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Hyun-Ook Jeon, In-Seok Choi, Ji-Young Yoon, Eun-Jung Kim, Ji-Uk Yoon, Ah-Reum Cho, Hyung-Joon Kim, Cheul-Hong Kim
Background: The structure and function of bone tissue is maintained through a constant remodeling process, which is maintained by the balance between osteoblasts and osteoclasts. The failure of bone remodeling can lead to pathological conditions of bone structure and function. Remifentanil is currently used as a narcotic analgesic agent in general anesthesia and sedation. However, the effect of remifentanil on osteoclasts has not been studied. Therefore, we investigated the effect of remifentanil on pre-osteoclast (pre-OCs) differentiation and the mechanism of osteoclast differentiation in the absence of specific stimulus...
February 2018: Journal of Dental Anesthesia and Pain Medicine
Frank Zach, Franziska Polzer, Alexandra Mueller, André Gessner
The sequestosome 1 gene encodes the p62 protein and is the major genetic risk factor associated with Paget's disease of bone. In 2004, p62 was reported to up-regulate osteoclast differentiation by activating the transcription factors Nfatc1 and NF-κB. Here, we characterized the osteoclastogenic potential of murine p62-/- -derived cells compared with WT cells. Our data confirmed previous findings indicating that that p62 is induced during murine osteoclast differentiation. Surprisingly, an indispensable role for p62 in i n vitro osteoclast differentiation was not reproducible, since p62-deficient osteoclasts exhibited robust activation of Nfatc1, NF-κB, and osteoclast marker enzymes...
March 19, 2018: Journal of Biological Chemistry
Jinhua Wang, Wan Li, Xiangjin Zheng, Xiaocong Pang, Guanhua Du
FOXC1 is a vital member of FOX families which play important roles in biological processes including proliferation, differentiation, apoptosis, migration, invasion, metabolism, and longevity. Here we are focusing on roles of FOXC1 and their mechanisms in cancers. FOXC1 promoted progress of many cancers, such as breast cancer (especially basal-like breast cancer), hepatocellular carcinoma, gastric cancer and so on. FOXC1 was also found to be associated with drug resistance of cancers. FOXC1 promoted metastasis of cancers by increasing expression of MMP7, NEDD9 and Snail...
February 23, 2018: Oncotarget
Palani Dinesh, MahaboobKhan Rasool
The current study investigated the therapeutic effect of berberine (BBR), an alkaloid derivative against IL-21/IL-21R mediated phosphotidyl inositol 3 kinase/protein kinase B (PI3K/Akt) signaling in adjuvant induced arthritic fibroblast-like synoviocytes (AA-FLS) isolated from rats and IL-21 mediated osteoclastogenesis in bone-marrow derived monocytes (BMMs). BBR (15-45 µM) treatment attenuated the gene and protein levels of IL-21R complex. BBR suppressed the levels of IL-21 (20 ng/ml) mediated production of inflammatory cytokines such as: tumor necrosis factor alpha (TNFα), interleukin 1 beta (IL-1β), interleukin 6 (IL-6) and interleukin 23 (IL-23) in AA-FLS cells...
March 14, 2018: Cytokine
Ming-Yue Wang, Chang Shen, Meng-Fei An, Chuan-Qi Xie, Xin Wu, Qiang-Qiang Zhu, Bin Sun, Yan-Ping Huang, Yun-Li Zhao, Xuan-Jun Wang, Jun Sheng
AIMS: Dendrobium candidum (DC) and black tea, are traditional chinese drinks, which contain multiple active ingredients. However, whether or not the combination of these two ingredients can improve osteoporosis remains unknown. This study therefore aimed to examine the effects of the combination of DC and black tea extract (BTE) on osteoporosis. MAIN METHODS: Ovariectomy (OVX)-induced osteoporosis in vivo as well as receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis in vitro was selected...
