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https://www.readbyqxmd.com/read/29129760/the-key-role-of-proinflammatory-cytokines-matrix-proteins-rankl-opg-and-wnt-%C3%AE-catenin-in-bone-healing-of-hip-arthroplasty-patients
#1
Jean Cassuto, Agnetha Folestad, Jan Göthlin, Henrik Malchau, Johan Kärrholm
INTRODUCTION: We still lack understanding of why some implants fail while most remain stable after decades of use. Proinflammatory cytokines, matrix proteins and bone regulating cytokines of the RANKL/OPG (receptor activator of nuclear factor kappa B ligand/osteoprotegerin) and Wnt/β-catenin pathways are mandatory for normal bone repair but their spatial and temporal role in the healing of primary total hip arthroplasties (THA) has not been previously shown. MATERIALS AND METHODS: Twenty-four osteoarthritis patients with one-sided well-fixed primary THA were prospectively monitored during 18years (18Y) with repeated blood samples, clinical variables and radiographs...
November 9, 2017: Bone
https://www.readbyqxmd.com/read/29129406/neuropeptide-y-y2-antagonist-treated-ovariectomized-mice-exhibit-greater-bone-mineral-density
#2
K L Seldeen, P G Halley, C H Volmar, M A Rodríguez, M Hernandez, M Pang, S K Carlsson, L J Suva, C Wahlestedt, B R Troen, S P Brothers
Osteoporosis, a disease characterized by progressive bone loss and increased risk of fracture, often results from menopausal loss of estrogen in women. Neuropeptide Y has been shown to negatively regulate bone formation, with amygdala specific deletion of the Y2 receptor resulting in increased bone mass in mice. In this study, ovariectomized (OVX) mice were injected once daily with JNJ-31020028, a brain penetrant Y2 receptor small molecule antagonist to determine the effects on bone formation. Antagonist treated mice had reduced weight and showed increased whole-body bone mineral density compared to vehicle-injected mice...
November 7, 2017: Neuropeptides
https://www.readbyqxmd.com/read/29113980/management-of-endocrine-disease-novel-anabolic-treatments-for-osteoporosis
#3
Ernesto Canalis
Skeletal anabolic agents enhance bone formation, which is determined by the number and function of osteoblasts. Signals that influence the differentiation and function of cells of the osteoblast lineage play a role in the mechanism of action of anabolic agents in the skeleton. Wnts induce the differentiation of mesenchymal stem cells toward osteoblasts, and insulin-like growth factor I (IGF-I) enhances the function of mature osteoblasts. The activity of Wnt and IGF-I is controlled by proteins that bind to the growth factor or to its receptors...
November 7, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/29113523/monoclonal-antibodies-for-treating-osteoporosis
#4
Maria Felicia Faienza, Mariangela Chiarito, Gabriele D'amato, Graziana Colaianni, Silvia Colucci, Maria Grano, Giacomina Brunetti
Osteoporosis is the most widespread skeletal disease requiring innovative therapeutic strategies for its management. The understanding of receptor activator of nuclear factor kappa-B ligand (RANKL) and sclerostin's role in bone cell biology is completely changing the therapeutic landscape. RANKL supports osteoclast formation and activity and is mainly produced by cells of osteoblastic lineage. Sclerostin, an antagonist of the Wnt pathway, has a key role in bone formation and is mainly secreted by osteocytes...
November 7, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/29032198/antagonism-of-cysteinyl-leukot-riene-receptor-1-cyslt1r-by-montelukast-regulates-differentiation-of-mc3t3-e1-cells-under-overloaded-mechanical-environment
#5
Jinsong Wei, Siyuan Chen, Chengshuo Huang, Weixiong Guo, Shukai Yang, Bailin Feng, Jiaqi Chu
Long-term exposure to overloaded mechanical environment induces bone fatigue damage symptoms and osteoblast damages. Montelukast is a selective cysteinyl leukot-riene receptor 1 (cysLT1R) antagonist, which has been used for the treatment of bronchial asthma in clinics. In the current study, we have identified a novel pharmacological role of montelukast by finding that it has protective properties against overload damage in osteoblastic MC3T3-E1 cells. Firstly, our results show that CysLT1R is expressed in MC3T3-E1 cells...
