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https://www.readbyqxmd.com/read/27905067/mathematical-model-of-bone-remodeling-captures-the-antiresorptive-and-anabolic-actions-of-various-therapies
#1
David S Ross, Khamir Mehta, Antonio Cabal
A better understanding of the molecular pathways regulating the bone remodeling process should help in the development of new antiresorptive regulators and anabolic regulators, that is, regulators of bone resorption and of bone formation. Understanding the mechanisms by which parathyroid hormone (PTH) influences bone formation and how it switches from anabolic to catabolic action is important for treating osteoporosis (Poole and Reeve in Curr Opin Pharmacol 5:612-617, 2005). In this paper we describe a mathematical model of bone remodeling that incorporates, extends, and integrates several models of particular aspects of this biochemical system (Cabal et al...
November 30, 2016: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/27812916/gabab-receptors-as-modulating-target-for-inflammatory-responses-of-the-periodontal-ligament
#2
Anna Konermann, Thomas Van Dyke, Alpdogan Kantarci, Andreas Jäger
PDL cells express GABAB1 and GABAB2 receptors, which are regulated by inflammation and thus might be implicated in periodontal immunology. It was the aim of this study to elucidate the functional role of GABAB receptors in immunomodulation regarding activation of proregenerative versus proinflammatory mechanisms. Human PDL cells were exposed to GABA and/or GABAB receptor antagonist CGP-52432 alone or in combination with IL-1β to mimic inflammation. The influence on marker expression for inflammatory tissue destruction was determined via qRT-PCR and Luminex assays...
November 3, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27776430/baicalein-promotes-angiogenesis-and-odontoblastic-differentiation-via-the-bmp-and-wnt-pathways-in-human-dental-pulp-cells
#3
Sang-Im Lee, Sun-Young Kim, Kyung-Ran Park, Eun-Cheol Kim
Baicalein is an active flavonoid extracted from the root of Scutellaria baicalensis that has anticancer and anti-inflammatory properties; its effects on osteoblastic and angiogenic potential are controversial. The aim of this study was to investigate the effects of baicalein on odontoblastic differentiation and angiogenesis and the underlying mechanism in human dental pulp cells (HDPCs). Baicalein (1-10[Formula: see text][Formula: see text]M) had no cytotoxic effects and promoted alkaline phosphatase (ALP) activity, mineralization assayed by Alizarin Red-S staining, and the mRNA expression of marker genes, in a concentration-dependent manner...
October 25, 2016: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/27764190/substance-p-promotes-the-proliferation-but-inhibits-differentiation-and-mineralization-of-osteoblasts-from-rats-with-spinal-cord-injury-via-rankl-opg-system
#4
Hai-Juan Liu, Hua Yan, Jun Yan, Hao Li, Liang Chen, Li-Ren Han, Xiao-Fei Yang
Spinal cord injury (SCI) causes a significant amount of bone loss, which results in osteoporosis (OP). The neuropeptide substance P (SP) and SP receptors may play important roles in the pathogenesis of OP after SCI. To identify the roles of SP in the bone marrow mesenchymal stem cell derived osteoblasts (BMSC-OB) in SCI rats, we investigated the expression of neurokinin-1 receptors (NK1R) in BMSC-OB and the effects of SP on bone formation by development of BMSC-OB cultures. Sixty young male Sprague-Dawley rats were randomized into two groups: SHAM and SCI...
2016: PloS One
https://www.readbyqxmd.com/read/27586506/a-comparative-study-on-the-efficacies-of-gonadotropin-releasing-hormone-gnrh-agonist-and-gnrh-antagonist-in-neoadjuvant-androgen-deprivation-therapy-combined-with-transperineal-prostate-brachytherapy-for-localized-prostate-cancer
#5
Kenta Miki, Hiroshi Sasaki, Masahito Kido, Hiroyuki Takahashi, Manabu Aoki, Shin Egawa
BACKGROUND: Neoadjuvant androgen deprivation therapy (ADT) has been suggested to confer several clinical benefits in patients with prostate cancer (PCa) undergoing transperineal prostate brachytherapy (TPPB). Unlike gonadotropin-releasing hormone (GnRH) receptor agonists, a GnRH antagonist such as degarelix can achieve castrate levels of testosterone without testosterone flare. However, normalization of serum testosterone levels following completion of neoadjuvant ADT in either form of treatment has never been compared in clinical trials...
