|
1
|
Sheela S, Kheder W, Samsudin ABR. Investigating the influence of titanium particle size and concentration on osteogenic response of human osteoblasts - in vitro study. Biomater Investig Dent 2024; 11:40843. [PMID: 38903775 PMCID: PMC11187976 DOI: 10.2340/biid.v11.40843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Accepted: 05/16/2024] [Indexed: 06/22/2024] Open
Abstract
Purpose The purpose of this study was to investigate the correlation between the size and concentration of titanium particles and the osteogenic response of human osteoblasts (HOB). Materials and Methods Different concentrations of titanium dioxide nano- and micro-particles were prepared and their biocompatibility on HOBs was analyzed using XTT assay. The changes in the actin cytoskeletal organization were studied by confocal laser scanning microscopy. The generation of intracellular reactive oxygen species (ROS) by HOBs after exposure to titanium dioxide particles was analyzed using ROS assay. Besides, the osteogenic potential represented by alkaline phosphatase activity, osteoprotegerin, macrophage colony stimulating factor levels, and biomineralization were analyzed. Results Short-term interaction of titanium dioxide nano- and micro-particles did not induce toxicity to HOBs. However, cells treated with 100 μg/mL titanium dioxide nano- and micro-particles demonstrated higher ROS generation compared to control. Besides, cells treated with 100 μg/mL titanium dioxide nanoparticles showed higher alkaline phosphatase activity, osteoprotegerin, macrophage colony stimulating factor levels and biomineralization compared to titanium dioxide microparticles. Conclusion Collectively, the study found titanium dioxide nanoparticles to be more biocompatible than microparticles providing an insight into the capability of nanostructures in supporting osteoblast differentiation and its plausibility in biomedical applications.
Collapse
Affiliation(s)
- Soumya Sheela
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Waad Kheder
- College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| | - A B Rani Samsudin
- College of Dental Medicine, University of Sharjah, Sharjah, United Arab Emirates
| |
Collapse
|
|
2
|
Cheng X, Tian W, Yang J, Wang J, Zhang Y. Engineering approaches to manipulate osteoclast behavior for bone regeneration. Mater Today Bio 2024; 26:101043. [PMID: 38600918 PMCID: PMC11004223 DOI: 10.1016/j.mtbio.2024.101043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 03/25/2024] [Accepted: 03/28/2024] [Indexed: 04/12/2024] Open
Abstract
Extensive research has delved into the multifaceted roles of osteoclasts beyond their traditional function in bone resorption in recent years, uncovering their significant influence on bone formation. This shift in understanding has spurred investigations into engineering strategies aimed at leveraging osteoclasts to not only inhibit bone resorption but also facilitate bone regeneration. This review seeks to comprehensively examine the mechanisms by which osteoclasts impact bone metabolism. Additionally, it explores various engineering methodologies, including the modification of bioactive material properties, localized drug delivery, and the introduction of exogenous cells, assessing their potential and mechanisms in aiding bone repair by targeting osteoclasts. Finally, the review proposes current limitations and future routes for manipulating osteoclasts through biological and material cues to facilitate bone repair.
Collapse
Affiliation(s)
- Xin Cheng
- Department of Stomatology, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, 1098 Xueyuan Road, Shenzhen 518055, Guangdong Province, China
| | - Wenzhi Tian
- Jilin University, Jilin Province Key Lab Tooth Dev & Bone Remodeling, School and Hospital of Stomatology, Department of Oral Pathology, Changchun 130041, Jilin Province, China
| | - Jianhua Yang
- Longgang District People's Hospital of Shenzhen & the Second Affiliated Hospital, The Chinese University of Hong Kong, Shenzhen 518172, Guangdong province, China
| | - Jiamian Wang
- National Innovation Center for Advanced Medical Devices, Shenzhen 518000, Guangdong Province, China
| | - Yang Zhang
- School of Dentistry, Shenzhen University Medical School, 1088 Xueyuan Road, Shenzhen 518055, Guangdong Province, China
- School of Biomedical Engineering, Shenzhen University Medical School, 1088 Xueyuan Road, Shenzhen 518055, Guangdong Province, China
| |
Collapse
|
|
3
|
Drapkina OM, Kontsevaya AV, Kalinina AM, Avdeev SN, Agaltsov MV, Alekseeva LI, Almazova II, Andreenko EY, Antipushina DN, Balanova YA, Berns SA, Budnevsky AV, Gainitdinova VV, Garanin AA, Gorbunov VM, Gorshkov AY, Grigorenko EA, Jonova BY, Drozdova LY, Druk IV, Eliashevich SO, Eliseev MS, Zharylkasynova GZ, Zabrovskaya SA, Imaeva AE, Kamilova UK, Kaprin AD, Kobalava ZD, Korsunsky DV, Kulikova OV, Kurekhyan AS, Kutishenko NP, Lavrenova EA, Lopatina MV, Lukina YV, Lukyanov MM, Lyusina EO, Mamedov MN, Mardanov BU, Mareev YV, Martsevich SY, Mitkovskaya NP, Myasnikov RP, Nebieridze DV, Orlov SA, Pereverzeva KG, Popovkina OE, Potievskaya VI, Skripnikova IA, Smirnova MI, Sooronbaev TM, Toroptsova NV, Khailova ZV, Khoronenko VE, Chashchin MG, Chernik TA, Shalnova SA, Shapovalova MM, Shepel RN, Sheptulina AF, Shishkova VN, Yuldashova RU, Yavelov IS, Yakushin SS. Comorbidity of patients with noncommunicable diseases in general practice. Eurasian guidelines. КАРДИОВАСКУЛЯРНАЯ ТЕРАПИЯ И ПРОФИЛАКТИКА 2024; 23:3696. [DOI: 10.15829/1728-8800-2024-3996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/10/2024] Open
Abstract
Создание руководства поддержано Советом по терапевтическим наукам отделения клинической медицины Российской академии наук.
Collapse
|
|
4
|
Arid J, Xavier TA, da Silva RAB, De Rossi A, da Silva LAB, de Queiroz AM, Galo R, Antunes LAA, Silva MJB, Antunes LS, Abbasoglu Z, Nelson Filho P, Küchler EC, Fukada SY. RANKL is associated with persistent primary teeth and delayed permanent tooth emergence. Int J Paediatr Dent 2019; 29:294-300. [PMID: 30656749 DOI: 10.1111/ipd.12467] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Revised: 11/13/2018] [Accepted: 01/09/2019] [Indexed: 01/08/2023]
Abstract
BACKGROUND Tooth eruption is a process that is not fully understood. AIM To evaluate whether genetic polymorphisms for RANK/RANKL/OPG are associated with delayed tooth emergence. To evaluate whether the relative expression of this genes is associated with persistent primary teeth. DESIGN To evaluate whether genetic polymorphisms for RANK/RANKL/OPG could be involved in delayed tooth emergence, saliva samples from 160 children, aged 6-13 years old, were analysed. To test if there is correlation between gene expression of RANK/RANKL/OPG in children with delayed tooth emergence and persistent primary teeth, periapical tissue from 15 children with persistent primary teeth and from 15 control subjects were collected for qPCR analysis. RESULTS Fifty-six children with delayed tooth emergence (35%) had at least one permanent tooth with delayed emergence. The T allele in RANKL (rs9594738) increased the risk of delayed tooth emergence (P = 0.02; OR = 1.71, 95%CI 1.09-2.75). The relative gene expression for RANKL and the ratio RANKL/OPG in children with delayed tooth emergence and persistent primary teeth were lower compared to controls (P = 0.02 and P = 0.005, respectively). CONCLUSIONS Data suggest that the polymorphism rs9594738 in RANKL is associated with delayed permanent tooth emergence. Moreover, reduced relative gene expression of RANKL in periapical tissue is associated with persistent primary teeth.
Collapse
Affiliation(s)
- Juliana Arid
- Department of Pediatric Dentistry, University of São Paulo - School of Dentistry of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
| | - Thaís Aparecida Xavier
- Department of Pediatric Dentistry, University of São Paulo - School of Dentistry of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
| | - Raquel Assed Bezerra da Silva
- Department of Pediatric Dentistry, University of São Paulo - School of Dentistry of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
| | - Andiara De Rossi
- Department of Pediatric Dentistry, University of São Paulo - School of Dentistry of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
| | - Lea Assed Bezerra da Silva
- Department of Pediatric Dentistry, University of São Paulo - School of Dentistry of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
| | - Alexandra Mussolino de Queiroz
- Department of Pediatric Dentistry, University of São Paulo - School of Dentistry of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
| | - Rodrigo Galo
- Department of Dentistry, Federal University of Vale do Jequitinhonha and Mucuri, Diamantina, Minas Gerais, Brazil
| | - Lívia Azeredo Alves Antunes
- Department of Specific Formation, School of Dentistry, Fluminense Federal University, Nova Friburgo, Rio de Janeiro, Brazil
| | - Marcelo José Barbosa Silva
- Laboratory of Tumor Biomarkers and Osteoimmunology, Immunology Department Institute of Biomedical Sciences, Federal University of Uberlândia, Uberlândia, Minas Gerais, Brazil
| | - Leonardo Santos Antunes
- Department of Specific Formation, School of Dentistry, Fluminense Federal University, Nova Friburgo, Rio de Janeiro, Brazil
| | - Zerrin Abbasoglu
- Department of Pediatric Dentistry, Yeditepe University, Istanbul, Turkey
| | - Paulo Nelson Filho
- Department of Pediatric Dentistry, University of São Paulo - School of Dentistry of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
| | - Erika Calvano Küchler
- Department of Pediatric Dentistry, University of São Paulo - School of Dentistry of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
| | - Sandra Yasuyo Fukada
- Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo - Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil
| |
Collapse
|
|
5
|
Faienza MF, D'Amato G, Chiarito M, Colaianni G, Colucci S, Grano M, Corbo F, Brunetti G. Mechanisms Involved in Childhood Obesity-Related Bone Fragility. Front Endocrinol (Lausanne) 2019; 10:269. [PMID: 31130918 PMCID: PMC6509993 DOI: 10.3389/fendo.2019.00269] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/02/2019] [Accepted: 04/11/2019] [Indexed: 01/11/2023] Open
Abstract
Childhood obesity is one of the major health problems in western countries. The excessive accumulation of adipose tissue causes inflammation, oxidative stress, apoptosis, and mitochondrial dysfunctions. Thus, obesity leads to the development of severe co-morbidities including type 2 diabetes mellitus, liver steatosis, cardiovascular, and neurodegenerative diseases which can develop early in life. Furthermore, obese children have low bone mineral density and a greater risk of osteoporosis and fractures. The knowledge about the interplay bone tissue and between adipose is still growing, although recent findings suggest that adipose tissue activity on bone can be fat-depot specific. Obesity is associated to a low-grade inflammation that alters the expression of adiponectin, leptin, IL-6, Monocyte Chemotactic Protein 1 (MCP1), TRAIL, LIGHT/TNFSF14, OPG, and TNFα. These molecules can affect bone metabolism, thus resulting in osteoporosis. The purpose of this review was to deepen the cellular mechanisms by which obesity may facilitate osteoporosis and bone fractures.
