Potent inhibitory effect of Foeniculum vulgare Miller extract on osteoclast differentiation and ovariectomy-induced bone loss

In bone homeostasis, bone loss due to excessive osteoclasts and inflammation or osteolysis in the bone formation process cause bone diseases such as osteoporosis. Suppressing the accompanying oxidative stress such as ROS in this process is an important treatment strategy for bone disease. Therefore, in this study, the effect of (2R)-4-(4-hydroxyphenyl)-2-butanol 2-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside (BAG), an arylbutanoid glycoside isolated from Betula platyphylla var. japonica was investigated in RANKL-induced RAW264.7 cells and LPS-stimulated MC3E3-T1 cells. BAG inhibited the activity of TRAP, an important marker of osteoclast differentiation and F-actin ring formation, which has osteospecific structure. In addition, the protein and gene levels were suppressed of integrin β3 and CCL4, which play an important role in the osteoclast-induced bone resorption and migration of osteoclasts, and inhibited the production of ROS and restored the expression of antioxidant enzymes such as SOD and CAT lost by RANKL. The inhibitory effect of BAG on osteoclast differentiation and ROS production appears to be due to the inhibition of MAPKs phosphorylation and NF-κβ translocation, which play a major role in osteoclast differentiation. In addition, BAG inhibited ROS generated by LPS and effectively restores the mineralization of lost osteoblasts, thereby showing the effect of bone formation in the inflammatory situation accompanying bone loss by excessive osteoclasts, suggesting its potential as a new natural product-derived bone disease treatment.

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

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/852648 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 6

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.

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Inhibitory effect of Galgeun-tang on RANKL-induced osteoclast differentiation and bone loss in ovariectomized rats

Biotechnology and Bioprocess Engineering ◽

10.1007/s12257-010-0178-9 ◽

2011 ◽

Vol 16 (1) ◽

pp. 158-166 ◽

Cited By ~ 4

Author(s):

Ki-Shuk Shim ◽

Hwayong Park ◽

Ji-Hye Lee ◽

Choong Je Ma ◽

Sung-Up Choi ◽

...

Keyword(s):

Bone Loss ◽

Osteoclast Differentiation ◽

Inhibitory Effect ◽

Ovariectomized Rats

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Differences in responses to X-ray exposure between osteoclast and osteoblast cells

Journal of Radiation Research ◽

10.1093/jrr/rrx026 ◽

2017 ◽

Vol 58 (6) ◽

pp. 791-802 ◽

Cited By ~ 16

Author(s):

Jian Zhang ◽

Ziyang Wang ◽

Anqing Wu ◽

Jing Nie ◽

Hailong Pei ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Osteoclast Differentiation ◽

Inhibitory Effect ◽

Health Concern ◽

X Rays ◽

Potential Health ◽

X Ray ◽

Radiation Induced ◽

High Doses

Abstract Radiation-induced bone loss is a potential health concern for cancer patients undergoing radiotherapy. Enhanced bone resorption by osteoclasts and decreased bone formation by osteoblasts were thought to be the main reasons. In this study, we showed that both pre-differentiating and differentiating osteoclasts were relatively sensitive to X-rays compared with osteoblasts. X-rays decreased cell viability to a greater degree in RAW264.7 cells and in differentiating cells than than in osteoblastic MC3T3-E1 cells. X-rays at up to 8 Gy had little effects on osteoblast mineralization. In contrast, X-rays at 1 Gy induced enhanced osteoclastogenesis by enhanced cell fusion, but had no effects on bone resorption. A higher dose of X-rays at 8 Gy, however, had an inhibitory effect on bone resorption. In addition, actin ring formation was disrupted by 8 Gy of X-rays and reorganized into clusters. An increased activity of Caspase 3 was found after X-ray exposure. Actin disorganization and increased apoptosis may be the potential effects of X-rays at high doses, by inhibiting osteoclast differentiation. Taken together, our data indicate high radiosensitivity of osteoclasts. X-ray irradiation at relatively low doses can activate osteoclastogenesis, but not osteogenic differentiation. The radiosensitive osteoclasts are the potentially responsive cells for X-ray-induced bone loss.

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A novel BRD4 inhibitor suppresses osteoclastogenesis and ovariectomized osteoporosis by blocking RANKL-mediated MAPK and NF-κB pathways

Cell Death and Disease ◽

10.1038/s41419-021-03939-7 ◽

2021 ◽

Vol 12 (7) ◽

Author(s):

Ying Liu ◽

Wenjie Liu ◽

Ziqiang Yu ◽

Yan Zhang ◽

Yinghua Li ◽

...

