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Matías Hernández, Susana Wicz, Ricardo S Corral
BACKGROUND: Diverse cardiovascular signaling routes have been considered critical for Chagas cardiomyopathy caused by the protozoan parasite Trypanosoma cruzi. Along this line, T. cruzi infection and endothelin-1 (ET-1) have been shown to cooperatively activate the Ca(2+)/NFAT cascade in cardiomyocytes, leading to cyclooxygenase type 2 (COX-2) induction and increased release of prostanoids and prohypertrophic peptides. PURPOSE: To determine whether the well-known cardioprotective and anti-inflammatory effects of curcumin (Cur) could be helpful to interfere with this key machinery for pathogenesis of Chagas myocarditis...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Masaaki Ikeda, Yoshitaka Yoshimura, Takashi Kikuiri, Mino Matsuno, Tomokazu Hasegawa, Kumu Fukushima, Takako Hayakawa, Hajime Minamikawa, Kuniaki Suzuki, Junichiro Iida
Bone remodeling is an important factor in orthodontic tooth movement. During orthodontic treatment, osteoclasts are subjected to various mechanical stimuli, and this promotes or inhibits osteoclast differentiation and fusion. It has been previously reported that the release from tensile force induces osteoclast differentiation. However, little is known about how release from compressive force affects osteoclasts. The present study investigated the effects of release from compressive force on osteoclasts. The number of tartrate‑resistant acid phosphatase (TRAP)‑positive multinucleated osteoclasts derived from RAW264...
October 5, 2016: Molecular Medicine Reports
Tengku Siti Hajar Haryuna, Wibi Riawan, Ardyansyah Nasution, Suprapto Ma'at, Juliandi Harahap, Indri Adriztina
Introduction The structural changes underlying permanent noise-induced hearing loss (NIHL) include loss of the sensory hair cells, damage to their stereocilia, and supporting tissues within the cochlear lateral wall. Objective The objective of this study is to demonstrate curcumin as a safe and effective therapeutic agent in the prevention and treatment for fibroblasts damage within the cochlear supporting tissues and lateral wall through cell death pathway. Methods We divided 24 Rattus norvegicus into 4 groups, Group 1: control; Group 2: noise (+); Group 3: noise (+), 50 mg/day curcumin (+); Group 4: noise (+), 100 mg/day curcumin (+)...
October 2016: International Archives of Otorhinolaryngology
Shinya Takigawa, Brian Frondorf, Shengzhi Liu, Yang Liu, Baiyan Li, Akihiro Sudo, Joseph M Wallace, Hiroki Yokota, Kazunori Hamamura
Salubrinal is an agent that reduces the stress to the endoplasmic reticulum by inhibiting de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). We and others have previously shown that the elevated phosphorylation of eIF2α stimulates bone formation and attenuates bone resorption. In this study, we applied salubrinal to a mouse model of osteogenesis imperfecta (Oim), and examined whether it would improve Oim's mechanical property. We conducted in vitro experiments using RAW264.7 pre-osteoclasts and bone marrow derived cells (BMDCs), and performed in vivo administration of salubrinal to Oim (+/-) mice...
October 1, 2016: Journal of Pharmacological Sciences
Jae Ho Choi, Younho Han, Yong An Kim, Sun Woo Jin, Gi Ho Lee, Hyung Min Jeong, Hyun Sun Lee, Young Chul Chung, Young Chun Lee, Eun Ju Kim, Kwang Youl Lee, Hye Gwang Jeong
Platycodon grandiflorum root-derived saponins (Changkil saponins, CKS) are reported to have many pharmacological activities. In our latest research, CKS was proven to have a significant osteogenic effect. However, the detail molecular mechanism of CKS on osteoclastic differentiation has not been fully investigated. Administration of CKS considerably reduced OVX-induced bone loss, and ameliorated the reduction in plasma levels of alkaline phosphatase, calcium, and phosphorus observed in OVX mice. CKS also repressed the deterioration of bone trabecular microarchitecture...