October 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28742995/icaritin-induces-mc3t3-e1-subclone14-cell-differentiation-through-estrogen-receptor-mediated-erk1-2-and-p38-signaling-activation
#6
Zhidi Wu, Ling Ou, Chaopeng Wang, Li Yang, Panpan Wang, Hengrui Liu, Yingquan Xiong, Kehuan Sun, Ronghua Zhang, Xiaofeng Zhu
Icaritin (ICT), a hydrolytic product of icariin from the genus Epimedium, has many indicated pharmacological and biological activities. Several studies have shown that ICT has potential osteoprotective effects, including stimulation of osteoblast differentiation and inhibition of osteoclast differentiation. However, the molecular mechanism for this anabolic action of ICT remains largely unknown. Here, we found that ICT could enhance MC3T3-E1 subclone 14 preosteoblastic cell differentiation associated with increased mRNA levels and protein expression of the differentiation markers alkaline phosphatase (ALP), type 1 collagen (COL1), osteocalcin (OC), osteoponin (OPN) and runt-related transcription factor 2 (RUNX2), and improved mineralization, confirmed by bone nodule formation and collagen synthesis...
October 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28734986/exogenous-hedgehog-antagonist-delays-but-does-not-prevent-fracture-healing-in-young-mice
#7
Xiaochen Liu, Jennifer A McKenzie, Clayton W Maschhoff, Michael J Gardner, Matthew J Silva
Fracture healing recapitulates many aspects of developmental osteogenesis. The hedgehog (Hh) signaling pathway, essential to skeletal development, is upregulated during fracture healing, although its importance is unclear. Our goal was to assess the functional importance of Hh signaling in endochondral fracture healing. We created closed, transverse diaphyseal femur fractures in mice, stabilized with an intramedullary pin, and administered a systemic Hh inhibitor or vehicle. Because Hh pathway activation is mediated by the receptor Smoothened (Smo), we used the Smo antagonist GDC-0449 (GDC, 50mg/kg, twice daily) to target the pathway...
October 2017: Bone
https://www.readbyqxmd.com/read/28710615/aldosterone-antagonist-therapy-and-its-relationship-with-inflammation-fibrosis-thrombosis-mineral-bone-disorder-and-cardiovascular-complications-in-peritoneal-dialysis-pd-patients
#8
Rafał Donderski, Paweł Stróżecki, Beata Sulikowska, Magdalena Grajewska, Ilona Miśkowiec, Anna Stefańska, Joanna Siódmiak, Grażyna Odrowąż-Sypniewska, Jacek Manitius
BACKGROUND: High aldosterone level may contribute to pathogenesis of hypertension, vessels damage and cardiovascular system deterioration in chronic kidney disease patients. Besides its classical action via mineralocorticoid receptor, aldosterone is also involved in cell growth, inflammation, oxidative stress, endothelial dysfunction and exerts fibroproliferative effects. The aim of the study was to assess whether aldosterone antagonist treatment may influence serum level of inflammatory, fibrosis, thrombosis and mineral-bone metabolism markers in peritoneal dialysis (PD) patients and blood pressure, aortic stiffness, echocardiographic indices after 12 months of treatment...
July 14, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28696256/a-novel-subset-of-anti-inflammatory-cd138-macrophages-is-deficient-in-mice-with-experimental-lupus
#9
Shuhong Han, Haoyang Zhuang, Stepan Shumyak, Jingfan Wu, Hui Li, Li-Jun Yang, Westley H Reeves
Dead cells accumulating in the tissues may contribute to chronic inflammation. We examined the cause of impaired apoptotic cell clearance in human and murine lupus. Dead cells accumulated in bone marrow from lupus patients but not from nonautoimmune patients undergoing myeloablation, where they were efficiently removed by macrophages (MΦ). Impaired apoptotic cell uptake by MΦ also was seen in mice treated i.p. with pristane (develop lupus) but not mineral oil (MO) (do not develop lupus). The inflammatory response to both pristane and MO rapidly depleted resident (Tim4(+)) large peritoneal MΦ...