Collapse
Affiliation(s)
- Maria Felicia Faienza
- Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | | | - Mariangela Chiarito
- Department of Biomedical Sciences and Human Oncology, University of Bari Aldo Moro, Bari, Italy
| | - Graziana Colaianni
- Department of Emergency and Organ Transplantation, Section of Human Anatomy and Histology, University of Bari, Bari, Italy
| | - Silvia Colucci
- Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari Aldo Moro, Bari, Italy
| | - Maria Grano
- Department of Emergency and Organ Transplantation, Section of Human Anatomy and Histology, University of Bari, Bari, Italy
| | - Filomena Corbo
- Department of Pharmacy-Drug Science, University of Bari Aldo Moro, Bari, Italy
| | - Giacomina Brunetti
- Department of Basic and Medical Sciences, Neurosciences and Sense Organs, Section of Human Anatomy and Histology, University of Bari Aldo Moro, Bari, Italy
- *Correspondence: Giacomina Brunetti
| |
Collapse
|
|
6
|
Sewerin P, Le L, Vordenbäumen S, Schleich C, Sengewein R, Brinks R, Pongratz G, Bleck E, Lesch J, Mansmann U, Schneider M, Ostendorf B. Rheumatoid Arthritis Magnetic Resonance Imaging Score Predicts Therapy Response: Results of the German ArthroMark Cohort. J Rheumatol 2018; 45:753-759. [PMID: 29606664 DOI: 10.3899/jrheum.170797] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2018] [Indexed: 11/22/2022]
Abstract
OBJECTIVE Markers for treatment response in rheumatoid arthritis (RA) are lacking. The aim of the study was to assess the performance of the RA magnetic resonance imaging (MRI) scoring system (RAMRIS) in combination with serum biomarkers to predict response to methotrexate (MTX) treatment in therapy-naive patients with early RA by using high-field MRI. METHODS Twenty-eight patients with RA were prospectively assessed with baseline 3-T MRI of the clinical dominant hand, 3 and 6 months after MTX. The patients met the 2010 American College of Rheumatology/European League Against Rheumatism (EULAR) criteria [average age 56.8 yrs (range 39-74); positive for rheumatoid factor and/or anticyclic citrullinated peptide antibodies; disease duration < 6 mos (range 2-23 weeks)]. RAMRIS and serum biomarkers consisting of various experimental proteins including receptor activator of nuclear factor-κB ligand (RANKL) were obtained. Remission or treatment response was defined according to EULAR. To adjust for intrapersonal correlation, generalized linear mixed models were used. RESULTS Treatment response at 3 months was associated to low RAMRIS erosion subscores and low total RAMRIS scores (p = 0.019 and 0.03, respectively). Remission at 6 months was associated to low RANKL levels (p = 0.033). In multivariate analyses, response at 3 and 6 months was predicted more accurately with the inclusion of total RAMRIS score, RAMRIS synovitis subscore at the second metacarpophalangeal (MCP) joint, or a combination of the two (p value likelihood ratio test = 0.035, 0.035, and 0.041, respectively). Remission was more accurately predicted with inclusion of RANKL, with no significant predictive effect of MRI. CONCLUSION Baseline total RAMRIS can predict EULAR response. RAMRIS synovitis subscore at the second MCP joint and RANKL are associated with response and remission, respectively.
Collapse
Affiliation(s)
- Philipp Sewerin
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany. .,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf.
| | - Lien Le
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Stefan Vordenbäumen
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Christoph Schleich
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Ruben Sengewein
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Ralph Brinks
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Georg Pongratz
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Ellen Bleck
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Juliane Lesch
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Ulrich Mansmann
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Matthias Schneider
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| | - Benedikt Ostendorf
- From the Department and Hiller-Research-Unit for Rheumatology, and the Institute of Diagnostic and Interventional Radiology, Universitätsklinikum Düsseldorf (UKD), Heinrich-Heine-University Düsseldorf; University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology, Düsseldorf; the Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University, Munich, Germany.,P. Sewerin, MD, University Düsseldorf, Medical Faculty, Department of Endocrinology, Diabetology and Rheumatology; L. Le, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; S. Vordenbäumen, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; C. Schleich, MD, PhD, Department for Diagnostic and Interventional Radiology, UKD, Heinrich-Heine-University Düsseldorf; R. Sengewein, MD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; R. Brinks, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; G. Pongratz, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; E. Bleck, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; J. Lesch, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; U. Mansmann, PhD, Institute for Medical Information Sciences, Biometry and Epidemiology, Ludwig Maximilian University; M. Schneider, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf; B. Ostendorf, MD, PhD, Department and Hiller-Research-Unit for Rheumatology, UKD, Heinrich-Heine-University Düsseldorf
| |
Collapse
|
|
7
|
The intestinal phosphate transporter NaPi-IIb (Slc34a2) is required to protect bone during dietary phosphate restriction. Sci Rep 2017; 7:11018. [PMID: 28887454 PMCID: PMC5591270 DOI: 10.1038/s41598-017-10390-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2017] [Accepted: 08/07/2017] [Indexed: 02/04/2023] Open
Abstract
NaPi-IIb/Slc34a2 is a Na+-dependent phosphate transporter that accounts for the majority of active phosphate transport into intestinal epithelial cells. Its abundance is regulated by dietary phosphate, being high during dietary phosphate restriction. Intestinal ablation of NaPi-IIb in mice leads to increased fecal excretion of phosphate, which is compensated by enhanced renal reabsorption. Here we compared the adaptation to dietary phosphate of wild type (WT) and NaPi-IIb−/− mice. High phosphate diet (HPD) increased fecal and urinary excretion of phosphate in both groups, though NaPi-IIb−/− mice still showed lower urinary excretion than WT. In both genotypes low dietary phosphate (LDP) resulted in reduced fecal excretion and almost undetectable urinary excretion of phosphate. Consistently, the expression of renal cotransporters after prolonged LDP was similar in both groups. Plasma phosphate declined more rapidly in NaPi-IIb−/− mice upon LDP, though both genotypes had comparable levels of 1,25(OH)2vitamin D3, parathyroid hormone and fibroblast growth factor 23. Instead, NaPi-IIb−/− mice fed LDP had exacerbated hypercalciuria, higher urinary excretion of corticosterone and deoxypyridinoline, lower bone mineral density and higher number of osteoclasts. These data suggest that during dietary phosphate restriction NaPi-IIb-mediated intestinal absorption prevents excessive demineralization of bone as an alternative source of phosphate.
Collapse
|
|
8
|
Venkatesha SH, Dudics S, Astry B, Moudgil KD. Control of autoimmune inflammation by celastrol, a natural triterpenoid. Pathog Dis 2016; 74:ftw059. [PMID: 27405485 DOI: 10.1093/femspd/ftw059] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/02/2016] [Indexed: 12/19/2022] Open
Abstract
Celastrol is a bioactive compound derived from traditional Chinese medicinal herbs of the Celastraceae family. Celastrol is known to possess anti-inflammatory and anti-oxidant activities. Our studies have highlighted the immunomodulatory attributes of celastrol in adjuvant-induced arthritis (AA), an experimental model of human rheumatoid arthritis (RA). RA is an autoimmune disease characterized by chronic inflammation of the synovial lining of the joints, leading eventually to tissue damage and deformities. Identification of the molecular targets of celastrol such as the NF-κB pathway, MAPK pathway, JAK/STAT pathway and RANKL/OPG pathway has unraveled its strategic checkpoints in controlling arthritic inflammation and tissue damage in AA. The pathological events that are targeted and rectified by celastrol include increased production of pro-inflammatory cytokines; an imbalance between pathogenic T helper 17 and regulatory T cells; enhanced production of chemokines coupled with increased migration of immune cells into the joints; and increased release of mediators of osteoclastic bone damage. Accordingly, celastrol is a promising candidate for further testing in the clinic for RA therapy. Furthermore, the results of other preclinical studies suggest that celastrol might also be beneficial for the treatment of a few other autoimmune diseases besides arthritis.
Collapse
Affiliation(s)
- Shivaprasad H Venkatesha
- Department of Microbiology and Immunology, Division of Rheumatology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA
| | - Steven Dudics
- Department of Microbiology and Immunology, Division of Rheumatology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA
| | - Brian Astry
- Department of Microbiology and Immunology, Division of Rheumatology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA
| | - Kamal D Moudgil
- Department of Microbiology and Immunology, Division of Rheumatology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite 380, Baltimore, MD 21201, USA Department of Medicine, Division of Rheumatology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| |
Collapse
|
|
9
|
Kim JY, Ahn SJ, Baek JM, Yoon KH, Lee MS, Oh J. Ostericum koreanum Reduces LPS-Induced Bone Loss Through Inhibition of Osteoclastogenesis. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2016; 43:495-512. [PMID: 25967665 DOI: 10.1142/s0192415x15500317] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The roots of Ostericum koreanum (OK) Maximowicz have traditionally been used to produce an herbal medicine reported to possess anti-inflammatory, anti-oxidant, antimicrobial, and antitumor activities; however, its effect on bone metabolism has not yet been reported. The present study examined the effects of OK extract on lipopolysaccharide (LPS)-induced bone loss in mice by investigating bone structure and the levels of the receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) in serum and bone marrow fluid (BMF). The effects of OK extract on osteoclastogenesis were also investigated in mouse bone marrow macrophages by examining the formation of tartrate-resistant acid phosphatase (TRAP)-positive cells, the actin ring, and bone resorption activity. OK reduced LPS-induced bone destruction in vivo via a decrease in the RANKL/OPG ratio. Furthermore, it suppressed the formation of TRAP-positive cells and the actin ring, and reduced the bone-resorbing activity of mature osteoclasts. OK also significantly down-regulated the expression of various osteoclast-specific genes. However, it did not affect osteoblast differentiation, or the expression of genes involved in this process. These results demonstrated that OK prevented LPS-induced bone loss by decreasing the RANKL/OPG ratio in serum and BMF, and inhibited osteoclast differentiation and function, suggesting that OK represents a potential therapeutic drug for the treatment of osteoclast-associated bone diseases.
Collapse
Affiliation(s)
- Ju-Young Kim
- Imaging Science-Based Lung and Bone Diseases Research Center, Iksan, Republic of Korea
| | | | | | | | | | | |
Collapse
|
|
10
|
Esteves JC, de Souza Faloni AP, Macedo PD, Nakata PB, Chierici Marcantonio RA, Intini G, Marcantonio E. Effects on Bone Repair of Osteotomy With Drills or With Erbium, Chromium: Yttrium-Scandium-Gallium-Garnet Laser: Histomorphometric and Immunohistochemical Study. J Periodontol 2015; 87:452-60. [PMID: 26693695 DOI: 10.1902/jop.2015.150406] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
BACKGROUND The erbium, chromium:yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser has been widely used in the dental clinic; however, few studies have demonstrated the advantages of the use of this laser for bone osteotomies. The purpose of this study is to evaluate and compare the bone repair process of defects generated by the Er,Cr:YSGG laser or conventional drills. METHODS Ninety-six rats were divided into two groups of 48 animals (drill group and laser group). After surgical exposure of the right tibia, the animals were subjected to a 2-mm-diameter osteotomy created by conventional drills (drill group) or by the Er,Cr:YSGG laser (laser group). The animals were sacrificed 0, 3, 7, 14, 30, and 60 days after the creation of the defect, and histologic sections were obtained and used for histomorphometric and immunohistochemical analyses for the detection of osteocalcin, osteoprotegerin, receptor activator of nuclear factor κ-B ligand, vascular endothelial growth factor, and caspase-3. RESULTS The osteotomy with the drill produced well-delimited and smooth walls, whereas the osteotomies in the laser group were irregular and presented an amorphous basophilic line and bone necrosis that was slowly resorbed during the repair process. Despite these characteristics, bone repair was similar between groups at various time points, and, at 60 days, the defects in both groups were completely repaired by newly formed bone. CONCLUSION The repair process of osteotomies created by the Er,Cr:YSGG laser, despite producing thermal damage to bone tissue, is comparable to that with conventional drills.