October 14, 2016: Journal of Cellular Biochemistry
Yue Xu, Boyu Yang, Yaguang Hu, Lin Lu, Xi Lu, Jiawei Wang, Qinmeng Shu, Qiaochu Cheng, Shanshan Yu, Fan Xu, Jingjing Huang, Xiaoling Liang
Down syndrome candidate region 1 (DSCR1) has two differentially regulated isoforms (DSCR1-1 and DSCR1-4) and is reported to play a role in a number of physiological processes, such as the inhibition of cardiac hypertrophy, attenuation of angiogenesis and carcinogenesis, and protection against neuronal death. However, the function of DSCR1 in the retina is still not clear. Therefore, we analyzed the expression and location of DSCR1 in the retina of neonatal mice with oxygen-induced retinopathy (OIR), and studied its effects on angiogenesis...
October 12, 2016: Molecular Neurobiology
Shuai Zhao, Yu Sun, Xiaolei Li, Jingcheng Wang, Lianqi Yan, Zhen Zhang, Daxin Wang, Jihang Dai, Jun He, Shuguang Wang
Aseptic prosthetic loosening is a major complication after hip joint replacement. Wear particle-induced periprosthetic osteolysis plays a key role in aseptic prosthetic loosening. Attempting to modulate receptor activator of nuclear factor-κB (RANKL) mediated signaling pathways is a promising strategy to prevent aseptic prosthetic loosening. In the present study, we determined the effect of scutellarin (SCU) on titanium (Ti) particle-induced osteolysis in a mouse calvarial model and RANKL-mediated osteoclastogenesis...
October 8, 2016: International Immunopharmacology
Jong Won Kim, Sung-Kyun Ko, Hye-Min Kim, Gun-Hee Kim, Sangkeun Son, Gil Soo Kim, Gwi Ja Hwang, Eun Soo Jeon, Kee-Sun Shin, In-Ja Ryoo, Young-Soo Hong, Hyuncheol Oh, Kyung Ho Lee, Nak-Kyun Soung, Daisuke Hashizume, Toshihiko Nogawa, Shunji Takahashi, Bo Yeon Kim, Hiroyuki Osada, Jae-Hyuk Jang, Jong Seog Ahn
Two new phenylspirodrimane derivatives, stachybotrysin (1) and stachybotrylactone B (2), were isolated from the cultures of the marine-derived fungus Stachybotrys sp. KCB13F013. The structures were determined by analyzing the spectroscopic data (1D and 2D NMR and MS) and chemical transformation, including the modified Mosher's method and single-crystal X-ray structure analysis. Compound 1 exhibited an inhibitory effect on osteoclast differentiation in bone marrow macrophage cells via suppressing the RANKL-induced activation of p-ERK, p-JNK, p-p38, c-Fos, and NFATc1...
October 11, 2016: Journal of Natural Products
Ya-Hui Chiu, Edward Schwarz, Dongge Li, Yuexin Xu, Tzong-Ren Sheu, Jinbo Li, Karen L de Mesy Bentley, Changyong Feng, Baoli Wang, Jhih-Cheng Wang, Liz Albertorio-Saez, Ronald Wood, Minsoo Kim, Wensheng Wang, Christopher T Ritchlin
DC-STAMP is a multi-pass transmembrane protein essential for cell-cell fusion of osteoclast precursors during osteoclast (OC) development. DC-STAMP-/- mice have mild osteopetrosis and form mononuclear cells with limited resorption capacity. The identification of an Immunoreceptor Tyrosine-based Inhibitory Motif (ITIM) on the cytoplasmic tail of DC-STAMP suggested a potential signaling function but the absence of known DC-STAMP ligand has hindered examination of downstream signaling pathways. To address this problem, we engineered a light-activatable DC-STAMP chimeric molecule in which light exposure mimics ligand engagement that can be traced by downstream Ca2+ signaling...
October 10, 2016: Journal of Cellular Physiology
Jon Andoni Sánchez, Amparo Alfonso, Olivier P Thomas, Luís M Botana
Previous works with autumnalamide reported that Store Operated Calcium (SOC) channels were blocked through mitochondrial modulation. In the present paper we studied the effect of autumnalamide on ionomycin Ca(2+) fluxes. Thus, autumnalamide did not modify ionomycin-sensitive intracellular pools while the ionomycin-induced Ca(2+) influx was blocked with similar potency whether the incubation was done before or after ionomycin-sensitive pools depletion. Nevertheless, autumnalamide was not able to inhibit ionomycin-induced Ca(2+) influx once the membrane channels were activated...