August 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28674250/prophylactic-oral-administration-of-magnesium-ameliorates-dextran-sulfate-sodium-induced-colitis-in-mice-through-a-decrease-of-colonic-accumulation-of-p2x7-receptor-expressing-mast-cells
#10
Kenshi Ohbori, Makiko Fujiwara, Akihiro Ohishi, Kentaro Nishida, Yoshinobu Uozumi, Kazuki Nagasawa
The number of patients with colitis has been increasing year by year. Recently, intestinal inflammation, as one of the factors for its onset, has been demonstrated to be induced by P2X7 receptor-mediated activation of colonic immune cells such as mast cells. Activation of P2X7 receptor (P2X7R) is known to be inhibited by divalent metal cations such as magnesium, but whether or not magnesium administration prevents/relieves colitis is unknown so far. Here, we report that oral (per os (p.o.)) administration of MgCl2 and ingestion of commercially available magnesium-rich mineral hard water relieves dextran sulfate sodium (DSS)-induced colitis in mice...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28512472/pulsed-electromagnetic-field-regulates-microrna-21-expression-to-activate-tgf-%C3%AE-signaling-in-human-bone-marrow-stromal-cells-to-enhance-osteoblast-differentiation
#11
Nagarajan Selvamurugan, Zhiming He, Daniel Rifkin, Branka Dabovic, Nicola C Partridge
Pulsed electromagnetic fields (PEMFs) have been documented to promote bone fracture healing in nonunions and increase lumbar spinal fusion rates. However, the molecular mechanisms by which PEMF stimulates differentiation of human bone marrow stromal cells (hBMSCs) into osteoblasts are not well understood. In this study the PEMF effects on hBMSCs were studied by microarray analysis. PEMF stimulation of hBMSCs' cell numbers mainly affected genes of cell cycle regulation, cell structure, and growth receptors or kinase pathways...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28506888/calcium-sensing-receptor-erk-signaling-promotes-odontoblastic-differentiation-of-human-dental-pulp-cells
#12
Hiroyuki Mizumachi, Shinichiro Yoshida, Atsushi Tomokiyo, Daigaku Hasegawa, Sayuri Hamano, Asuka Yuda, Hideki Sugii, Suguru Serita, Hiromi Mitarai, Katsuaki Koori, Naohisa Wada, Hidefumi Maeda
Activation of the G protein-coupled calcium-sensing receptor (CaSR) has crucial roles in skeletal development and bone turnover. Our recent study has identified a role for activated CaSR in the osteogenic differentiation of human periodontal ligament stem cells. Furthermore, odontoblasts residing inside the tooth pulp chamber play a central role in dentin formation. However, it remains unclear how CaSR activation affects the odontoblastic differentiation of human dental pulp cells (HDPCs). We have investigated the odontoblastic differentiation of HDPCs exposed to elevated levels of extracellular calcium (Ca) and strontium (Sr), and the contribution of CaSR and the L-type voltage-dependent calcium channel (L-VDCC) to this process...
May 12, 2017: Bone
https://www.readbyqxmd.com/read/28377982/mechanistic-insight-into-the-effects-of-aryl-hydrocarbon-receptor-activation-on-osteogenic-differentiation
#13
Chawon Yun, Joseph A Weiner, Danielle S Chun, Jonghwa Yun, Ralph W Cook, Michael S Schallmo, Abhishek S Kannan, Sean M Mitchell, Ryan D Freshman, Christian Park, Wellington K Hsu, Erin L Hsu
While inhibition of bone healing and increased rates of pseudarthrosis are known adverse outcomes associated with cigarette smoking, the underlying mechanisms by which this occurs are not well understood. Recent work has implicated the Aryl Hydrocarbon Receptor (Ahr) as one mediator of the anti-osteogenic effects of cigarette smoke (CS), which contains numerous toxic ligands for the Ahr. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin) is a high-affinity Ahr ligand frequently used to evaluate Ahr pathway activation...
June 2017: Bone Reports
https://www.readbyqxmd.com/read/28303319/effect-of-sdf-1-cxcr4-signaling-antagonist-amd3100-on-bone-mineralization-in-distraction-osteogenesis
#14
Jia Xu, Yuanfeng Chen, Yang Liu, Jinfang Zhang, Qinglin Kang, Kiwai Ho, Yimin Chai, Gang Li
Distraction osteogenesis (DO) is a widely applied technique in orthopedics surgery, which involves rapid stem cell migration, homing, and differentiation. Interactions between the chemokine receptor Cxcr4 and its ligand, stromal derived factor-1 (SDF-1), regulate hematopoietic stem cell trafficking to the ischemic area and induce their subsequent differentiation. Here, we examined SDF-1 expression and further investigated the role of SDF-1/Cxcr4 signaling antagonist AMD3100 during bone regeneration in rat DO model...
March 16, 2017: Calcified Tissue International
https://www.readbyqxmd.com/read/28287912/osteogenic-differentiation-of-mesenchymal-stromal-cells-a-comparative-analysis-between-human-subcutaneous-adipose-tissue-and-dental-pulp
#15
Iolanda D'Alimonte, Filiberto Mastrangelo, Patricia Giuliani, Laura Pierdomenico, Marco Marchisio, Mariachiara Zuccarini, Patrizia Di Iorio, Raimondo Quaresima, Francesco Caciagli, Renata Ciccarelli
White adipose tissue is a source of mesenchymal stromal/stem cells (MSCs) that are actively studied for their possible therapeutic use in bone tissue repair/remodeling. To better appreciate the osteogenic potential of these cells, we compared some properties of MSCs from human subcutaneous adipose tissue [subcutaneous-adipose stromal cells (S-ASCs)] and dental pulp stem cell (DPSCs) of third-impacted molars, the latter representing a well-established MSC source. Both undifferentiated cell types showed similar fibroblast-like morphology and mesenchymal marker expression...