Collapse
Affiliation(s)
- Jônatas Caldeira Esteves
- Department of Dental Clinic, Dental School, Federal University of Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil
| | - Ana Paula de Souza Faloni
- Department of Health Sciences, Implantology Postgraduation Course, University Center of Araraquara (UNIARA), Araraquara, São Paulo, Brazil
| | - Paula Delello Macedo
- Department of Diagnosis and Surgery, Division of Periodontology, Araraquara Dental School, Univ Estadual Paulista (UNESP), Araraquara, São Paulo, Brazil
| | - Patrícia Borges Nakata
- Department of Diagnosis and Surgery, Division of Periodontology, Araraquara Dental School, Univ Estadual Paulista (UNESP), Araraquara, São Paulo, Brazil
| | - Rosemary Adriana Chierici Marcantonio
- Department of Diagnosis and Surgery, Division of Periodontology, Araraquara Dental School, Univ Estadual Paulista (UNESP), Araraquara, São Paulo, Brazil
| | - Giuseppe Intini
- Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Harvard University, Boston, MA.,Harvard Stem Cell Institute, Cambridge, MA
| | - Elcio Marcantonio
- Department of Diagnosis and Surgery, Division of Periodontology, Araraquara Dental School, Univ Estadual Paulista (UNESP), Araraquara, São Paulo, Brazil
| |
Collapse
|
|
11
|
Balli U, Aydogdu A, Dede FO, Turer CC, Guven B. Gingival Crevicular Fluid Levels of Sclerostin, Osteoprotegerin, and Receptor Activator of Nuclear Factor-κB Ligand in Periodontitis. J Periodontol 2015; 86:1396-404. [DOI: 10.1902/jop.2015.150270] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
|
|
12
|
Shiau HJ, Aichelmann-Reidy ME, Reynolds MA. Influence of sex steroids on inflammation and bone metabolism. Periodontol 2000 2015; 64:81-94. [PMID: 24320957 DOI: 10.1111/prd.12033] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/04/2013] [Indexed: 12/16/2022]
Abstract
Sex steroids are central to sexual development and reproduction, exerting pleiotropic effects on multiple tissues and organs throughout the lifespan of humans. Sex steroids are fundamental to skeletal development, bone homeostasis and immune function. The composite effect of sex-specific genetic architecture and circulating levels of sex-steroid hormones closely parallels differences in the immune response and may account for corresponding sex-related differences in risk for chronic periodontitis, with men exhibiting greater susceptibility than women. Age-associated reductions in sex steroids also provide insight into apparent temporal increases in susceptibility to periodontitis and alveolar bone loss, particularly among women. Chronic infection and inflammatory conditions, such as periodontal disease, provide a unique platform for exploring the interface of sex steroids, immunity and bone metabolism.
Collapse
|
|
13
|
D'Amelio P, Isaia GC. Male Osteoporosis in the Elderly. Int J Endocrinol 2015; 2015:907689. [PMID: 26457082 PMCID: PMC4592737 DOI: 10.1155/2015/907689] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Accepted: 09/02/2015] [Indexed: 01/02/2023] Open
Abstract
Osteoporosis is now recognized as an important public health problem in elderly men as fragility fractures are complicated by increased morbidity, mortality, and social costs. This review comprises an overview of recent findings in pathophysiology, diagnosis, and treatment of male osteoporosis, with particular regard to the old population.
Collapse
Affiliation(s)
- Patrizia D'Amelio
- Department of Medical Science, University of Torino, 10126 Torino, Italy
| | | |
Collapse
|
|
14
|
Effects of TGF-β1 on OPG/RANKL expression of cementoblasts and osteoblasts are similar without stress but different with mechanical compressive stress. ScientificWorldJournal 2015; 2015:718180. [PMID: 25685846 PMCID: PMC4312653 DOI: 10.1155/2015/718180] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Revised: 12/06/2014] [Accepted: 12/06/2014] [Indexed: 02/05/2023] Open
Abstract
Introduction. This study aimed to explore the effects of TGF-β1 on regulating activities of cementoblasts and osteoblasts with or without stress. Material and Methods. Human recombinant TGF-β1 was added with different doses. Immunohistochemical test of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL) and Alizarin Red-S staining were conducted. Mechanical compressive stress was obtained by increasing the pressure of gaseous phase. OPG/RANKL expression was detected in both cells through quantitative real-time PCR. Results. Similar significant differences (P < 0.05) existed in OPG/RANKL change with increasing concentration of TGF-β1 without mechanical stress for cementoblasts and osteoblasts. However, under 3 h stress, OPG increased and RANKL decreased significantly (P < 0.01) but with similar OPG/RANKL change. Moreover, under 24 h stress, OPG change exhibited no difference (P > 0.05), but RANKL decreased significantly (P < 0.01) at 10 and 100 ng/mL TGF-β1 in cementoblasts. In osteoblasts, OPG increased significantly (P < 0.01) at 10 and 100 ng/mL, whereas RANKL decreased with statistical difference (P < 0.05) at 1 and 10 ng/mL. Conclusions. The effects of TGF-β1 on OPG/RANKL expression of cementoblasts and osteoblasts are similar even without mechanical stress. However, these effects are different under mechanical compressive stress.
Collapse
|
|
15
|
Jablonski H, Kauther MD, Bachmann HS, Jäger M, Wedemeyer C. Calcitonin gene-related peptide modulates the production of pro-inflammatory cytokines associated with periprosthetic osteolysis by THP-1 macrophage-like cells. Neuroimmunomodulation 2015; 22:152-65. [PMID: 24853723 DOI: 10.1159/000360988] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2013] [Accepted: 02/27/2014] [Indexed: 11/19/2022] Open
Abstract
OBJECTIVE An anti-resorptive impact of the neuropeptide calcitonin gene-related peptide (CGRP) on periprosthetic osteolysis, the leading cause of early prosthesis loosening, has been shown previously. In this study, the impact of CGRP on pro-inflammatory cytokine production associated with periprosthetic osteolysis was analysed using THP-1 macrophage-like cells. METHODS Cells were stimulated with ultra-high-molecular-weight polyethylene (UHMWPE) particles (cell-to-particle ratios of 1:100 and 1:500) and lipopolysaccharides (LPS; 1 µg/ml) to establish osteolytic conditions, and simultaneously treated with CGRP (10(-8)M). Receptor activator of nuclear factor-κB (RANK), RANK ligand (RANKL) and tumour necrosis factor (TNF)-α mRNA expression were measured by quantitative RT-PCR. RANK protein was detected by Western blot. Secreted protein levels of TNF-α as well as interleukin (IL)-1β and IL-6 were quantified in cell culture supernatants by ELISA and Bio-Plex cytokine assay, respectively. RESULTS Activation of macrophage-like cells failed to enhance the production of RANK but led to a dose- and time-dependent increase of TNF-α mRNA and secreted protein levels of TNF-α, IL-1β and IL-6. Application of CGRP time-dependently suppressed TNF-α mRNA expression induced by low-particle concentrations and LPS, while both particle- and LPS-induced secretion of TNF-α was inhibited. A pronounced inhibitory effect of CGRP on LPS-induced cytokine production at 24 h of incubation was also observed with IL-1β and IL-6. CONCLUSIONS CGRP shows a time-dependent inhibitory effect on the secretion of osteolysis-associated pro-inflammatory cytokines, indicating an indirect anti-resorptive influence of the neuropeptide on both aseptic prosthesis loosening and bacterially induced bone resorption which might enhance the life time of total joint replacements.
Collapse
Affiliation(s)
- Heidrun Jablonski
- Department of Orthopaedics, University Hospital Essen, University of Duisburg Essen, Essen, Germany
| | | | | | | | | |
Collapse
|
|
16
|
Shao J, Wang Z, Yang T, Ying H, Zhang Y, Liu S. Bone Regulates Glucose Metabolism as an Endocrine Organ through Osteocalcin. Int J Endocrinol 2015; 2015:967673. [PMID: 25873961 PMCID: PMC4383405 DOI: 10.1155/2015/967673] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2014] [Revised: 08/21/2014] [Accepted: 09/18/2014] [Indexed: 12/12/2022] Open
Abstract
Skeleton was considered as a dynamic connective tissue, which was essential for mobility, calcium homeostasis, and hematopoietic niche. However more and more evidences indicate that skeleton works not only as a structural scaffold but also as an endocrine organ, which regulates several metabolic processes. Besides osteoprotegerin (OPG), sclerostin (SOST), and Dickopf (DKK) which play essential roles in bone formation, modelling, remodelling, and homeostasis, bone can also secret hormones, such as osteocalcin (OCN), which promotes proliferation of β cells, insulin secretion, and insulin sensitivity. Additionally OCN can also regulate the fat cells and male gonad endocrine activity and be regulated by insulin and the neural system. In summary, skeleton has endocrine function via OCN and plays an important role in energy metabolism, especially in glucose metabolism.
Collapse
Affiliation(s)
- Jin Shao
- Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital/Clinical School, The Second Military Medical University, Shanghai 200135, China
| | - Zhi Wang
- Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital/Clinical School, The Second Military Medical University, Shanghai 200135, China
| | - Tieyi Yang
- Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital/Clinical School, The Second Military Medical University, Shanghai 200135, China
- *Tieyi Yang:
| | - Hui Ying
- Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital/Clinical School, The Second Military Medical University, Shanghai 200135, China
| | - Yan Zhang
- Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital/Clinical School, The Second Military Medical University, Shanghai 200135, China
| | - Shuyi Liu
- Department of Orthopaedics, Shanghai Pudong New Area Gongli Hospital/Clinical School, The Second Military Medical University, Shanghai 200135, China
| |
Collapse
|
|
17
|
Pérez de Ciriza C, Lawrie A, Varo N. Osteoprotegerin in Cardiometabolic Disorders. Int J Endocrinol 2015; 2015:564934. [PMID: 26078757 PMCID: PMC4442310 DOI: 10.1155/2015/564934] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2014] [Revised: 04/20/2015] [Accepted: 04/20/2015] [Indexed: 02/06/2023] Open
Abstract
Osteoprotegerin (OPG), a glycoprotein traditionally implicated in bone remodelling, has been recently related to cardiovascular disease (CVD). Human studies show a positive relationship between circulating OPG, vascular damage, and CVD, and as such OPG has emerged as a potential biomarker for CVD. This review focuses on the relationship between circulating OPG and different endocrine cardiometabolic alterations such as type 1 and 2 diabetes. The association of OPG with diabetic complications (neuropathy, nephropathy, or retinopathy) as well as with atherosclerosis, coronary artery calcification, morbidity, and mortality is pointed out. Moreover, OPG modulation by different treatments is also established. Besides, other associated diseases such as obesity, hypertension, and metabolic syndrome, which are known cardiovascular risk factors, are also considered.