Keyword(s):

Bone Loss ◽

Osteoporosis Treatment ◽

Inhibitory Effect ◽

Specific Gene ◽

Actin Ring ◽

Treatment Target ◽

Significant Inhibitory Effect ◽

Promising Treatment

AbstractBromodomain-containing protein 4 (BRD4) has emerged as a promising treatment target for bone-related disorders. (+)-JQ1, a thienotriazolodiazepine compound, has been shown to inhibit pro-osteoclastic activity in a BRD4-dependent approach and impede bone loss caused by ovariectomy (OVX) in vivo. However, clinical trials of (+)-JQ1 are limited because of its poor druggability. In this study, we synthesized a new (+)-JQ1 derivative differing in structure and chirality. One such derivative, (+)-ND, exhibited higher solubility and excellent inhibitory activity against BRD4 compared with its analogue (+)-JQ1. Interestingly, (-)-JQ1 and (-)-ND exhibited low anti-proliferative activity and had no significant inhibitory effect on RANKL-induced osteoclastogenesis as compared with (+)-JQ1 and (+)-ND, suggesting the importance of chirality in the biological activity of compounds. Among these compounds, (+)-ND displayed the most prominent inhibitory effect on RANKL-induced osteoclastogenesis. Moreover, (+)-ND could inhibit osteoclast-specific gene expression, F‐actin ring generation, and bone resorption in vitro and prevent bone loss in OVX mice. Collectively, these findings indicated that (+)-ND represses RANKL‐stimulated osteoclastogenesis and averts OVX-triggered osteoporosis by suppressing MAPK and NF-κB signalling cascades, suggesting that it may be a prospective candidate for osteoporosis treatment.

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Aquatic Toxicity of Photocatalyst Nanoparticles to Green Microalgae Chlorella vulgaris

Water ◽

10.3390/w13010077 ◽

2020 ◽

Vol 13 (1) ◽

pp. 77

Author(s):

Cristina Adochite ◽

Luminita Andronic

Keyword(s):

Chlorella Vulgaris ◽

Advanced Oxidation Process ◽

Growth Parameters ◽

Aquatic Toxicity ◽

Basal Medium ◽

Inhibitory Effect ◽

Synthesis Methods ◽

Potent Inhibitory Effect ◽

Density Surface ◽

The Impact

In the last years, nanoparticles such as TiO2, ZnO, NiO, CuO and Fe2O3 were mainly used in wastewater applications. In addition to the positive aspects concerning using nanoparticles in the advanced oxidation process of wastewater containing pollutants, the impact of these nanoparticles on the environment must also be investigated. The toxicity of nanoparticles is generally investigated by the nanomaterials’ effect on green algae, especially on Chlorella vulgaris. In this review, several aspects are reviewed: the Chlorella vulgaris culture monitoring and growth parameters, the effect of different nanoparticles on Chlorella vulgaris, the toxicity of photocatalyst nanoparticles, and the mechanism of photocatalyst during oxidative stress on the photosynthetic mechanism of Chlorella vulgaris. The Bold basal medium (BBM) is generally recognized as an excellent standard cultivation medium for Chlorella vulgaris in the known environmental conditions such as temperature in the range 20–30 °C and light intensity of around 150 μE·m2·s−1 under a 16/8 h light/dark cycle. The nanoparticles synthesis methods influence the particle size, morphology, density, surface area to generate growth inhibition and further algal deaths at the nanoparticle-dependent concentration. Moreover, the results revealed that nanoparticles caused a more potent inhibitory effect on microalgal growth and severely disrupted algal cells’ membranes.

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Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis

Biomedicines ◽

10.3390/biomedicines9020199 ◽

2021 ◽

Vol 9 (2) ◽

pp. 199

Author(s):

Urara Tanaka ◽

Shunichi Kajioka ◽

Livia S. Finoti ◽

Daniela B. Palioto ◽

Denis F. Kinane ◽

...

Keyword(s):

Dna Methylation ◽

Bone Resorption ◽

Bone Loss ◽

Inflammatory Cytokines ◽

Osteoclast Differentiation ◽

Tartrate Resistant Acid Phosphatase ◽

Dependent Manner ◽

Bone Homeostasis ◽

Osteoblastic Cell Line ◽

Anti Inflammatory

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.