September 1, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27581523/peripheral-serotonin-mediated-system-suppresses-bone-development-and-regeneration-via-serotonin-6-g-protein-coupled-receptor
#6
Hyung-Mun Yun, Kyung-Ran Park, Jin Tae Hong, Eun-Cheol Kim
Serotonin is important in brain functions and involved in neurological diseases. It is also drawn considerable attention in bone disease since it mainly produced by the gut. Serotonin 6 G-protein-coupled receptor (5-HT6R) is clinical targets for the treatment of neurological diseases. However, 5-HT6R as a therapeutic target in bone has not been reported. Herein, we found that 5-HT6R showed higher expression in bone, and its expression was increased during bone remodeling and osteoblast differentiation. The activation of 5-HT6R by ST1936 caused the inhibition of ALP activity and mineralization in primary osteoblast cultures, which was antagonized by SB258585, an antagonist and by the knockdown of 5-HT6R...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27494172/circadian-rhythm-regulates-development-of-enamel-in-mouse-mandibular-first-molar
#7
Jiang Tao, Yue Zhai, Hyun Park, Junli Han, Jianhui Dong, Ming Xie, Ting Gu, Keidren Lewi, Fang Ji, William Jia
Rhythmic incremental growth lines and the presence of melatonin receptors were discovered in tooth enamel, suggesting possible role of circadian rhythm. We therefore hypothesized that circadian rhythm may regulate enamel formation through melatonin receptors. To test this hypothesis, we examined expression of melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation, during tooth germ development in mouse. Using qRT-PCR and immunocytochemistry, we found that mRNA and protein levels of both MTs and AMELX in normal mandibular first molar tooth germs increased gradually after birth, peaked at 3 or 4 day postnatal, and then decreased...
2016: PloS One
https://www.readbyqxmd.com/read/27468810/diabetes-stimulates-osteoclastogenesis-by-acidosis-induced-activation-of-transient-receptor-potential-cation-channels
#8
Carlotta Reni, Giuseppe Mangialardi, Marco Meloni, Paolo Madeddu
Patients with type 1 diabetes have lower bone mineral density and higher risk of fractures. The role of osteoblasts in diabetes-related osteoporosis is well acknowledged whereas the role of osteoclasts (OCLs) is still unclear. We hypothesize that OCLs participate in pathological bone remodeling. We conducted studies in animals (streptozotocin-induced type 1 diabetic mice) and cellular models to investigate canonical and non-canonical mechanisms underlying excessive OCL activation. Diabetic mice show an increased number of active OCLs...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27325243/skeletal-effects-of-a-gastrin-receptor-antagonist-in-h-k-atpase-beta-subunit-ko-mice
#9
Kristin M Aasarød, Masoud Ramezanzadehkoldeh, Maziar Shabestari, Mats P Mosti, Astrid K Stunes, Janne E Reseland, Vidar Beisvag, Erik Fink Eriksen, Arne K Sandvik, Reinhold G Erben, Christiane Schüler, Malcolm Boyce, Bjørn H Skallerud, Unni Syversen, Reidar Fossmark
Epidemiological studies suggest an increased fracture risk in patients taking proton pump inhibitors (PPIs) for long term. The underlying mechanism, however, has been disputed. By binding to the gastric proton pump, PPIs inhibit gastric acid secretion. We have previously shown that proton pump (H(+)/K(+)ATPase beta subunit) KO mice exhibit reduced bone mineral density (BMD) and inferior bone strength compared with WT mice. Patients using PPIs as well as these KO mice exhibit gastric hypoacidity, and subsequently increased serum concentrations of the hormone gastrin...
August 2016: Journal of Endocrinology
https://www.readbyqxmd.com/read/27174746/allatostatin-c-antagonizes-the-synergistic-myostimulatory-effect-of-allatotropin-and-serotonin-in-rhodnius-prolixus-stal
#10
María José Villalobos-Sambucaro, Luis Anibal Diambra, Fernando Gabriel Noriega, Jorge Rafael Ronderos
Haematophagous insects can ingest large quantities of blood in a single meal producing a large quantity of urine in the following hours to eliminate the excess of water and mineral ions incorporated. The excretory activity of the Malpighian tubules is facilitated by an increase in haemolymph circulation as a result of the intensification of aorta contractions, combined with an increase of anterior midgut peristaltic waves. We have recently shown that haemolymph circulation during post-prandial diuresis is modulated by the synergistic activity of allatotropin (AT) and serotonin, resulting in an increase in aorta and crop contraction rates...