March 12, 2018: Life Sciences
Mei Liu, Xiaotian Zhou, Lin Zhou, Zhenzhou Liu, Jinbo Yuan, Jianwen Cheng, Jinmin Zhao, Longfei Wu, Hui Li, Haiwen Qiu, Jiake Xu
The discovery of new therapeutic drugs with the ability of preventing inflammation and joint destruction with less adverse effects is urgently needed for rheumatoid arthritis (RA). Carnosic acid (CA), a major phenolic compound isolated from the leaves of Rosemary (Rosmarinus officinalis L.), has been reported to have antioxidative and antimicrobial properties. However, its effects on RA have not been elucidated. Here, we investigated the effects of CA on osteoclasts and fibroblast-like synoviocytes in vitro and on collagen-induced arthritis (CIA) in Wistar rats in vivo...
March 9, 2018: Journal of Cellular Physiology
Mithun Ghosh, In Sook Kim, Young Min Lee, Seong Min Hong, Taek Hwan Lee, Ji Hong Lim, Trishna Debnath, Beong Ou Lim
This study aimed to determine the anti-osteoclastogenic effects of extracts from Aronia melanocarpa 'Viking' (AM) and identify the underlying mechanisms in vitro. Reactive oxygen species (ROS) are signal mediators in osteoclast differentiation. AM extracts inhibited ROS production in RAW 264.7 cells in a dose-dependent manner and exhibited strong radical scavenging activity. The extracts also attenuated the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts. To attain molecular insights, the effect of the extracts on the signaling pathways induced by receptor activator of nuclear factor kappa B ligand (RANKL) were also investigated...
March 8, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Sabrina Giampaolo, Gabriela Wójcik, Stefan Klein-Hessling, Edgar Serfling, Amiya K Patra
The role of NFAT family transcription factors in erythropoiesis is so far unknown, although their involvement has been suggested previously. We have shown recently that Il2 -/- mice develop severe anemia due to defects in KLF1 activity during BM erythropoiesis. Although, KLF1 activity is indispensable for erythropoiesis, the molecular details of Klf1 expression have not yet been elucidated. Here we show that an enhanced NFATc1 activity induced by increased integrin-cAMP signaling plays a critical role in the dysregulation of Klf1 expression and thereby cause anemia in Il2 -/- mice...
February 9, 2018: Oncotarget
Shengzhi Liu, Yang Liu, Kazumasa Minami, Andy Chen, Qiaoqiao Wan, Yukun Yin, Liangying Gan, Aihua Xu, Nariaki Matsuura, Masahiko Koizumi, Yunlong Liu, Sungsoo Na, Jiliang Li, Harikrishna Nakshatri, Bai-Yan Li, Hiroki Yokota
DNA damage response plays a critical role in tumor growth, but little is known about its potential role in bone metabolism. We employed selective inhibitors of Chk1 and examined their effects on the proliferation and migration of mammary tumor cells as well as the development of osteoblasts and osteoclasts. Further, using a mouse model of bone metastasis we evaluated the effects of Chk1 inhibitors on bone quality. Chk1 inhibitors blocked the proliferation, survival, and migration of tumor cells in vitro and suppressed the development of bone-resorbing osteoclasts by downregulating NFATc1...
February 6, 2018: Oncotarget
Elena A Pudova, Anna V Kudryavtseva, Maria S Fedorova, Andrew R Zaretsky, Dmitry S Shcherbo, Elena N Lukyanova, Anatoly Y Popov, Asiya F Sadritdinova, Ivan S Abramov, Sergey L Kharitonov, George S Krasnov, Kseniya M Klimina, Nadezhda V Koroban, Nadezhda N Volchenko, Kirill M Nyushko, Nataliya V Melnikova, Maria A Chernichenko, Dmitry V Sidorov, Boris Y Alekseev, Marina V Kiseleva, Andrey D Kaprin, Alexey A Dmitriev, Anastasiya V Snezhkina
BACKGROUND: Colorectal cancer (CRC) is a common cancer worldwide. The main cause of death in CRC includes tumor progression and metastasis. At molecular level, these processes may be triggered by epithelial-mesenchymal transition (EMT) and necessitates specific alterations in cell metabolism. Although several EMT-related metabolic changes have been described in CRC, the mechanism is still poorly understood. RESULTS: Using CrossHub software, we analyzed RNA-Seq expression profile data of CRC derived from The Cancer Genome Atlas (TCGA) project...