September 28, 2016: Immunobiology
Lan V Pham, Jerry L Bryant, Richard Mendez, Juan Chen, Archito T Tamayo, Zijun Y Xu-Monette, Ken H Young, Ganiraju C Manyam, David Yang, L Jeffrey Medeiros, Richard J Ford
The hexosamine biosynthetic pathway (HBP) requires two key nutrients glucose and glutamine for O-linked N-acetylglucosamine (O-GlcNAc) cycling, a post-translational protein modification that adds GlcNAc to nuclear and cytoplasmic proteins. Increased GlcNAc has been linked to regulatory factors involved in cancer cell growth and survival. However, the biological significance of GlcNAc in diffuse large B-cell lymphoma (DLBCL) is not well defined. This study is the first to show that both the substrate and the endpoint O-GlcNAc transferase (OGT) enzyme of the HBP were highly expressed in DLBCL cell lines and in patient tumors compared with normal B-lymphocytes...
October 3, 2016: Oncotarget
Marc Baud'huin, François Lamoureux, Camille Jacques, Lidia Rodriguez Calleja, Thibaut Quillard, Céline Charrier, Jérome Amiaud, Martine Berreur, Bénédicte Brounais-LeRoyer, Robert Owen, Gwendolen C Reilly, James E Bradner, Dominique Heymann, Benjamin Ory
Histone modifications are important for maintaining the transcription program. BET proteins, an important class of "histone reading proteins", have recently been described as essential in bone biology. This study presents the therapeutic opportunity of BET protein inhibition in osteoporosis. We find that the pharmacological BET protein inhibitor JQ1 rescues pathologic bone loss in a post-ovariectomy osteoporosis model by increasing the trabecular bone volume and restoring mechanical properties. The BET protein inhibition suppresses osteoclast differentiation and activity as well as the osteoblastogenesis in vitro...
September 23, 2016: Bone
Toshifumi Sugatani, Olga A Agapova, Yifu Fang, Alycia G Berman, Joseph M Wallace, Hartmut H Malluche, Marie-Claude Faugere, William Smith, Victoria Sung, Keith A Hruska
Dysregulation of skeletal remodeling is a component of renal osteodystrophy. Previously, we showed that activin receptor signaling is differentially affected in various tissues in chronic kidney disease (CKD). We tested whether a ligand trap for the activin receptor type 2A (RAP-011) is an effective treatment of the osteodystrophy of the CKD-mineral bone disorder. With a 70% reduction in the glomerular filtration rate, CKD was induced at 14 weeks of age in the ldlr-/- high fat-fed mouse model of atherosclerotic vascular calcification and diabetes...
September 22, 2016: Kidney International
Wei Cheng, Kun Yan, Li-Yi Xie, Feng Chen, Hong-Chuan Yu, Yan-Xia Huang, Cheng-Xue Dang
MicroRNAs (miRNAs) are small noncoding RNAs that function in diverse biological processes. However, little is known about the precise role of microRNAs in the functioning of airway smooth muscle cells (ASMCs). Here, we investigated the potential role and mechanisms of the miR-143 -3p on proliferation and the extracellular matrix (ECM) protein production of ASMCs. We demonstrated that miR-143-3p was aberrantly lower in ASMCs isolated from individuals with asthma than in individuals without asthma. Meanwhile, TGF-β1 caused a marked decrease in a time-dependent manner in miR-143-3p expression in ASMCs from asthmatics...
October 2016: Molecular Immunology
Christian H Gabriel, Fridolin Gross, Martin Karl, Heike Stephanowitz, Anna Floriane Hennig, Melanie Weber, Stefanie Gryzik, Ivo Bachmann, Katharina Hecklau, Jürgen Wienands, Johannes Schuchhardt, Hanspeter Herzel, Andreas Radbruch, Eberhard Krause, Ria Baumgrass
Transcription factors of the nuclear factor of activated T cell (NFAT)-family are essential for antigen-specific T cell activation and differentiation. Their cooperative DNA binding with other transcription factors, such as AP1-proteins (FOS, JUN, JUNB), FOXP3, IRFs and EGR1, dictate the gene regulatory action of NFATs. To identify as yet unknown interaction partners of NFAT, we purified biotin tagged NFATc1/αA, NFATc1/βC and NFATc2/C protein-complexes and analyzed their components by SILAC-based mass spectrometry...