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Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts

Scientific Reports ◽

10.1038/s41598-021-92744-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Tsukasa Tominari ◽

Ayumi Sanada ◽

Ryota Ichimaru ◽

Chiho Matsumoto ◽

Michiko Hirata ◽

...

Keyword(s):

Cell Wall ◽

Bone Loss ◽

Alveolar Bone ◽

Osteoclast Differentiation ◽

Lipoteichoic Acid ◽

Alveolar Bone Loss ◽

Gram Negative Bacteria ◽

Gram Positive ◽

Gram Negative ◽

Gram Positive Bacteria

AbstractPeriodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.

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Osteoclast and osteoblast response to strontium-doped struvite coatings on titanium for improved bone integration

Biomedical Engineering / Biomedizinische Technik ◽

10.1515/bmt-2019-0265 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Claus Moseke ◽

Katharina Wimmer ◽

Markus Meininger ◽

Julia Zerweck ◽

Cornelia Wolf-Brandstetter ◽

...

Keyword(s):

Bone Ingrowth ◽

Osteoclast Differentiation ◽

Inhibitory Effect ◽

Osteoclast Formation ◽

Strontium Nitrate ◽

Bone Implant ◽

Electrochemically Deposited ◽

Bone Integration ◽

Titanium Substrates

AbstractTo develop implants with improved bone ingrowth, titanium substrates were coated with homogeneous and dense struvite (MgNH4PO4·6H2O) layers by means of electrochemically assisted deposition. Strontium nitrate was added to the coating electrolyte in various concentrations, in order to fabricate Sr-doped struvite coatings with Sr loading ranging from 10.6 to 115 μg/cm2. It was expected and observed that osteoclast activity surrounding the implant was inhibited. The cytocompatibility of the coatings and the effect of Sr-ions in different concentrations on osteoclast formation were analyzed in vitro. Osteoclast differentiation was elucidated on morphological, biochemical as well as on gene expression level. It could be shown that moderate concentrations of Sr2+ had an inhibitory effect on osteoclast formation, while the growth of osteoblastic cells was not negatively influenced compared to pure struvite surfaces. In summary, the electrochemically deposited Sr-doped struvite coatings are a promising approach to improve bone implant ingrowth.

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An Anti-Inflammatory 2,4-Cyclized-3,4-Secospongian Diterpenoid and Furanoterpene-Related Metabolites of a Marine Sponge Spongia sp. from the Red Sea

Marine Drugs ◽

10.3390/md19010038 ◽

2021 ◽

Vol 19 (1) ◽

pp. 38

Author(s):

Chi-Jen Tai ◽

Chiung-Yao Huang ◽

Atallah F. Ahmed ◽

Raha S. Orfali ◽

Walied M. Alarif ◽

...

Keyword(s):

Red Sea ◽

Superoxide Anion ◽

Dermal Fibroblast ◽

Fibroblast Cell ◽

Inhibitory Effect ◽

Human Dermal Fibroblast ◽

Superoxide Anion Generation ◽

Potent Inhibitory Effect ◽

Anti Inflammatory ◽

New Compounds

Chemical investigation of a Red Sea Spongia sp. led to the isolation of four new compounds, i.e., 17-dehydroxysponalactone (1), a carboxylic acid, spongiafuranic acid A (2), one hydroxamic acid, spongiafuranohydroxamic acid A (3), and a furanyl trinorsesterpenoid 16-epi-irciformonin G (4), along with three known metabolites (−)-sponalisolide B (5), 18-nor- 3,17-dihydroxy-spongia-3,13(16),14-trien-2-one (6), and cholesta-7-ene-3β,5α-diol-6-one (7). The biosynthetic pathway for the molecular skeleton of 1 and related compounds was postulated for the first time. Anti-inflammatory activity of these metabolites to inhibit superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (fMLF/CB)-induced human neutrophil cells and cytotoxicity of these compounds toward three cancer cell lines and one human dermal fibroblast cell line were assayed. Compound 1 was found to significantly reduce the superoxide anion generation and elastase release at a concentration of 10 μM, and compound 5 was also found to display strong inhibitory activity against superoxide anion generation at the same concentration. Due to the noncytotoxic activity and the potent inhibitory effect toward the superoxide anion generation and elastase release, 1 and 5 can be considered to be promising anti-inflammatory agents.

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