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L X Zhang, Y M Balani, Sophia Trinh, Henry M Kronenberg, Yiming Mu
Objective: To investigate the distinct effects of intermittent and continuous administration of parathyroid hormone (PTH) on bone and mesenchymal stem cell (MSC). Methods: Six weeks old mice with C57/BL6J background and SOX9-creERT/Td-tomato/Osteocalcin-GFP genotype were divided into 6 groups: intermittent administration and withdraw group (subcutaneous injection with PTH 500 μg·kg-1 ·d-1 ), continuous administration and withdraw group (subcutaneous implantation of PTH pump, 80 μg·kg-1 ·d-1, with a rate of 0...
March 13, 2018: Zhonghua Yi Xue za Zhi [Chinese medical journal]
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
Hui Jiang, Yicun Wang, Zhantao Deng, Jiewen Jin, Jia Meng, Shuo Chen, Jun Wang, Yang Qiu, Ting Guo, Jianning Zhao
Wear particle-induced osteolysis is a major cause of aseptic loosening in arthroplasty failure, but the underlying mechanism remains unclear. Due to long follow-ups necessary for detection and sporadic occurrence, it is challenging to assess the pathogenesis ofparticle-induced osteolysis in clinical cases. Hence, optimal animal models are required for further studies. The murine model of calvarial osteolysis established by exposure to CoCrMo particles is an effective and valid tool for assessing the interactions between particles and various cells in aseptic loosening...
February 17, 2018: Journal of Visualized Experiments: JoVE
Tanya B Dorff, Neeraj Agarwal
Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA...
March 16, 2018: Asian Journal of Andrology
Ya-Ping Xiao, Jie Zeng, Lin-Na Jiao, Xiao-Yu Xu
The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Miyuki Kuno
A proton is a ubiquitous signaling ion. Many transmembrane H+ transport pathways either maintain pH homeostasis or generate acidic compartments. The osteoclast is a bone-resorbing cell, which degrades bone tissues by secreting protons and lysosomal enzymes into the resorption pit. The plasma membrane facing bone tissue (ruffled border), generated partly by fusion of lysosomes, may mimic H+ flux mechanisms regulating acidic vesicles. We identified three electrogenic H+ -fluxes in osteoclast plasma membranes-a vacuolar H+ -ATPase (V-ATPase), a voltage-gated proton channel (Hv channel) and an acid-inducible H+ -leak-whose electrophysiological profiles and regulation mechanisms differed...
March 17, 2018: Pflügers Archiv: European Journal of Physiology
Hema Kalyanaraman, Nadine Schall, Renate B Pilz
Nitric oxide plays a central role in the regulation of skeletal homeostasis. In cells of the osteoblastic lineage, NO is generated in response to mechanical stimulation and estrogen exposure. Via activation of soluble guanylyl cyclase (sGC) and cGMP-dependent protein kinases (PKGs), NO enhances proliferation, differentiation, and survival of bone-forming cells in the osteoblastic lineage. NO also regulates the differentiation and activity of bone-resorbing osteoclasts; here the effects are largely inhibitory and partly cGMP-independent...
March 14, 2018: Nitric Oxide: Biology and Chemistry
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
Shuhei Kajikawa, Yuu Taguchi, Tadayoshi Hayata, Yoichi Ezura, Ryo Ueta, Sumimasa Arimura, Jun-Ichiro Inoue, Masaki Noda, Yuji Yamanashi
Bone mass is determined by coordinated acts of osteoblasts and osteoclasts, which control bone formation and resorption, respectively. Osteoclasts are multinucleated, macrophage/monocyte lineage cells from bone marrow. The Dok-family adaptors Dok-1, Dok-2 and Dok-3 are expressed in the macrophage/monocyte lineage and negatively regulate many signaling pathways, implying roles in osteoclastogenesis. Indeed, mice lacking Dok-1 and Dok-2, the closest homologues with redundant functions, develop osteopenia with increased osteoclast counts compared to the wild-type controls...
March 16, 2018: Biochemical and Biophysical Research Communications
Caterina Musolino, Giacomo Oteri, Alessandro Allegra, Manuela Mania, Angela D'Ascola, Angela Avenoso, Vanessa Innao, Andrea Gaetano Allegra, Salvatore Campo
Bisphosphonates are formidable inhibitors of osteoclast-mediated bone resorption employed for therapy of multiple myeloma (MM) subjects with osteolytic lesions. Osteonecrosis of the jaw (ONJ) is an uncommon drug-induced adverse event of these agents. MicroRNAs (miRNAs) are a group of small, noncoding RNAs nucleotides, which are essential post-transcriptional controllers of gene expression. They have a central role in the normal bone development. The goal of our study was to investigate 18 miRNAs, whose targets were previously validated and described in MM subjects without ONJ, in peripheral lymphocytes of MM subjects with bisphosphonate-induced ONJ...
March 15, 2018: Annals of Hematology
Jun Bian, Dan Cao, Jie Shen, Bo Jiang, Dan Chen, Lanzheng Bian
N-methyl pyrrolidone (NMP), a small bioactive molecule, has the potential to stimulate bone formation and inhibit osteoclast differentiation. The aim of the present study was to investigate the effect of NMP on the inflammatory response and underlying molecular mechanisms in MG-63 cells. The mRNA and protein expression of cytokines from peripheral blood in children with or without ankle fracture were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and ELISA, respectively...