February 9, 2018: BMC Genomics
Qiang Wang, Yongjian Zhao, Nannan Sha, Yan Zhang, Chenguang Li, Hao Zhang, Dezhi Tang, Sheng Lu, Qi Shi, Yongjun Wang, Bing Shu, Dongfeng Zhao
Primary osteoporosis (POP), which is caused by unbalanced bone remodeling, leads to significant economic and societal burdens globally. Gushukang (GSK) granule serves as one commonly used prescription for POP in Traditional Chinese Medicine (TCM). The present study aimed to clarify the exact roles of GSK in bone remodeling with in vivo and in vitro assays. Here we showed that GSK prevented bone loss and the alternations of osteoporotic bone parameters as well as the decreased density of osteoclast in ovariectomized (OVX) mice...
February 10, 2018: Journal of Pharmacological Sciences
Bo Qu, Kai Gong, Hongsheng Yang, Yugang Li, Tao Jiang, Zhimou Zeng, Zongrui Cao, Xianming Pan
Findings concerning the role of diabetes mellitus (DM) in osteoclast differentiation are contradictory in vivo and in vitro. Sirtuin 1 (SIRT1) can inhibit RANKL-induced osteoclastogenesis and deacetylate p66Shc suppress its phosphorylation in high glucose (HG)-stimulated human umbilical vein endothelial cells. This study aimed to investigate the role and mechanism of SIRT1 in DM-related osteoclast differentiation. Osteoclast precursors were cultured with HG and palmitate (PA), with or without resveratrol/sirtinol...
February 24, 2018: Molecular and Cellular Endocrinology
Kiryeong Kim, Tae Hoon Kim, Hye Jung Ihn, Jung Eun Kim, Je-Yong Choi, Hong-In Shin, Eui Kyun Park
Purpurogallin, a benzotropolone-containing natural compound, has been reported to exhibit numerous biological and pharmacological functions, such as antioxidant, anticancer, and anti-inflammatory effects. In this study, we enzymatically synthesized purpurogallin from pyrogallol and investigated its role in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Purpurogallin attenuated the formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts from bone marrow macrophages (BMMs) without causing cytotoxicity, and suppressed upregulation of osteoclast-specific markers, including TRAP (Acp5), cathepsin K (Ctsk), and dendritic cell-specific transmembrane protein (Dcstamp)...
February 17, 2018: International Journal of Molecular Sciences
Rongjing Zhou, Lili Shen, Chengzhe Yang, Limei Wang, Hongmei Guo, Pishan Yang, Aimei Song
Periodontitis has been advocated as a systematic chronic low-grade infection burden. However, the relationship between periodontitis and bone defect healing has not been elucidated. One hundred and eight male Wister rats were randomly assigned into three groups: control (healthy) group, periodontitis group, and periodontitis plus human tumor necrosis factor receptorII:IgG Fc fusion protein (rhTNFR:Fc) group. The experimental periodontitis model was established by ligaturing with orthodontic wire and silk suture plus local administration of 20 μl of lipopolysaccharide (LPS)...
February 19, 2018: Inflammation
J H Kang, H Jung, M Yim
Osteoclasts, which are specialized bone multinuclear cells, are responsible for bone lytic diseases such as osteoporosis. 3',4',7,8-tetrahydroxyflavone is a flavonoid from Acacia confusa. In the present study, we found that 3',4',7,8-tetrahydroxyflavone markedly inhibited receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastic differentiation from mouse bone marrow-derived macrophages (BMMs). 3',4',7,8-tetrahydroxyflavone also reduced the mRNA expression levels of osteoclastic marker genes including the calcitonin receptor (CTR) and cathepsin K...
