bone marrow macrophages (BMMs).Ifrd1deficiency increased the acetylation of p65 at residues K122 and K123 via the inhibition of histone deacetylase-dependent deacetylation in BMMs. This repressed the NF-κB-dependent transcription of nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), an essential regulator of osteoclastogenesis. These findings suggest that an Ifrd1/NF-κB/NFATc1 axis plays a pivotal role in bone remodelingin vivoand represents a therapeutic target for bone diseases.

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.

Berberine Suppresses RANKL-Induced Osteoclast Differentiation by Inhibiting c-Fos and NFATc1 Expression

2019 ◽  
Vol 47 (02) ◽  
pp. 439-455 ◽  
Author(s):  
Sang-Yong Han ◽  
Yun-Kyung Kim
Keyword(s):  
Bone Loss ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Bone Diseases ◽  
Mrna Levels ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Murine Bone Marrow

Osteoporosis is a common disorder of bone remodeling, marked by excessive osteoclast formation. Recent studies indicated that berberine (BBR) is a potential natural drug for the treatment of various bone diseases. However, it still needs to be further studied for the treatment of osteoporosis. The current study investigated the inhibitory effects of BBR on receptor activator of nuclear factor-[Formula: see text]B ligand (RANKL)-induced osteoclast differentiation in vitro and in vivo. Cell-based assays were performed using osteoclasts generated in cultures of murine bone marrow-derived macrophages (BMMs) treated with RANKL and M-CSF. The effects of BBR on in vivo lipopolysaccharide (LPS)-mediated bone loss were evaluated using ICR mice. BBR significantly inhibited TRAP-positive osteoclast formation induced by RANKL. BBR also inhibited RANKL-induced Akt, p38 and ERK phosphorylation and I[Formula: see text]B degradation, and suppressed RANKL-induced expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which is a key transcription factors for osteoclast formation. BBR reduced the mRNA levels of osteoclast markers, including TRAP, osteoclast-associated receptor (OSCAR), cathepsin K, and ATPase H[Formula: see text] transporting V0 subunit d2 (ATP6v0d2). Moreover, BBR prevented LPS-mediated bone loss in vivo. We suggest BBR as a natural compound that can be a potential therapeutic agent for osteoclast-related bone diseases.

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.

scholarly journals Nuclear factor of activated T cells 2 is required for osteoclast differentiation and function in vitro but not in vivo

2018 ◽  
Vol 119 (11) ◽  
pp. 9334-9345 ◽  
Author(s):  
Jungeun Yu ◽  
Stefano Zanotti ◽  
Lauren Schilling ◽  
Ernesto Canalis
Keyword(s):  
T Cells ◽  
Osteoclast Differentiation ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
And Function

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 Eudebeiolide B Inhibits Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Regulating RANKL-Induced NF-κB, c-Fos and Calcium Signaling

2020 ◽  
Vol 13 (12) ◽  
pp. 468
Author(s):  
Mi-Hwa Kim ◽  
Hyung-Jin Lim ◽  
Seon Gyeong Bak ◽  
Eun-Jae Park ◽  
Hyun-Jae Jang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Calcium Signaling ◽  
Osteoblast Differentiation ◽  
Transmembrane Protein ◽  
Osteoclast Differentiation ◽  
Mouse Bone Marrow ◽  
Nuclear Factor ◽  
Mineral Density ◽  
Activated T Cells

Eudebeiolide B is a eudesmane-type sesquiterpenoid compound isolated from Salvia plebeia R. Br., and little is known about its biological activity. In this study, we investigated the effects of eudebeiolide B on osteoblast differentiation, receptor activator nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vitro and ovariectomy-induced bone loss in vivo. Eudebeiolide B induced the expression of alkaline phosphatase (ALP) and calcium accumulation during MC3T3-E1 osteoblast differentiation. In mouse bone marrow macrophages (BMMs), eudebeiolide B suppressed RANKL-induced osteoclast differentiation of BMMs and bone resorption. Eudebeiolide B downregulated the expression of nuclear factor of activated T-cells 1 (NFATc1) and c-fos, transcription factors induced by RANKL. Moreover, eudebeiolide B attenuated the RANKL-induced expression of osteoclastogenesis-related genes, including cathepsin K (Ctsk), matrix metalloproteinase 9 (MMP9) and dendrocyte expressed seven transmembrane protein (DC-STAMP). Regarding the molecular mechanism, eudebeiolide B inhibited the phosphorylation of Akt and NF-κB p65. In addition, it downregulated the expression of cAMP response element-binding protein (CREB), Bruton’s tyrosine kinase (Btk) and phospholipase Cγ2 (PLCγ2) in RANKL-induced calcium signaling. In an ovariectomized (OVX) mouse model, intragastric injection of eudebeiolide B prevented OVX-induced bone loss, as shown by bone mineral density and contents, microarchitecture parameters and serum levels of bone turnover markers. Eudebeiolide B not only promoted osteoblast differentiation but inhibited RANKL-induced osteoclastogenesis through calcium signaling and prevented OVX-induced bone loss. Therefore, eudebeiolide B may be a new therapeutic agent for osteoclast-related diseases, including osteoporosis, rheumatoid arthritis and periodontitis.

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.

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