Collapse
Affiliation(s)
- C. Pérez de Ciriza
- Department of Clinical Chemistry, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008 Pamplona, Spain
| | - A. Lawrie
- Department of Cardiovascular Science, University of Sheffield, Beech Hill Road, Sheffield S10 2RX, UK
| | - N. Varo
- Department of Clinical Chemistry, Clínica Universidad de Navarra, Avenida Pío XII 36, 31008 Pamplona, Spain
- *N. Varo:
| |
Collapse
|
|
18
|
Siddiqi MH, Siddiqi MZ, Ahn S, Kang S, Kim YJ, Sathishkumar N, Yang DU, Yang DC. Ginseng saponins and the treatment of osteoporosis: mini literature review. J Ginseng Res 2014; 37:261-8. [PMID: 24198650 PMCID: PMC3818951 DOI: 10.5142/jgr.2013.37.261] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2012] [Accepted: 12/05/2012] [Indexed: 11/18/2022] Open
Abstract
The ginseng plant (Panax ginseng Meyer) has a large number of active ingredients including steroidal saponins with a dammarane skeleton as well as protopanaxadiol and protopanaxatriol, commonly known as ginsenosides, which have antioxidant, anticancer, antidiabetic, anti-adipocyte, and sexual enhancing effects. Though several discoveries have demonstrated that ginseng saponins (ginsenosides) as the most important therapeutic agent for the treatment of osteoporosis, yet the molecular mechanism of its active metabolites is unknown. In this review, we summarize the evidence supporting the therapeutic properties of ginsenosides both in vivo and in vitro, with an emphasis on the different molecular agents comprising receptor activator of nuclear factor kappa-B ligand, receptor activator of nuclear factor kappa-B, and matrix metallopeptidase-9, as well as the bone morphogenetic protein-2 and Smad signaling pathways.
Collapse
Affiliation(s)
- Muhammad Hanif Siddiqi
- Korean Ginseng Center & Ginseng Genetic Resource Bank, Kyung Hee University, Suwon 449-701, Korea
| | | | | | | | | | | | | | | |
Collapse
|
|
19
|
Abstract
Total joint replacement surgery is being performed on an increasingly large part of the population. Clinical longevity of implants depends on their osseointegration, which is influenced by the load, the characteristics of the implant and the bone-implant interface, as well as by the quality and quantity of the surrounding bone. Aseptic loosening due to periprosthetic osteolysis is the most frequent known cause of implant failure. Wear of prosthetic materials results in the formation of numerous particles of debris that cause a complex biological response. Dual-energy X-ray Absorptiometry (DXA) is regarded as an accurate method to evaluate Bone Mineral Density (BMD) around hip or knee prostheses. Further data may be provided by a new device, the Bone Microarchitecture Analysis (BMA), which combines bone microarchitecture quantification and ultra high resolution osteo-articular imaging. Pharmacological strategies have been developed to prevent bone mass loss and to extend implant survival. Numerous trials with bisphosphonates show a protective effect on periprosthetic bone mass, up to 72 months after arthroplasty. Strontium ranelate has been demonstrated to increase the osseointegration of titanium implants in treated animals with improvement of bone microarchitecture and bone biomaterial properties.
Collapse
Affiliation(s)
- Loredana Cavalli
- Department of Surgery and Translational Medicine, University of Florence, Florence, 50139, Italy
| | - Maria Luisa Brandi
- Department of Surgery and Translational Medicine, University of Florence, Florence, 50139, Italy
| |
Collapse
|
|
20
|
Bone mass and mineral metabolism alterations in adult celiac disease: pathophysiology and clinical approach. Nutrients 2013; 5:4786-99. [PMID: 24284619 PMCID: PMC3847761 DOI: 10.3390/nu5114786] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Revised: 11/13/2013] [Accepted: 11/14/2013] [Indexed: 12/24/2022] Open
Abstract
Osteoporosis affects many patients with celiac disease (CD), representing the consequence of calcium malabsorption and persistent activation of mucosal inflammation. A slight increase of fracture risk is evident in this condition, particularly in those with overt malabsorption and in postmenopausal state. The adoption of a correct gluten-free diet (GFD) improves bone derangement, but is not able to normalize bone mass in all the patients. Biomarkers effective in the prediction of bone response to gluten-free diet are not yet available and the indications of guidelines are still imperfect and debated. In this review, the pathophysiology of bone loss is correlated to clinical aspects, defining an alternative proposal of management for this condition.
Collapse
|
|
21
|
Ota K, Quint P, Ruan M, Pederson L, Westendorf JJ, Khosla S, Oursler MJ. Sclerostin is expressed in osteoclasts from aged mice and reduces osteoclast-mediated stimulation of mineralization. J Cell Biochem 2013; 114:1901-1907. [PMID: 23494985 DOI: 10.1002/jcb.24537] [Citation(s) in RCA: 51] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2013] [Accepted: 02/27/2013] [Indexed: 12/12/2022]
Abstract
Osteoclast-mediated bone resorption precedes osteoblast-mediated bone formation through early adulthood, but formation fails to keep pace with resorption during aging. We previously identified several factors produced by osteoclasts that promote bone formation. In this study, we determined if osteoclast-produced factors contribute to the impaired bone formation with aging. We previously found that mice between the ages of 18 and 22 months develop age-related bone loss. Bone marrow-derived pre-osteoclasts were isolated from 6-week, 12-month, and 18- to 24-month-old mice and differentiated into osteoclasts in vitro. Conditioned media were collected and compared for osteoblast mineralization support. Conditioned medium from osteoclasts from all ages was able to support mineralization of bone marrow stromal cells. Concentrating the conditioned medium from 6-week-old and 12-month-old mouse marrow cells-derived osteoclasts enhanced mineralization support whereas concentrated conditioned medium from 18- to 24-month-old mouse marrow-derived osteoclasts repressed mineralization compared to base medium. This observation suggests that an inhibitor of mineralization was secreted by aged murine osteoclasts. Gene and protein analysis revealed that the Wnt antagonist sclerostin was significantly elevated in the conditioned media from 24-month-old mouse cells compared to 6-week-old mouse cells. Antibodies directed to sclerostin neutralized the influences of the aged mouse cell concentrated conditioned media on mineralization. Sclerostin is primarily produced by osteocytes in young animals. This study demonstrates that osteoclasts from aged mice also produce sclerostin in quantities that may contribute to the age-related impairment in bone formation.
Collapse
Affiliation(s)
- Kuniaki Ota
- Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905
| | - Patrick Quint
- Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905
| | - Ming Ruan
- Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905
| | - Larry Pederson
- Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905
| | - Jennifer J Westendorf
- Division of Orthopedic Research, Mayo Clinic, Rochester, MN, 55905.,Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905
| | - Sundeep Khosla
- Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905
| | - Merry Jo Oursler
- Endocrine Research Unit and Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN, 55905.,Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, 55905
| |
Collapse
|
|
22
|
Niklas A, Proff P, Gosau M, Römer P. The role of hypoxia in orthodontic tooth movement. Int J Dent 2013; 2013:841840. [PMID: 24228034 PMCID: PMC3818850 DOI: 10.1155/2013/841840] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2013] [Accepted: 09/16/2013] [Indexed: 12/12/2022] Open
Abstract
Orthodontic forces are known to have various effects on the alveolar process, such as cell deformation, inflammation, and circulatory disturbances. Each of these conditions affecting cell differentiation, cell repair, and cell migration, is driven by numerous molecular and inflammatory mediators. As a result, bone remodeling is induced, facilitating orthodontic tooth movement. However, orthodontic forces not only have cellular effects but also induce vascular changes. Orthodontic forces are known to occlude periodontal ligament vessels on the pressure side of the dental root, decreasing the blood perfusion of the tissue. This condition is accompanied by hypoxia, which is known to either affect cell proliferation or induce apoptosis, depending on the oxygen gradient. Because upregulated tissue proliferation rates are often accompanied by angiogenesis, hypoxia may be assumed to fundamentally contribute to bone remodeling processes during orthodontic treatment.
Collapse
Affiliation(s)
- A. Niklas
- Department of Orthodontics, University Medical Center Regensburg, 93053 Regensburg, Germany
| | - P. Proff
- Department of Orthodontics, University Medical Center Regensburg, 93053 Regensburg, Germany
| | - M. Gosau
- Department of Orthodontics, University Medical Center Regensburg, 93053 Regensburg, Germany
| | - P. Römer
- Department of Orthodontics, University Medical Center Regensburg, 93053 Regensburg, Germany
| |
Collapse
|
|
23
|
Giuliani N, Dalla Palma B, Bolzoni M. Bisphosphonates in Multiple Myeloma: Preclinical and Clinical Data. Clin Rev Bone Miner Metab 2013. [DOI: 10.1007/s12018-013-9143-4] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
|
|
24
|
Yoon HY, Cho YS, Jin Q, Kim HG, Woo ER, Chung YS. Effects of Ethyl Acetate Extract of Poncirus trifoliata Fruit for Glucocorticoid-Induced Osteoporosis. Biomol Ther (Seoul) 2013; 20:89-95. [PMID: 24116280 PMCID: PMC3792207 DOI: 10.4062/biomolther.2012.20.1.089] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2011] [Revised: 11/02/2011] [Accepted: 11/02/2011] [Indexed: 11/08/2022] Open
Abstract
Poncirus trifoliata fruit (PTF) affects the digestive and cardiovascular systems, and kidney function. The authors studied the effects of ethyl acetate (EtOAc) extract of PTF on the activities of osteoblasts and in an animal model. The main compounds of the EtOAc extract, naringin and poncirin have been confi rmed by HPLC and NMR analysis. Effects of osteoblastic differentiation were mea-sured by alkaline phosphatase (ALP) activity, osteopontin (OPN) protein expression and osteoprotegerin (OPG) mRNA expression in MC3T3-E1 cells. Also, osteoclast differentiation was measured by multinucleated cells (MNCs) formation through tartrate resistance acid phosphatase (TRAP)-positive staining. Bone mineral density (BMD) was measured before and after treatment with EtOAc extract of PTF in prednisolone-induced osteoporotic mice. Dexamethasone (DEX) decreased OPN and OPG expression level in MC3T3-E1 cells and ALP activity was decreased by DEX dose-dependently. EtOAc extract of PTF recovered the levels of ALP activity, and the expression of OPN and OPG in MC3T3-E1 cells treated with DEX. In osteoclast differentiation, multinucleated TRAP-positive cell formation was significantly suppressed by the EtOAc extract of PTF. Total body BMD was restored by EtOAc extract of PTF in prednisolone-induced osteoporotic mice. In conclusion, EtOAc extract of PTF recovered DEX-mediated deteriorations in osteoblastic and osteoclastic functions, and increased BMD in glucocorticoid-induced osteoporosis.