July 1, 2016: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/27170200/prognostic-impact-of-loop-diuretics-in-patients-with-chronic-heart-failure%C3%A3-effects-of-addition-of-renin-angiotensin-aldosterone-system-inhibitors-and-%C3%AE-blockers
#11
Masanobu Miura, Koichiro Sugimura, Yasuhiko Sakata, Satoshi Miyata, Soichiro Tadaki, Takeshi Yamauchi, Takeo Onose, Kanako Tsuji, Ruri Abe, Takuya Oikawa, Shintaro Kasahara, Kotaro Nochioka, Jun Takahashi, Hiroaki Shimokawa
BACKGROUND: It remains to be elucidated whether addition of renin-angiotensin-aldosterone system (RAAS) inhibitors and/or β-blockers to loop diuretics has a beneficial prognostic impact on chronic heart failure (CHF) patients. METHODS AND RESULTS: From the Chronic Heart failure Analysis and Registry in the Tohoku district 2 (CHART-2) Study (n=10,219), we enrolled 4,134 consecutive patients with symptomatic stage C/D CHF (mean age, 69.3 years, 67.7% male). We constructed Cox models for composite of death, myocardial infarction, stroke and HF admission...
May 25, 2016: Circulation Journal: Official Journal of the Japanese Circulation Society
https://www.readbyqxmd.com/read/27130705/a-randomized-controlled-study-of-finerenone-vs-eplerenone-in-patients-with-worsening-chronic-heart-failure-and-diabetes-mellitus-and-or-chronic-kidney-disease
#12
Gerasimos Filippatos, Stefan D Anker, Michael Böhm, Mihai Gheorghiade, Lars Køber, Henry Krum, Aldo P Maggioni, Piotr Ponikowski, Adriaan A Voors, Faiez Zannad, So-Young Kim, Christina Nowack, Giovanni Palombo, Peter Kolkhof, Nina Kimmeskamp-Kirschbaum, Alexander Pieper, Bertram Pitt
AIMS: To evaluate oral doses of the non-steroidal mineralocorticoid receptor antagonist finerenone given for 90 days in patients with worsening heart failure and reduced ejection fraction and chronic kidney disease and/or diabetes mellitus. METHODS AND RESULTS: Miner Alocorticoid Receptor antagonist Tolerability Study-Heart Failure (ARTS-HF) was a randomized, double-blind, phase 2b multicentre study (ClinicalTrials.gov: NCT01807221). Of 1286 screened patients, 1066 were randomized...
July 14, 2016: European Heart Journal
https://www.readbyqxmd.com/read/27045700/effects-of-ospemifene-on-bone-parameters-including-clinical-biomarkers-in-postmenopausal-women
#13
Ginger D Constantine, Risa Kagan, Paul D Miller
OBJECTIVE: Ospemifene is an estrogen-receptor agonist/antagonist (also known as a selective estrogen-receptor modulator) that is FDA approved for the treatment of moderate-to-severe dyspareunia, a symptom of vulvovaginal atrophy, due to menopause. Preclinical and clinical data suggest that ospemifene may also have an effect on bone health in postmenopausal women. METHODS: Relevant articles, including cellular and preclinical studies and clinical trials written in English pertaining to ospemifene and bone health, were identified from a database search of PubMed (from its inception to June 2015) and summarized in this comprehensive review...
June 2016: Menopause: the Journal of the North American Menopause Society
https://www.readbyqxmd.com/read/27027527/bazedoxifene-and-conjugated-equine-estrogen-a-combination-product-for-the-management-of-vasomotor-symptoms-and-osteoporosis-prevention-associated-with-menopause
#14
REVIEW
Elena M Umland, Lauren Karel, Nanette Santoro
Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator (SERM), has been combined with conjugated equine estrogen (CE) to create a tissue selective estrogen complex (TSEC) for the management of vasomotor symptoms (VMS) and the prevention of osteoporosis (OP) associated with menopause. Both of these outcomes of menopause contribute to significant negative effects on quality of life and increases in utilization of health care resources and dollars. Current treatment modalities for VMS and OP include estrogen therapy that requires the use of progestin in women who have a uterus to reduce the risk of endometrial hyperplasia and resultant cancer...
May 2016: Pharmacotherapy
https://www.readbyqxmd.com/read/27026433/fibroblast-growth-factor-21-restores-insulin-sensitivity-but-induces-aberrant-bone-microstructure-in-obese-insulin-resistant-rats
#15
Narattaphol Charoenphandhu, Panan Suntornsaratoon, Nateetip Krishnamra, Piangkwan Sa-Nguanmoo, Pongpun Tanajak, Xiaojie Wang, Guang Liang, Xiaokun Li, Chao Jiang, Nipon Chattipakorn, Siriporn Chattipakorn
Fibroblast growth factor (FGF)-21 is a potent endocrine factor that improves insulin resistance and obesity-associated metabolic disorders. However, concomitant activation of peroxisome proliferator-activated receptor-γ by FGF-21 makes bone susceptible to osteopenia and fragility fracture. Since an increase in body weight often induced adaptive change in bone by making it resistant to fracture, it was unclear whether FGF-21 would still induce bone defects in overweight rats. Therefore, the present study aimed to investigate bone microstructure and its mechanical properties in high fat diet (HF)-fed rats treated with 0...