June 1, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28235973/endothelin-signaling-regulates-mineralization-and-posttranscriptionally-regulates-sost-in-tmob-cells-via-mir-126-3p
#16
Michael G Johnson, Kathryn Konicke, Jasmin Kristianto, Anne Gustavson, Rachel Garbo, Xiaohu Wang, Baozhi Yuan, Robert D Blank
Previously, our laboratory identified ECE-1, encoding endothelin-converting enzyme-1 (ECE-1), as a positional candidate for a pleiotropic quantitative trait locus affecting femoral size, shape, and biomechanical performance. We hypothesized that endothelin-1 (ET-1) signaling promotes osteogenesis. Exposure of immortalized mouse osteoblast (TMOb) cells to big ET-1 increased mineralization. Following big ET-1 treatment, we measured the secretion of insulin-like-growth factor-1 (IGF1), dickkopf-homolog-1 protein 1 (DKK1), and sclerostin (SOST)...
February 2017: Physiological Reports
https://www.readbyqxmd.com/read/28228629/involvement-of-the-calcium-sensing-receptor-in-mineral-trioxide-aggregate-induced-osteogenic-gene-expression-in-murine-mc3t3-e1-cells
#17
Takuya Yasukawa, Makoto Hayashi, Natsuko Tanabe, Hiromasa Tsuda, Yusuke Suzuki, Takayuki Kawato, Naoto Suzuki, Masao Maeno, Bunnai Ogiso
Mineral trioxide aggregate (MTA) has excellent biocompatibility as well as bioactivity, including an ability to induce osteoblast differentiation. We examined the effects of the calcium-sensing receptor (CaSR) on osteogenic gene expression induced by MTA. MC3T3-E1 cells were cultured with or without (control) MTA. The expression levels of Runx2, type I collagen, and CaSR genes were analyzed by real-time polymerase chain reaction and their products were measured using enzyme-linked immunosorbent assays. The levels were increased significantly in cells exposed to MTA compared with control...
July 26, 2017: Dental Materials Journal
https://www.readbyqxmd.com/read/28132908/administration-of-an-activin-receptor-iib-ligand-trap-protects-male-juvenile-rhesus-macaques-from-simian-immunodeficiency-virus-associated-bone-loss
#18
Wen Guo, Karol M Pencina, Karyn O'Connell, Monty Montano, Liming Peng, Susan Westmoreland, Julie Glowacki, Shalender Bhasin
HIV-infected individuals are at an increased risk of osteoporosis despite effective viral suppression. Observations that myostatin null mice have increased bone mass led us to hypothesize that simian immunodeficiency virus (SIV)-associated bone loss may be attenuated by blocking myostatin/TGFβ signaling. In this proof-of-concept study, pair-housed juvenile male rhesus macaques were inoculated with SIVmac239. Four weeks later, animals were treated with vehicle or Fc-conjugated soluble activin receptor IIB (ActR2B·Fc, iv...
January 26, 2017: Bone
https://www.readbyqxmd.com/read/28091848/a-novel-combination-treatment-to-stimulate-bone-healing-and-regeneration-under-hypoxic-conditions-photobiomodulation-and-melatonin
#19
Jang-Ho Son, Bong-Soo Park, In-Ryoung Kim, Iel-Yong Sung, Yeong-Cheol Cho, Jung-Soo Kim, Yong-Deok Kim
Melatonin has anabolic effects on the bone, even under hypoxia, and laser irradiation has been shown to improve osteoblastic differentiation. The aim of this study was to investigate whether laser irradiation and melatonin would have synergistic effects on osteoblastic differentiation and mineralization under hypoxic conditions. MC3T3-E1 cells were exposed to 1% oxygen tension for the hypoxia condition. The cells were divided into four groups: G1-osteoblast differentiation medium only (as the hypoxic condition), G2-treatment with 50 μM melatonin only, G3-laser irradiation (808 nm, 80 mW, GaAlAs diode) only, and G4-treatment with 50 μM melatonin and laser irradiation (808 nm, 80 mW, GaAlAs diode)...
April 2017: Lasers in Medical Science
https://www.readbyqxmd.com/read/28030966/systemic-drugs-that-influence-titanium-implant-osseointegration
#20
REVIEW
Dragos Apostu, Ondine Lucaciu, Gheorghe Dan Osvald Lucaciu, Bogdan Crisan, Liana Crisan, Mihaela Baciut, Florin Onisor, Grigore Baciut, Radu Septimiu Câmpian, Simion Bran
Titanium implants are widely used on an increasing number of patients in orthopedic and dental medicine. Despite the good survival rates of these implants, failures that lead to important socio-economic consequences still exist. Recently, research aimed at improving implant fixation, a process called osseointegration, has focused on a new, innovative field: systemic delivery of drugs. Following implant fixation, patients receive systemic drugs that could either impair or enhance osseointegration; these drugs include anabolic and anti-catabolic bone-acting agents in addition to new treatments...
February 2017: Drug Metabolism Reviews
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