Collapse
Affiliation(s)
- Hyung-Young Yoon
- Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon 443-721
| | | | | | | | | | | |
Collapse
|
|
25
|
Msaouel P, Nandikolla G, Pneumaticos SG, Koutsilieris M. Bone microenvironment-targeted manipulations for the treatment of osteoblastic metastasis in castration-resistant prostate cancer. Expert Opin Investig Drugs 2013; 22:1385-400. [PMID: 24024652 DOI: 10.1517/13543784.2013.824422] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
INTRODUCTION Most patients with advanced prostate cancer will develop incurable bone metastasis. Although prostate cancer is the quintessential androgen-dependent neoplastic disease in males, the tumor will ultimately become refractory to androgen ablation treatment. Understanding the complex dialog between prostate cancer and the bone microenvironment has allowed the development of promising treatment strategies. AREAS COVERED The present review summarizes the pathophysiology of prostate cancer bone metastasis and provides a concise update on bone microenvironment-targeted therapies for prostate cancer. The current and future prospects and challenges of these strategies are also discussed. EXPERT OPINION A wide variety of signaling pathways, bone turnover homeostatic mechanisms and immunoregulatory networks are potential targets for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Anti-survival factor therapy can enhance the efficacy of existing treatment regimens for mCRPC by exploiting the interaction between the bone microenvironment and androgen signaling networks. In addition, many novel bone microenvironment-targeted strategies have produced promising objective clinical responses. Further elucidation of the complex interactions between prostate cancer cells and the bone stroma will open up new avenues for treatment interventions that can produce sustained cancer suppression.
Collapse
Affiliation(s)
- Pavlos Msaouel
- Jacobi Medical Center, Department of Internal Medicine, Albert Einstein College of Medicine , Bronx, NY , USA
| | | | | | | |
Collapse
|
|
26
|
Chaichanasakul T, Kang B, Bezouglaia O, Aghaloo TL, Tetradis S. Diverse osteoclastogenesis of bone marrow from mandible versus long bone. J Periodontol 2013; 85:829-36. [PMID: 24003963 DOI: 10.1902/jop.2013.130376] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Mandibles (MB) and maxillae possess unique metabolic and functional properties and demonstrate discrete responses to homeostatic, mechanical, hormonal, and developmental stimuli. Osteogenic potential of bone marrow stromal cells (BMSCs) differs between MB versus long bones (LB). Furthermore, MB- versus LB-derived osteoclasts (OCs) have disparate functional properties. This study explores the osteoclastogenic potential of rat MB versus LB marrow in vitro and in vivo under basal and stimulated conditions. METHODS Bone marrow from rat MB and LB was cultured in osteoblastic or osteoclastic differentiation media. Tartrate-resistant acid phosphatase (TRAP) staining, resorption pit assays, and real-time polymerase chain reaction were performed. Additionally, osmotic mini-pumps were implanted in animals, mandibles and tibiae were isolated, and multinucleated cells (MNCs) were measured. RESULTS MB versus LB marrow cultures that were differentiated with receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor produced more TRAP(+) MNCs and greater resorptive area. To explore MB versus LB BMSC-supported osteoclastogenesis, confluent BMSCs were cultured with parathyroid hormone (PTH), 1,25-dihydroxyvitamin D3 (1,25D3), or PTH+1,25D3. 1,25D3- or PTH+1,25D3-treated LB BMSCs expressed significantly higher RANKL and lower osteoprotegerin (OPG) mRNA and increased RANKL:OPG ratio. When whole marrow was cultured with PTH+1,25D3, more TRAP(+) MNCs were seen in LB versus MB cultures. Ultimately, rats were infused with PTH+1,25D3, and MB versus tibia MNCs were measured. Hormonal stimulation increased osteoclastogenesis in both MB and tibiae. However, higher TRAP(+) MNC numbers were observed in tibiae versus MB under basal and hormonal stimulation. CONCLUSION Collectively, these data illustrate differences of both osteoclastogenic potential and OC numbers of MB versus LB marrow.
Collapse
Affiliation(s)
- Thawinee Chaichanasakul
- Section of Pediatric Dentistry, University of California at Los Angeles School of Dentistry, Los Angeles, CA
| | | | | | | | | |
Collapse
|
|
27
|
Abstract
The transcription factor NF-κB is a family of proteins involved in signaling pathways essential for normal cellular functions and development. Deletion of various components of this pathway resulted with abnormal skeletal development. Research in the last decade has established that NF-κB signaling mediates RANK ligand-induced osteoclastogenesis. Consistently, it was shown that inhibition of NF-κB was an effective approach to inhibit osteoclast formation and bone resorptive activity. Identification of the molecular machinery underlying NF-κB activation permitted osteoclast-specific deletion of the major components of this pathway. As a result, it was clear that deletion of members of the proximal IKK kinase complex and the distal NF-κB subunits and downstream regulators affected skeletal development. These studies provided several targets of therapeutic intervention in osteolytic diseases. NF-κB activity has been also described as the centerpiece of inflammatory responses and is considered a potent mediator of inflammatory osteolysis. Indeed, inflammatory insults exacerbate physiologic RANKL-induced NF-κB signals leading to exaggerated responses and to inflammatory osteolysis. These superimposed NF-κB activities appear to underlie several bone pathologies. This review will describe the individual roles of NF-κB molecules in bone resorption and inflammatory osteolysis.
Collapse
Affiliation(s)
- Y Abu-Amer
- Department of Orthopedic Surgery, Department of Cell Biology & Physiology, Washington University School of Medicine, 660S. Euclid Avenue, Saint Louis, MO 63110, USA.
| |
Collapse
|
|
28
|
Enhos S, Veli I, Cakmak O, Ucar FI, Alkan A, Uysal T. OPG and RANKL levels around miniscrew implants during orthodontic tooth movement. Am J Orthod Dentofacial Orthop 2013; 144:203-9. [PMID: 23910201 DOI: 10.1016/j.ajodo.2013.02.028] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2012] [Revised: 02/01/2013] [Accepted: 02/01/2013] [Indexed: 11/26/2022]
Abstract
INTRODUCTION The aim of this study was to determine the peri-miniscrew implant crevicular fluid receptor activator of nuclear factor-кB ligand (RANKL) and osteoprotegerin (OPG) levels around loaded and unloaded miniscrew implants at different time intervals. METHODS Twenty loaded and 16 unloaded miniscrew implants were included in this study. All miniscrew implants were placed bilaterally between the maxillary second premolars and first molars as anchorage units for canine distalization. Peri-miniscrew implant crevicular fluid was taken from the mesiobuccal aspects of the loaded and unloaded miniscrew implants before loading; at 24, 48, and 168 hours; and on day 30 after force application. Enzyme-linked immunosorbent assay kits were used to determine RANKL and OPG levels in the peri-miniscrew implant crevicular fluid samples. Wilcoxon, Mann-Whitney U, and Spearman correlation tests were used for statistical evaluations at the P <0.05 level. RESULTS Although the total amount of OPG was not different between the groups, the total amount of RANKL was significantly elevated in the loaded miniscrew implant group (P <0.05) at all time periods. Peri-miniscrew implant crevicular fluid volume was the highest at 48 hours in the loaded group. Also, the OPG/RANKL ratio in the peri-miniscrew implant crevicular fluid was significantly decreased in the loaded miniscrew implant group. CONCLUSIONS The OPG and RANKL levels vary around loaded and unloaded miniscrew implants as a result of force application.
Collapse
Affiliation(s)
- Sukru Enhos
- Department of Periodontology, Faculty of Dentistry, Izmir Katip Celebi University, Izmir, Turkey
| | | | | | | | | | | |
Collapse
|
|
29
|
Guner I, Uzun DD, Yaman MO, Genc H, Gelisgen R, Korkmaz GG, Hallac M, Yelmen N, Sahin G, Karter Y, Simsek G. The effect of chronic long-term intermittent hypobaric hypoxia on bone mineral density in rats: role of nitric oxide. Biol Trace Elem Res 2013; 154:262-7. [PMID: 23771686 DOI: 10.1007/s12011-013-9722-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2013] [Accepted: 05/30/2013] [Indexed: 12/18/2022]
Abstract
Intermittent hypoxia is the most common pattern of hypoxic exposure in humans. The effect of chronic long-term intermittent hypobaric hypoxia (CLTIHH) on bone metabolism is not investigated. We examined the effect of CLTIHH on bone metabolism and the role of nitric oxide (NO) in this process. The rats were divided into three groups in this study. The animals in groups I and II have been exposed to CLTIHH. The animals in group II were also treated with nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester. To obtain CLTIHH, rats were placed in a hypobaric chamber (430 mm Hg; 5 h/day, 5 days/week, 5 weeks). The group III (control) rats breathed room air in the same environment. At the begining of the experiments, bone mineral density (BMD) of the animals were measured, and blood samples were collected from the tail vein. After the 5-week CLTIHH period, the same measurements were repeated. Parathyroid hormone, calcium, phosphate, bone alkaline phosphatase (b-ALP), NO, interleukin 1 beta, interleukin 6, and tumor necrosis factor alpha levels were determined. The cytokines, NO levels, and BMD in CLTIHH-induced rats were higher compared with baseline and control values. The cytokines, b-ALP, and BMD increased while NO levels decreased in the group II compared with baseline values. BMD values of group II were lower than group I but higher than control group. Our results suggested that CLTIHH has positive effects on bone density. Intermittent hypoxia protocols may be developed for treatment and prevention of osteopenia and osteoporosis.
Collapse
Affiliation(s)
- Ibrahim Guner
- Department of Physiology, Cerrahpasa Faculty of Medicine, Istanbul University, Fatih, Istanbul, Turkey
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
30
|
Zhang PF, Pan L, Luo ZY, Zhao HJ, Cai SX. Interrelationship of circulating matrix metalloproteinase-9, TNF-α, and OPG/RANK/RANKL systems in COPD patients with osteoporosis. COPD 2013; 10:650-6. [PMID: 23845033 DOI: 10.3109/15412555.2013.813928] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Previous studies have shown that matrix metalloproteinase-9 (MMP-9) and its cognate inhibitor TIMP-1, inflammatory cytokine TNF-α, and the OPG/RANK/RANKL system may each play individual roles in the pathogenesis of osteoporosis in patients with COPD. In the present study, we investigated the interrelationships of these factors in male COPD patients with and without osteoporosis. The serum levels of MMP-9, MMP-9/TIMP-1 ratio, TNF-α, RANKL, OPG, and the RANKL/OPG ratio were higher in COPD patients with osteoporosis than in individuals with normal or low bone mineral density (BMD) (N = 30, all P < 0.05 or < 0.01). The lung function FEV1%Pre and the BMD of the lumbar spine and femoral neck were found to be negatively correlated with MMP-9 serum level (r = -0.36, P < 0.05, r = -0.58, P < 0.001, and r = -0.62, P < 0.01, respectively), RANKL serum level (r = -0.21, P < 0.05, and r = -0.25, P < 0.05, and r = -0.26, P < 0.05, respectively), and RANKL/OPG ratio (r = -0.23, P < 0.05, r = -0.33, P < 0.05, and r = -0.38, P < 0.05, respectively). However, they had no correlation with TIMP-1, TNF-α, OPG, or RANK. The MMP-9 serum level was found to be positively correlated with TNF-α level (r = 0.35, P < 0.05) and RANKL/OPG ratio (r = 0.27, P < 0.05) but not associated with RANKL. These results suggest that MMP-9, TNF-α, and the OPG/RANK/RANKL system may be closely interrelated and may play interactive roles in pathogenesis of osteoporosis in COPD.