March 1, 2017: Die Pharmazie
Eunson Hwang, Hien T T Ngo, Seul A Seo, Bom Park, Mengyang Zhang, Tae-Hoo Yi
BACKGROUND: Alchemilla mollis (lady's mantle) is a common ingredient in skin care products. However, the protective mechanism of A. mollis against skin problems has not been elucidated. PURPOSE: This study was to investigate the effects of A. mollis ethanolic extract (AM) on UVB-irradiated normal human dermal fibroblasts (NHDF) and hairless mice. METHODS: The in vitro anti-photoaging effect of AM was performed in NHDFs. The antioxidant activities were assessed through DPPH, ABTS, and reactive oxygen species (ROS) assays...
January 15, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Zhongqi Li, Wenzhi Zhang, Yan Huang
The important role of miR-133a in the progress and development of postmenopausal osteoporosis has been reported, however, the underlying mechanism is not clear yet. In this study, qRT-PCR analysis was performed to assess miR-133 expression in serum isolated from postmenopausal osteoporosis patients (PMOP) and healthy controls. Bone mineral density (BMD) was measured at the lumbar spine by dual-energy X-ray absorptiometry (DXA). The results showed that miR-133a was significantly upregulated and negatively correlated with lumbar spine BMD in serum of postmenopausal osteoporotic women...
February 7, 2018: Acta Biochimica et Biophysica Sinica
Zhengxiao Ouyang, Xiaoning Guo, Xia Chen, Bo Liu, Qiang Zhang, Ziqing Yin, Zanjing Zhai, Xinhua Qu, Xuqiang Liu, Dan Peng, Yi Shen, Tang Liu, Qing Zhang
Bone is the most common target organ of metastasis of breast cancers. This produces considerable morbidity due to skeletal-related events, and severely reduces the quality of life. Increased osteoclast activity is implicated in breast cancer outgrowth in the bone microenvironment. Our previous observation of an anti-osteoclastic activity of hypericin, a natural plant compound, led us to investigate whether hypericin could inhibit bone metastasis and osteolysis caused by breast cancer. We find that hypericin inhibited the upregulation of osteoclasts stimulated by breast cancer cells...
January 5, 2018: Oncotarget
Khalid Muhammad, Ronald Rudolf, Duong Anh Thuy Pham, Stefan Klein-Hessling, Katsuyoshi Takata, Nobuko Matsushita, Volker Ellenrieder, Eisaku Kondo, Edgar Serfling
In lymphocytes, immune receptor signals induce the rapid nuclear translocation of preformed cytosolic NFAT proteins. Along with co-stimulatory signals, persistent immune receptor signals lead to high levels of NFATc1/αA, a short NFATc1 isoform, in effector lymphocytes. Whereas NFATc1 is not expressed in plasma cells, in germinal centers numerous centrocytic B cells express nuclear NFATc1/αA. When overexpressed in chicken DT40 B cells or murine WEHI 231 B cells, NFATc1/αA suppressed their cell death induced by B cell receptor signals and affected the expression of genes controlling the germinal center reaction and plasma cell formation...
2018: Frontiers in Immunology
Yugai Jia, Yumeng Miao, Mengfan Yue, Mei Shu, Zhifeng Wei, Yue Dai
Tetrandrine, a bisbenzylisoquinoline alkaloid, was previously demonstrated to attenuate inflammation and cartilage destruction in the ankles of mice with collagen-induced arthritis (CIA). Here, we explored the underlying mechanism by which tetrandrine prevented arthritis-induced bone erosion by focusing on the differentiation and function of osteoclasts. We found that daily administration of tetrandrine (30 mg/kg) markedly reduced the bone damage and decreased the number of osteoclasts in CIA rats. In vitro, tetrandrine inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis at the early stage and reduced the expressions of osteoclast-related marker genes...
January 30, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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