September 16, 2016: Journal of Biological Chemistry
Gwangchul Lee, Bora Kim, Youngjong Ko, Mineon Park, Donghwi Kim, Kang Hyeon Ryu, Yong Cheol Jun, Hong Moon Sohn, Wonbong Lim
OBJECTIVE: This study was designed to investigate the effect of 635-nm irradiation from a light emitting diode (LED) on osteoclastogenesis in receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-stimulated mouse bone marrow-derived macrophages (BMMs). We determined whether 635-nm irradiation modulated the RANKL-induced osteoclastic signaling pathway in heat shock protein-27 (HSP27)-silenced cells and analyzed the functional cross talk between these factors in osteoclastic differentiation and activation...
September 14, 2016: Photomedicine and Laser Surgery
Zhao-Fei Li, Li-Hua Cao, Ying Wang, Zhou Zhang, Ming-Wen Fan, Qing-An Xu
OBJECTIVE: To investigate whether intragastric administration of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) could inhibit the bone resorption and inflammation in a mouse calvarial model infected by Porphyromonas gingivalis (P. gingivalis). DESIGN: Live P. gingivalis ATCC 33277 was injected once daily for 6days into the subcutaneous tissue overlying the calvaria in mice. At the same time, 1,25(OH)2D3 (50μg/kg per day) was administered by gavage for 9days, starting 3d before the infection...
August 25, 2016: Archives of Oral Biology
María José Ortuño, Samuel T Robinson, Prakash Subramanyam, Riccardo Paone, Yung-Yu Huang, X Edward Guo, Henry M Colecraft, J John Mann, Patricia Ducy
The use of selective serotonin-reuptake inhibitors (SSRIs) has been associated with an increased risk of bone fracture, raising concerns about their increasingly broader usage. This deleterious effect is poorly understood, and thus strategies to avoid this side effect remain elusive. We show here that fluoxetine (Flx), one of the most-prescribed SSRIs, acts on bone remodeling through two distinct mechanisms. Peripherally, Flx has anti-resorptive properties, directly impairing osteoclast differentiation and function through a serotonin-reuptake-independent mechanism that is dependent on intracellular Ca(2+) levels and the transcription factor Nfatc1...
October 2016: Nature Medicine
Munkhsoyol Erkhembaatar, Dong Ryun Gu, Seoung Hoon Lee, Yu-Mi Yang, Soonhong Park, Shmuel Muallem, Dong Min Shin, Min Seuk Kim
Lysosomal Ca(2+) emerges as a critical component of receptor-evoked Ca(2+) signaling and plays a crucial role in many lysosomal and physiological functions. Lysosomal Ca(2+) release is mediated by the transient receptor potential (TRP) family member TRPML1, mutations that cause the lysosomal storage disease mucolipidosis type 4. Lysosomes play a key role in osteoclast function. However, nothing is known about the role of lysosomal Ca(2+) signaling in osteoclastogenesis and bone metabolism. In this study, we addressed this knowledge gap by studying the role of lysosomal Ca(2+) signaling in osteoclastogenesis, osteoclast and osteoblast functions, and bone homeostasis in vivo...
September 2, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Anubha Mahajan, Aylin R Rodan, Thu H Le, Kyle J Gaulton, Jeffrey Haessler, Adrienne M Stilp, Yoichiro Kamatani, Gu Zhu, Tamar Sofer, Sanjana Puri, Jeffrey N Schellinger, Pei-Lun Chu, Sylvia Cechova, Natalie van Zuydam, Johan Arnlov, Michael F Flessner, Vilmantas Giedraitis, Andrew C Heath, Michiaki Kubo, Anders Larsson, Cecilia M Lindgren, Pamela A F Madden, Grant W Montgomery, George J Papanicolaou, Alex P Reiner, Johan Sundström, Timothy A Thornton, Lars Lind, Erik Ingelsson, Jianwen Cai, Nicholas G Martin, Charles Kooperberg, Koichi Matsuda, John B Whitfield, Yukinori Okada, Cathy C Laurie, Andrew P Morris, Nora Franceschini
We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals...
September 1, 2016: American Journal of Human Genetics
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