Collapse
Affiliation(s)
- Pei-fang Zhang
- 1Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University , Guangzhou 510515 , China
| | | | | | | | | |
Collapse
|
|
31
|
Anghel R, Bachmann A, Bekşac M, Brodowicz T, Finek J, Komadina R, Krzemieniecki K, Lang I, Marencak J, von Moos R, Pecherstorfer M, Rordorf T, Vrbanec D, Zielinski C. Expert opinion 2011 on the use of new anti-resorptive agents in the prevention of skeletal-related events in metastatic bone disease. Wien Klin Wochenschr 2013; 125:439-47. [PMID: 23832237 DOI: 10.1007/s00508-013-0385-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2012] [Accepted: 05/23/2013] [Indexed: 02/02/2023]
Abstract
Bisphosphonates have been a mainstay in the treatment of cancer-related bone disease and have greatly reduced the risk of skeletal complications. More recently, clinical studies suggested additional benefits of denosumab over zoledronic acid in the prevention of skeletal related events. Similar adverse event profiles have been reported for bisphosphonates and denosumab, with infrequent occurrences of osteonecrosis of the jaw with both agents, higher incidence of renal deterioration with zoledronic acid, and higher incidence of hypocalcaemia with denosumab. Based on current evidence, the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines do not recommend one drug class over the other in patients with metastatic bone disease. Denosumab, however, may present advantages over bisphosphonates in patients suffering from chronic renal insufficiency. Further research and growing clinical experience will refine the evidence based on which decisions in daily clinical practice can be taken.
Collapse
|
|
32
|
Mozzanega B, Gizzo S, Bernardi D, Salmaso L, Patrelli TS, Mioni R, Finos L, Nardelli GB. Cyclic variations of bone resorption mediators and markers in the different phases of the menstrual cycle. J Bone Miner Metab 2013; 31:461-7. [PMID: 23479185 DOI: 10.1007/s00774-013-0430-4] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2012] [Accepted: 01/24/2013] [Indexed: 11/29/2022]
Abstract
Female hormones are very important in regulating bone homeostasis; the drop of estrogen levels occurring at menopause is linked to a dramatic prevalence of bone resorption on formation. Only a small number of studies investigated the relationship between changes in circulating female sex hormones and the markers and mediators of bone homeostasis and they showed conflicting results. To explore such relationships we studied 20 young fertile healthy women, aged between 19 and 32 years. None had received hormone treatment for at least 6 months. We assayed luteinizing hormone, follicle-stimulating hormone, progesterone and 17β-estradiol, as well as the levels of osteoprotegerin (OPG), C-terminal telopeptide of collagen type I (CTx) and RANKL (receptor activator of nuclear factor-B ligand) in samples drawn from every subject at four different times during the menstrual cycle when estrogens are lowest, at the start of the cycle: T 0 (2-4th day); when estrogens are highest, in the pre-ovulatory period: T 14 (12-14th day); when progesterone activity is highest, in the advanced luteal phase: T 26 (24-26th day); and again at the start of the next cycle: T 01 (2-4th day). We observed that CTx levels are highest at the start of the cycle, decreased significantly from T 0 to T 26 (pfwe = 0.0455) and then increased from T 26 to T 01 (pfwe = 0.0415); OPG, on the other hand, which was also highest at the start of the cycle, decreased significantly from T 0 to T 14 (pfwe = 0.02) and then increased, though not significantly, from T 14 to T 01; no variation was observed in RANKL values at any time. We observed inverse correlations between estradiol and OPG levels, which became highly significant at T 01 between estradiol nadir and OPG peak levels (pfw = 0.0095). Furthermore, the increase of estradiol from T 0 to T 14 was negatively correlated with the concomitant decrease of OPG (pfwe = 0.0277), as was the fall of estradiol from T 26 to T 01 with the OPG peak levels, both at T 01 (pfw = 0.0045) and at T 0 (pfwe = 0.0381). We also observed direct correlations between the OPG levels and the variations of progesterone in the preceding intervals, but they never attained statistical significance. We conclude that OPG and CTx fluctuation during the menstrual cycle are likely due to the physiological variations of sex steroids levels.
Collapse
Affiliation(s)
- Bruno Mozzanega
- Dipartimento della Salute della Donna del Bambino, U.O.C. di Clinica Ginecologica e Ostetrica, Via Giustiniani 3, 35128, Padua, Italy
| | | | | | | | | | | | | | | |
Collapse
|
|
33
|
Smad3 is the key to transforming growth factor-β1-induced osteoclast differentiation in giant cell tumor of bone. Med Oncol 2013; 30:606. [DOI: 10.1007/s12032-013-0606-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2013] [Accepted: 05/09/2013] [Indexed: 01/29/2023]
|
|
34
|
Luo J, Wen H, Guo H, Cai Q, Li S, Li X. 1,25-dihydroxyvitamin D3 inhibits the RANKL pathway and impacts on the production of pathway-associated cytokines in early rheumatoid arthritis. BIOMED RESEARCH INTERNATIONAL 2013; 2013:101805. [PMID: 23710436 PMCID: PMC3654697 DOI: 10.1155/2013/101805] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/28/2013] [Revised: 04/01/2013] [Accepted: 04/03/2013] [Indexed: 01/16/2023]
Abstract
OBJECTIVES To study effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on RANKL signaling pathway and pathway-associated cytokines in patients with rheumatoid arthritis (RA). METHODS Receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), IFN- γ , IL-6, TNF- α , IL-17, and IL-4 were examined in 54 patients with incipient RA using a cytometric bead array (CBA) or an enzyme-linked immunosorbent assay (ELISA). RESULTS After 72 hours of incubation of peripheral blood mononuclear cells (PBMCs) with 1,25(OH)2D3 in RA patients, the levels of RANKL, TNF- α , IL-17 and IL-6 significantly decreased compared to those of the control. 1,25(OH)2D3 had no significantly impact on the levels of OPG, RANKL/OPG, and IL-4. CONCLUSIONS The present study demonstrated that 1,25(OH)2D3 reduced the production of RANKL and the secretion of TNF- α , IL-17, and IL-6 in PBMCs of RA patients, which indicated that 1,25(OH)2D3 might be able to decrease damage of cartilage and bone in RA patients by regulating the expression of RANKL signaling pathway and pathway-associated cytokines.
Collapse
Affiliation(s)
- Jing Luo
- Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Hongyan Wen
- Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Hui Guo
- Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| | - Qi Cai
- Arizona Health Sciences Center, 1501 N. Campbell, Room 4104, P.O. Box 245051, Tucson, AZ 85724, USA
| | - Shuangtian Li
- University of Washington, 1410 NE Campus Parkway, 459 Schmitz Hall, P.O. Box 355832, Seattle, WA 98195-5832, USA
| | - Xiaofeng Li
- Division of Rheumatology, Department of Medicine, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, China
| |
Collapse
|
|
35
|
Moon HJ, Ko WK, Jung MS, Kim JH, Lee WJ, Park KS, Heo JK, Bang JB, Kwon IK. Coenzyme Q10 Regulates Osteoclast and Osteoblast Differentiation. J Food Sci 2013; 78:H785-891. [DOI: 10.1111/1750-3841.12116] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Accepted: 02/17/2013] [Indexed: 01/28/2023]
Affiliation(s)
- Ho-Jin Moon
- Dept. of Maxillofacial Biomedical Engineering and Inst. of Oral Biology; School of Dentistry; Kyung Hee Univ.; Seoul 130-701; Republic of Korea
| | - Wan-Kyu Ko
- Dept. of Maxillofacial Biomedical Engineering and Inst. of Oral Biology; School of Dentistry; Kyung Hee Univ.; Seoul 130-701; Republic of Korea
| | - Min-Seo Jung
- Dept. of Maxillofacial Biomedical Engineering and Inst. of Oral Biology; School of Dentistry; Kyung Hee Univ.; Seoul 130-701; Republic of Korea
| | - Jung Ho Kim
- Dept. of Maxillofacial Biomedical Engineering and Inst. of Oral Biology; School of Dentistry; Kyung Hee Univ.; Seoul 130-701; Republic of Korea
| | - Won-Jun Lee
- Dept. of Chemical and Biomolecular Engineering; Interdisciplinary Program of Integrated Biotechnology; Sogang Univ.; Seoul 121-742; Republic of Korea
| | - Kyoung-Sun Park
- Dept. of Oriental Gynecology; College of Oriental Medicine; Kyung Hee Univ.; Seoul 130-701; Republic of Korea
| | - Ja-Kyung Heo
- Dept. of Oriental Gynecology; College of Oriental Medicine; Kyung Hee Univ.; Seoul 130-701; Republic of Korea
| | - Jae Beum Bang
- Dept. of Dental Education; School of Dentistry; Kyung Hee Univ.; Seoul 130-701; Republic of Korea
| | - Il Keun Kwon
- Dept. of Maxillofacial Biomedical Engineering and Inst. of Oral Biology; School of Dentistry; Kyung Hee Univ.; Seoul 130-701; Republic of Korea
| |
Collapse
|
|
36
|
Balani D, Aeberli D, Hofstetter W, Seitz M. Interleukin-17A stimulates granulocyte-macrophage colony-stimulating factor release by murine osteoblasts in the presence of 1,25-dihydroxyvitamin D(3) and inhibits murine osteoclast development in vitro. ACTA ACUST UNITED AC 2013; 65:436-46. [PMID: 23124514 DOI: 10.1002/art.37762] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2012] [Accepted: 10/16/2012] [Indexed: 11/11/2022]
Abstract
OBJECTIVE To investigate the effects of interleukin-17A (IL-17A) on osteoclastogenesis in vitro. METHODS Bone marrow cells (BMCs) were isolated from the excised tibia and femora of wild-type C57BL/6J mice, and osteoblasts were obtained by sequential digestion of the calvariae of ddY, C57BL/6J, and granulocyte-macrophage colony-stimulating factor-knockout (GM-CSF(-/-)) mice. Monocultures of BMCs or cocultures of BMCs and osteoblasts were supplemented with or without 1,25-dihydroxyvitamin D(3)(1,25[OH](2)D(3)), recombinant human macrophage colony-stimulating factor (M-CSF), RANKL, and IL-17A. After 5-6 days, the cultures were fixed with 4% paraformaldehyde and subsequently stained for the osteoclast marker enzyme tartrate-resistant acid phosphatase (TRAP). Osteoprotegerin (OPG) and GM-CSF expression were measured by enzyme-linked immunosorbent assay, and transcripts for RANK and RANKL were detected by real-time polymerase chain reaction. RESULTS In both culture systems, IL-17A alone did not affect the development of osteoclasts. However, the addition of IL-17A plus 1,25(OH)(2)D(3) to cocultures inhibited early osteoclast development within the first 3 days of culture and induced release of GM-CSF into the culture supernatants. Furthermore, in cocultures of GM-CSF(-/-) mouse osteoblasts and wild-type mouse BMCs, IL-17A did not affect osteoclast development, corroborating the role of GM-CSF as the mediator of the observed inhibition of osteoclastogenesis by IL-17A. CONCLUSION These findings suggest that IL-17A interferes with the differentiation of osteoclast precursors by inducing the release of GM-CSF from osteoblasts.