April 2018: Experimental and Therapeutic Medicine
Clément Cochain, Ehsan Vafadarnejad, Panagiota Arampatzi, Pelisek Jaroslav, Holger Winkels, Klaus Ley, Dennis Wolf, Antoine-Emmanuel Saliba, Alma Zernecke
<u>Rationale:</u> It is assumed that atherosclerotic arteries contain several macrophage subsets endowed with specific functions. The precise identity of these subsets is poorly characterized as they ha ve been defined by the expression of a restricted number of markers. <u>Objective:</u> We have applied single-cell RNA-seq as an unbiased profiling strategy to interrogate and classify aortic macrophage heterogeneity at the single-cell level in atherosclerosis. <u>Methods and Results:</u> We performed single-cell RNA sequencing of total aortic CD45+ cells extracted from the non-diseased (chow fed) and atherosclerotic (11 weeks of high fat diet) aorta of Ldlr-/- mice...
March 15, 2018: Circulation Research
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
Mothanna K AlRahabi, Hani M Ghabbani
Bisphosphonates are stable structural analogs of pyrophosphate, which suppress the activity of osteoclasts, leading to decreased bone resorption. They are essential medications in the treatment of osteoporosis. Osteonecrosis of the jaw is a serious adverse effect of bisphosphonate therapy. The prevalence of bisphosphonate-related osteonecrosis of the jaw varies from 0% to 28%, and it can be triggered by dental extraction and trauma. Root canal therapy can delay, or even eliminate, the need for tooth extraction, and therefore, may reduce the risk of bisphosphonate-related osteonecrosis of the jaw...
March 2018: Saudi Medical Journal
Eiki Yoshida, Takafumi Suzuki, Masanobu Morita, Keiko Taguchi, Kohei Tsuchida, Hozumi Motohashi, Minoru Doita, Masayuki Yamamoto
Keap1 is a negative regulator of Nrf2, a master transcription factor that regulates cytoprotection against oxidative and electrophilic stresses. Although several studies have suggested that the Keap1-Nrf2 system contributes to bone formation besides the maintenance of redox homeostasis, how Nrf2 hyperactivation by Keap1 deficiency affects the bone formation remains to be explored, as the Keap1-null mice are juvenile lethal. To overcome this problem, we used viable Keap1-deficient mice that we have generated by deleting the esophageal Nrf2 in Keap1-null mice (NEKO mice)...
March 15, 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Cheol-Jung Lee, Su-Jin Moon, Jeong-Hee Jeong, Sangbae Lee, Mee-Hyun Lee, Sun-Mi Yoo, Hye Suk Lee, Han Chang Kang, Joo Young Lee, Weon Sun Lee, Hee-Jin Lee, Eun-Kyung Kim, Joo-Yeon Jhun, Mi-La Cho, Jun-Ki Min, Yong-Yeon Cho
Rheumatoid arthritis (RA) is a systemic inflammatory disease that mainly affects the synovial joints. Although involvement of the fibroblast growth factor (FGF) signaling pathway has been suggested as an important modulator in RA development, no clear evidence has been provided. In this study, we found that synovial fluid basic FGF (bFGF) concentration was significantly higher in RA than in osteoarthritis (OA) patients. bFGF stimulates proliferation and migration of human fibroblast-like synoviocytes (FLSs) by activation of the bFGF-FGF receptor 3 (FGFR3)-ribosomal S6 kinase 2 (RSK2) signaling axis...
March 14, 2018: Cell Death & Disease
Sun-Ju Yi, Kyunghwan Kim
Chromatin is an intelligent building block that can express either external or internal needs through structural changes. To date, three methods to change chromatin structure and regulate gene expression have been well-documented: histone modification, histone exchange, and ATP-dependent chromatin remodeling. Recently, a growing body of literature has suggested that histone tail cleavage is related to various cellular processes including stem cell differentiation, osteoclast differentiation, granulocyte differentiation, mammary gland differentiation, viral infection, aging, and yeast sporulation...
March 15, 2018: BMB Reports
A A Alhasyimi, P P Pudyani, W Asmara, I D Ana
OBJECTIVE: To evaluate the effect of carbonated hydroxyapatite-incorporated advanced platelet-rich fibrin on relapse and bone remodelling in rabbits. MATERIALS AND METHODS: Forty-five rabbits were divided into 3 groups (n = 15): a control group, carbonated hydroxyapatite (CHA) and carbonated hydroxyapatite-incorporated advanced platelet-rich fibrin (CHA-aPRF) group. The lower incisors were subjected to an orthodontic force of 50 cN. During the retention period, CHA and CHA-aPRF hydrogel were gently injected in the mesial gingival sulcus every 7 days...
March 14, 2018: Orthodontics & Craniofacial Research
Shuping Peng, Lihua Cao, Shiwei He, Yancheng Zhong, Haotian Ma, Yanru Zhang, Cijun Shuai
Bone regeneration is very important for the recovery of some diseases including osteoporosis and bone fracture trauma. It is a multiple-step- and multiple-gene-involved complex process, including the matrix secretion and calcium mineralization by osteoblasts differentiated from mesenchymal stem cells (MSCs) and the absorption of calcium and phosphorus by osteoclasts differentiated from hematopoietic stem cells. Long noncoding RNAs (lncRNAs) are a family of transcripts longer than 200 nt without or with very low protein-coding potential...
2018: Stem Cells International
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