March 29, 2016: Journal of Bone and Mineral Metabolism
https://www.readbyqxmd.com/read/26990682/bmpr1a-antagonist-differentially-affects-cartilage-and-bone-formation-during-fracture-healing
#16
Elise F Morgan, Jason Pittman, Anthony DeGiacomo, Daniel Cusher, Chantal Mj de Bakker, Keri A Mroszczyk, Mark W Grinstaff, Louis C Gerstenfeld
A soluble form of BMP receptor type 1A (mBMPR1A-mFC) acts as an antagonist to endogenous BMPR1A and has been shown to increase bone mass in mice. The goal of this study was to examine the effects of mBMPR1A-mFC on secondary fracture healing. Treatment consisted of 10mg/kg intraperitoneal injections of mBMPR1A-mFC twice weekly in male C57BL/6 mice. Treatment beginning at 1, 14, and 21 days post fracture assessed receptor function during endochondral bone formation, at the onset of secondary bone formation, and during coupled remodeling, respectively...
March 18, 2016: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/26989394/current-and-potential-therapeutic-strategies-for-hemodynamic-cardiorenal-syndrome
#17
REVIEW
Yoshitsugu Obi, Taehee Kim, Csaba P Kovesdy, Alpesh N Amin, Kamyar Kalantar-Zadeh
BACKGROUND: Cardiorenal syndrome (CRS) encompasses conditions in which cardiac and renal disorders co-exist and are pathophysiologically related. The newest classification of CRS into seven etiologically and clinically distinct types for direct patient management purposes includes hemodynamic, uremic, vascular, neurohumoral, anemia- and/or iron metabolism-related, mineral metabolism-related and protein-energy wasting-related CRS. This classification also emphasizes the pathophysiologic pathways...
February 2016: Cardiorenal Medicine
https://www.readbyqxmd.com/read/26875561/activation-of-strychnine-sensitive-glycine-receptors-by-shilajit-on-preoptic-hypothalamic-neurons-of-juvenile-mice
#18
Janardhan Prasad Bhattarai, Dong Hyu Cho, Seong Kyu Han
Shilajit, a mineral pitch, has been used in Ayurveda and Siddha system of medicine to treat many human ailments, and is reported to contain at least 85 minerals in ionic form. This study examined the possible mechanism of Shilajit action on preoptic hypothalamic neurons using juvenile mice. The hypothalamic neurons are the key regulator of many hormonal systems. In voltage clamp mode at a holding potential of -60 mV, and under a high chloride pipette solution, Shilajit induced dose-dependent inward current...
February 29, 2016: Chinese Journal of Physiology
https://www.readbyqxmd.com/read/26869358/effects-of-the-histamine-1-receptor-antagonist-cetirizine-on-the-osteoporotic-phenotype-in-h-k-atpase-beta-subunit-ko-mice
#19
Kristin M Aasarød, Astrid K Stunes, Mats P Mosti, Masoud Ramezanzadehkoldeh, Bjørn I Viggaklev, Janne E Reseland, Bjørn H Skallerud, Reidar Fossmark, Unni Syversen
Epidemiological studies suggest increased fracture risk in patients using proton pump inhibitors (PPIs). We have previously shown that the H(+) /K(+) ATPase beta subunit knockout (KO) mouse, which is a model of PPI-use, have lower bone mineral density (BMD) and impaired bone quality compared to wild type (WT) mice. Like PPI users, these KO mice display elevated gastric pH and hypergastrinemia, which in turn stimulates gastric histamine release. Previous studies have suggested a negative effect of histamine on bone, thus, we wanted to study whether a histamine 1 receptor (H1R) antagonist could improve bone quality in KO mice...
September 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/26827949/structural-studies-of-vitamin-d-nuclear-receptor-ligand-binding-properties
#20
Anna Y Belorusova, Natacha Rochel
The vitamin D nuclear receptor (VDR) and its natural ligand, 1α,25-dihydroxyvitamin D3 hormone (1,25(OH)2D3, or calcitriol), classically regulate mineral homeostasis and metabolism but also much broader range of biological functions, such as cell growth, differentiation, antiproliferation, apoptosis, adaptive/innate immune responses. Being widely expressed in various tissues, VDR represents an important therapeutic target in the treatment of diverse disorders. Since ligand binding is a key step in VDR-mediated signaling, numerous 1,25(OH)2D3 analogs have been synthesized in order to selectively modulate the receptor activity...
2016: Vitamins and Hormones
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