Collapse
Affiliation(s)
- Deepak Balani
- Bern University Hospital and University of Bern, Bern, Switzerland
| | | | | | | |
Collapse
|
|
37
|
Kim EJ, Bu SY, Sung MK, Choi MK. Effects of silicon on osteoblast activity and bone mineralization of MC3T3-E1 cells. Biol Trace Elem Res 2013; 152:105-12. [PMID: 23306944 DOI: 10.1007/s12011-012-9593-4] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2012] [Accepted: 12/22/2012] [Indexed: 10/27/2022]
Abstract
Previous studies have reported that dietary silicon (Si) intake is positively associated with bone health including bone mineral density. Although the amount of Si intake is high among trace elements in humans, how dietary Si affects bone formation at the cellular level is not well addressed. The purpose of this study was to investigate the role of Si in osteoblast activity and bone mineralization. MC3T3-E1 was cultured as mature osteoblasts and treated with sodium metasilicate (0, 1, 5, 10, 25, 50, and 100 μM) as a source of Si. After 7 days of treatment, 5 and 10 μM of sodium metasilicate significantly increased intracellular alkaline phosphatase activity (p < 0.05) when compared to the control. Additionally, all doses of sodium metasilicate (1, 5, 10, 25, 50, and 100 μM) increased mineralized nodule formation at 14 days of differentiation as evidenced by increased Alizarin Red S staining. In the analysis of gene expression, 50 μM of sodium metasilicate upregulated type I collagen (COL-I) compared to the control group. However, the increase of COL-I gene expression as a result of treatment with 1, 10, 25, and 100 μM of sodium metasilicate did not reach statistical significance. mRNA expression of insulin-like growth factor-I and receptor activator of NF-κB ligand was not significantly changed at any dose of sodium metasilicate (0, 1, 5, 10, 25, 50, and 100 μM). In light of the results, we conclude that Si has a positive effect on bone metabolism by enhancing osteoblast mineralization activity.
Collapse
Affiliation(s)
- Eun-Jin Kim
- Division of Food Science, Kongju National University, Yesan 340-702, South Korea
| | | | | | | |
Collapse
|
|
38
|
Morse LR, Sudhakar S, Lazzari AA, Tun C, Garshick E, Zafonte R, Battaglino RA. Sclerostin: a candidate biomarker of SCI-induced osteoporosis. Osteoporos Int 2013; 24:961-8. [PMID: 22801952 PMCID: PMC3611240 DOI: 10.1007/s00198-012-2072-0] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2012] [Accepted: 05/25/2012] [Indexed: 12/17/2022]
Abstract
UNLABELLED We assessed several circulating proteins as candidate biomarkers of bone status in men with chronic spinal cord injury. We report that sclerostin is significantly associated with bone mineral content and bone density at all skeletal sites tested. We found no association between bone and any other tested biomarker. INTRODUCTION Spinal cord injury results in severe osteoporosis. To date, no circulating biomarker of spinal cord injury (SCI)-induced osteoporosis has been identified. We recently reported that circulating sclerostin is associated with bone density in chronic SCI. In this study, we assessed several circulating proteins as candidate biomarkers of bone in men with chronic SCI. METHODS We assessed the relationship between bone mineral content or bone density and the following circulating bone-related proteins: sclerostin, DKK-1, soluble receptor activator of nuclear factor kappa B ligand, osteoprotegerin, osteocalcin, and c-telopeptide in 39 men with chronic SCI and 10 men with no SCI. RESULTS After adjusting for age, lower sclerostin levels were significantly associated with lower bone mineral content and bone density at all skeletal sites tested (p = 0.0002-0.03). No other circulating protein was associated with bone mineral content or bone mineral density (p = 0.18-0.99). CONCLUSION These findings suggest that circulating sclerostin reflects the severity of bone loss and is a candidate biomarker of osteoporosis severity in chronic SCI.
Collapse
Affiliation(s)
- L. R. Morse
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA. Spaulding-Harvard SCI Model System, Spaulding Rehabilitation Hospital, Boston, MA, USA. The Forsyth Institute, Cambridge, MA, USA. Spinal Cord Injury Service, VA Boston Healthcare System, Boston, MA, USA
| | - S. Sudhakar
- Spaulding-Harvard SCI Model System, Spaulding Rehabilitation Hospital, Boston, MA, USA
| | - A. A. Lazzari
- Primary Care and Rehabilitation Sections, VA Boston Healthcare System and Boston University School of Medicine, Boston, MA, USA
| | - C. Tun
- Rehabilitation Medicine Service, VA Boston Healthcare System, Boston, MA, USA
| | - E. Garshick
- Pulmonary and Critical Care Medicine Section, Medical Service, VA Boston Healthcare System, Boston, MA, USA. Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
| | - R. Zafonte
- Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA. Spaulding-Harvard SCI Model System, Spaulding Rehabilitation Hospital, Boston, MA, USA
| | - R. A. Battaglino
- The Forsyth Institute, Cambridge, MA, USA. Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, USA. Skeletal Biology Department, The Forsyth Institute, 245 First St., Cambridge, MA 02142, USA
| |
Collapse
|
|
39
|
Su N, Chen M, Chen S, Li C, Xie Y, Zhu Y, Zhang Y, Zhao L, He Q, Du X, Chen D, Chen L. Overexpression of H1 calponin in osteoblast lineage cells leads to a decrease in bone mass by disrupting osteoblast function and promoting osteoclast formation. J Bone Miner Res 2013; 28:660-71. [PMID: 23044709 PMCID: PMC3716280 DOI: 10.1002/jbmr.1778] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2012] [Revised: 08/24/2012] [Accepted: 09/07/2012] [Indexed: 02/03/2023]
Abstract
H1 calponin (CNN1) is known as a smooth muscle-specific, actin-binding protein which regulates smooth muscle contractive activity. Although previous studies have shown that CNN1 has effect on bone, the mechanism is not well defined. To investigate the role of CNN1 in maintaining bone homeostasis, we generated transgenic mice overexpressing Cnn1 under the control of the osteoblast-specific 3.6-kb Col1a1 promoter. Col1a1-Cnn1 transgenic mice showed delayed bone formation at embryonic stage and decreased bone mass at adult stage. Morphology analyses showed reduced trabecular number, thickness and defects in bone formation. The proliferation and migration of osteoblasts were decreased in Col1a1-Cnn1 mice due to alterations in cytoskeleton. The early osteoblast differentiation of Col1a1-Cnn1 mice was increased, but the late stage differentiation and mineralization of osteoblasts derived from Col1a1-Cnn1 mice were significantly decreased. In addition to impaired bone formation, the decreased bone mass was also associated with enhanced osteoclastogenesis. Tartrate-resistant acid phosphatase (TRAP) staining revealed increased osteoclast numbers in tibias of 2-month-old Col1a1-Cnn1 mice, and increased numbers of osteoclasts co-cultured with Col1a1-Cnn1 osteoblasts. The ratio of RANKL to OPG was significantly increased in Col1a1-Cnn1 osteoblasts. These findings reveal a novel function of CNN1 in maintaining bone homeostasis by coupling bone formation to bone resorption.
Collapse
Affiliation(s)
- Nan Su
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Maomao Chen
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Siyu Chen
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Can Li
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Yangli Xie
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Ying Zhu
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Yaozong Zhang
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Ling Zhao
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Qifen He
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Xiaolan Du
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| | - Di Chen
- Department of Biochemistry, Rush University Medical Center, Chicago, IL, USA
| | - Lin Chen
- Center of Bone Metabolism and Repair, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China
| |
Collapse
|
|
40
|
Mazurkiewicz T, Matuszewski L, Matuszewska A, Jaszek M. Implanted bisphosphonates in bone cement affect bone markers in rat serum. INTERNATIONAL ORTHOPAEDICS 2013; 37:969-74. [PMID: 23404413 PMCID: PMC3631498 DOI: 10.1007/s00264-013-1816-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/07/2012] [Accepted: 01/26/2013] [Indexed: 01/06/2023]
Abstract
PURPOSE Bisphosphonates (BPs) are antiresorptive drugs that provide important effects on bone turnover. The key to the high efficiency of BPs is their affinity for bone tissue, and their chemical structure provides their molecular mechanism of action. BPs are widely used to treat a variety of diseases that cause excess bone resorption, such as bone metastasis, hypercalcaemia due to malignancy and Paget's disease. The goal of this study was to assess whether the bisphosphonate (Pamifos®) present in bone cement has any effect on bone turnover. In this paper, we present changes in cytokine levels in the serum of rats treated surgically. METHODS Research was performed on 40 adult male Wistar rats. The rats were divided into four groups: two control groups (A, B) and two experimental groups (C, D). Bone in rats in the experimental groups was implanted with BP-enriched cement, whereas bone in control-groups rats was implanted with clean cement (without BPs). RESULTS We found a higher concentration of tumour necrosis factor alpha (TNF-α) three weeks after surgery in rats implanted with BP-enriched cement compared with rats implanted with clean cement. After six weeks of treatment, TNF-α levels decreased significantly in rats treated with BP-enriched cement, whereas the control group experienced an increase in TNF-α. The concentration of osteoprotegerin ligand (OPG) was higher in rats with BP implants. We found high levels of receptor activator of nuclear factor kappa-B ligand (RANKL) in rats after implantation of cement without BP in both groups. CONCLUSIONS We conclude that use of bisphosphonate (Pamifos®), which is present in bone cement, has an effect on bone turnover in that BPs stimulate an increase in OPG and a decrease in RANKL in the bone microenvironment and thus may be an important component of mechanisms that reduce bone resorption. Therefore, the use of BP-enriched cement implants appears to be justified.
Collapse
Affiliation(s)
- Tomasz Mazurkiewicz
- Orthopedic and Traumatology Department, Medical University of Lublin, Lublin, Poland
| | | | | | | |
Collapse
|
|
41
|
Mediators of inflammation-induced bone damage in arthritis and their control by herbal products. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:518094. [PMID: 23476694 PMCID: PMC3582100 DOI: 10.1155/2013/518094] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/09/2012] [Revised: 12/06/2012] [Accepted: 12/10/2012] [Indexed: 12/17/2022]
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints leading to bone and cartilage damage. Untreated inflammatory arthritis can result in severe deformities and disability. The use of anti-inflammatory agents and biologics has been the mainstay of treatment of RA. However, the prolonged use of such agents may lead to severe adverse reactions. In addition, many of these drugs are quite expensive. These limitations have necessitated the search for newer therapeutic agents for RA. Natural plant products offer a promising resource for potential antiarthritic agents. We describe here the cellular and soluble mediators of inflammation-induced bone damage (osteoimmunology) in arthritis. We also elaborate upon various herbal products that possess antiarthritic activity, particularly mentioning the specific target molecules. As the use of natural product supplements by RA patients is increasing, this paper presents timely and useful information about the mechanism of action of promising herbal products that can inhibit the progression of inflammation and bone damage in the course of arthritis.
Collapse
|
|
42
|
Weitzmann MN. The Role of Inflammatory Cytokines, the RANKL/OPG Axis, and the Immunoskeletal Interface in Physiological Bone Turnover and Osteoporosis. SCIENTIFICA 2013; 2013:125705. [PMID: 24278766 PMCID: PMC3820310 DOI: 10.1155/2013/125705] [Citation(s) in RCA: 138] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/06/2012] [Accepted: 12/24/2012] [Indexed: 05/30/2023]
Abstract
Although it has long been recognized that inflammation, a consequence of immune-driven processes, significantly impacts bone turnover, the degree of centralization of skeletal and immune functions has begun to be dissected only recently. It is now recognized that formation of osteoclasts, the bone resorbing cells of the body, is centered on the key osteoclastogenic cytokine, receptor activator of NF- κ B ligand (RANKL). Although numerous inflammatory cytokines are now recognized to promote osteoclast formation and skeletal degradation, with just a few exceptions, RANKL is now considered to be the final downstream effector cytokine that drives osteoclastogenesis and regulates osteoclastic bone resorption. The biological activity of RANKL is moderated by its physiological decoy receptor, osteoprotegerin (OPG). New discoveries concerning the sources and regulation of RANKL and OPG in physiological bone turnover as well as under pathological (osteoporotic) conditions continue to be made, opening a window to the complex regulatory processes that control skeletal integrity and the depth of integration of the skeleton within the immune response. This paper will examine the interconnection between bone turnover and the immune system and the implications thereof for physiological and pathological bone turnover.
Collapse
Affiliation(s)
- M. Neale Weitzmann
- Atlanta Department of Veterans Affairs Medical Center, Decatur, GA 30033, USA
- Division of Endocrinology and Metabolism and Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, 1305 WMRB, Atlanta, GA 30322, USA
| |
Collapse
|
|
43
|
Gutierrez H, Kisiswa L, O'Keeffe GW, Smithen MJ, Wyatt S, Davies AM. Regulation of neurite growth by tumour necrosis superfamily member RANKL. Open Biol 2013; 3:120150. [PMID: 23303310 PMCID: PMC3603457 DOI: 10.1098/rsob.120150] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
RANKL (receptor-activator of NF-κB ligand, TNFSF11) is a member of the TNF superfamily that regulates bone remodelling and the development of the thymus, lymph nodes and mammary glands. While RANKL and its membrane bound receptor RANK (TNFRSF11A) are expressed in the adult central nervous system and have been implicated in thermoregulation, the potential function of RANK signalling in the developing nervous system remains unexplored. Here, we show that RANK is expressed by sympathetic and sensory neurons of the developing mouse peripheral nervous system and that activating RANK signalling in these neurons during perinatal development by either treating cultured neurons with soluble RANKL or overexpressing RANK in the neurons inhibited neurotrophin-promoted neurite growth without affecting neurotrophin-promoted neuronal survival. RANKL is expressed in tissues innervated by these neurons, and studies in compartment cultures demonstrated that RANKL is capable of acting directly on neurites to inhibit growth locally. Enhancing RANK signalling in cultured neurons resulted in NF-κB activation and phosphorylation of the p65 NF-κB subunit on serine 536. Transfecting neurons with a series of mutated signalling proteins showed that NF-κB activation and p65 phosphorylation occurred by an IKKβ-dependent mechanism and that blockade of this signalling pathway prevented neurite growth inhibition by RANKL. These findings reveal that RANKL is a novel negative regulator of neurite growth from developing PNS neurons and that it exerts its effects by IKKβ-dependent activation of NF-κB.
Collapse
Affiliation(s)
- Humberto Gutierrez
- Cardiff School of Biosciences, Cardiff University, Cardiff Wales CF10 3AX, UK
| | | | | | | | | | | |
Collapse
|
|
44
|
dos Santos PL, Queiroz TP, Margonar R, Gomes de Souza Carvalho AC, Okamoto R, de Souza Faloni AP, Garcia IR. Guided implant surgery: what is the influence of this new technique on bone cell viability? J Oral Maxillofac Surg 2013; 71:505-12. [PMID: 23298799 DOI: 10.1016/j.joms.2012.10.017] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Revised: 10/01/2012] [Accepted: 10/15/2012] [Indexed: 11/26/2022]
Abstract
PURPOSE To evaluate the effect of implant osteotomy on immediate bone cell viability, comparing guided surgery for implant placement with the classic drilling procedure. MATERIALS AND METHODS For this study, 20 rabbits were used. The animals were divided into a guided surgery group (GG) and a control group (CG) and were then divided into 4 subgroups--subgroups 1, 2, 3, and 4--corresponding to drills used 10, 20, 30, and 40 times, respectively. All animals received 5 osteotomies in each tibia, by use of the classic drilling procedure in one tibia and guided surgery in the other tibia. The osteotomized areas were removed and processed immunohistochemically for detection of osteocalcin, receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and caspase 3. RESULTS Immunohistochemical analysis showed that osteocalcin expression was initially higher in the CG and remained constant after drill reutilization. Although the expressions of RANKL and OPG were not statistically different for the GG and CG, the RANKL/OPG ratio tended to be higher for the GG. Moreover, caspase 3 expression was elevated in the GG, proportionally to the number of osteotomies, indicating an increase in the apoptosis index in the GG. CONCLUSIONS The classic drilling procedure is more favorable to cell viability than guided surgery.
Collapse
Affiliation(s)
- Pâmela Letícia dos Santos
- Department of Surgery and Integrated Clinic, Discipline of Oral and Maxillofacial Surgery, Universidade Estadual Paulista-UNESP, Araçatuba, Brazil.
| | | | | | | | | | | | | |
Collapse
|
|
45
|
Hasan KMM, Rahman MS, Arif KMT, Sobhani ME. Psychological stress and aging: role of glucocorticoids (GCs). AGE (DORDRECHT, NETHERLANDS) 2012; 34:1421-1433. [PMID: 21971999 PMCID: PMC3528378 DOI: 10.1007/s11357-011-9319-0] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/19/2011] [Accepted: 09/19/2011] [Indexed: 05/31/2023]
Abstract
Psychological stress has extreme adverse consequences on health. However, the molecular mechanisms that mediate and accelerate the process of aging due to stress hormone are not well defined. This review has focused on diverse molecular paths that come out in response to chronic psychological stress via releasing of excessive glucocorticoids (GCs), involved in the aging process. GCs suppress transcription of nuclear cell adhesion molecules which impair synaptic plasticity, memory formation, and cognitive ability. Again, GCs promote muscle atrophy by means of motivating ubiquitin proteasome system and can repress muscle protein synthesis by inhibition of PI3-kinase/Akt pathway. GCs also inhibit interleukin-2 synthesis through suppressing T cell receptor signal that leads to loss of T cell activation, proliferation, and B-cell activation. Moreover, GCs increase the expression of collagenase-3, RANK ligand, and colony stimulating factor-1 that induce bone resorption. In general, stress-induced GCs can play causal role for aging and age-related disorders.
Collapse
Affiliation(s)
- K. M. Mehedi Hasan
- Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, 9208 Bangladesh
| | - Md. Shaifur Rahman
- Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, 9208 Bangladesh
| | - K. M. T. Arif
- Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, 9208 Bangladesh
| | - Mahbub E. Sobhani
- Biotechnology and Genetic Engineering Discipline, Khulna University, Khulna, 9208 Bangladesh
| |
Collapse
|
|
46
|
Brennan O, Kuliwaba JS, Lee TC, Parkinson IH, Fazzalari NL, McNamara LM, O'Brien FJ. Temporal changes in bone composition, architecture, and strength following estrogen deficiency in osteoporosis. Calcif Tissue Int 2012; 91:440-9. [PMID: 23076448 DOI: 10.1007/s00223-012-9657-7] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2012] [Accepted: 08/12/2012] [Indexed: 01/22/2023]
Abstract
Using an ovariectomized (OVX) ovine model, we provide an analysis of the timing of changes in bone following estrogen deficiency. The expression of genes known to regulate osteoclastogenesis, matrix production, and mineralization, as measured by real-time RT-PCR, was significantly increased by 12 months; and increased expression was maintained through to 31 months post-OVX compared to controls. FTIR spectroscopy confirmed that mineralized crystals were less mature than in controls 12 months post-OVX and were even less so by 31 months. The mineral-to-matrix ratio was significantly reduced by 31 months, while the ratio of mature to immature collagen cross-linking was initially increased at 12 months and subsequently reduced at 31 months post-OVX. In contrast, trabecular number, thickness, and separation were unchanged at 12 months. Significant reductions in trabecular number and thickness and a significant increase in trabecular separation were observed 31 months after OVX. Most notably perhaps these combined changes led to a significant reduction in the compressive strength of trabecular bone after 31 months. The results indicate that there is an initial increase in bone turnover, which is accompanied by a change in bone composition. This is followed by a continued increase in bone resorption and relative reduction in bone formation, leading to deterioration in bone microarchitecture. Ultimately, these cumulative changes led to a significant reduction in the compressive strength of bones following 31 months of estrogen deficiency. These findings provide important insight into the time sequence of changes during osteoporosis.
Collapse
Affiliation(s)
- Orlaith Brennan
- Department of Anatomy, Royal College of Surgeons in Ireland, 123, St. Stephen's Green, Dublin 2, Ireland
| | | | | | | | | | | | | |
Collapse
|
|
47
|
Effects and interaction of icariin, curculigoside, and berberine in er-xian decoction, a traditional chinese medicinal formula, on osteoclastic bone resorption. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2012; 2012:490843. [PMID: 23243450 PMCID: PMC3519276 DOI: 10.1155/2012/490843] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2012] [Revised: 09/09/2012] [Accepted: 09/24/2012] [Indexed: 11/28/2022]
Abstract
Er-Xian decoction (EXD), a traditional Chinese medicine, has been reported to have a protective effect against bone loss in ovariectomized osteoporotic rats, and the inclusion of icariin (I), curculigoside (C), and berberine (B) in EXD displays inhibitory effects on osteoclastic bone resorption. In the present paper, we investigated the interaction and effects of I, C, B, and their combination on bone resorption activity in vitro on osteoclasts derived from rat bone marrow cells. ICB synergistically decreased the formation of bone resorption pits, the number of multinucleated osteoclasts, and the activity of tartrate-resistant acid phosphatase (TRAP) and showed antagonistic or additive effects on cathepsin K activity in the coculture system of osteoblasts and bone marrow cells in the presence of 1, 25-dihydroxyvitamin D3 and dexamethasone. The combination of ICB also enhanced the inhibitory effects on the formation of F-actin ring, a cytoskeleton structure of osteoclasts induced from bone marrow cells with macrophage colony stimulation factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). In addition, ICB synergistically improved the ratio of protein expression of osteoprotegerin (OPG) and RANKL in osteoblasts and interfered with the mitogen-activated protein kinases (MAPKs) pathway in osteoclast. These results clearly show that I, C, B, and their combination in EXD exert effects of mutual reinforcement. However, IBC does not show an intensified adverse effect in the ovariectomized murine model, as revealed by change in body and uterine weight, confirming the safety of EXD. These observations are in agreement with the rationality of the formula used in this paper.
Collapse
|
|
48
|
Martin PL, Bugelski PJ. Concordance of preclinical and clinical pharmacology and toxicology of monoclonal antibodies and fusion proteins: soluble targets. Br J Pharmacol 2012; 166:806-22. [PMID: 22168335 DOI: 10.1111/j.1476-5381.2011.01812.x] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Monoclonal antibodies (mAbs) and fusion proteins directed towards soluble targets make an important contribution to the treatment of disease. The purpose of this review was to correlate the clinical and preclinical data on the 14 currently approved mAbs and fusion proteins targeted to soluble targets. The principal sources used to gather data were: the peer reviewed Literature; European Medicines Agency 'Scientific Discussions' and United States Food and Drug Administration 'Pharmacology/Toxicology Reviews' and package inserts (United States Prescribing Information). Data on the following approved biopharmaceuticals were included: adalimumab, anakinra, bevacizumab, canakinumab, certolizumab pegol, denosumab, eculizumab, etanercept, golimumab, infliximab, omalizumab, ranibizumab, rilonacept and ustekinumab. Some related biopharmaceuticals in late-stage development were also included for comparison. Good concordance with human pharmacodynamics was found for both non-human primates (NHPs) receiving the human biopharmaceutical and mice receiving rodent homologues (surrogates). In contrast, there was limited concordance for human adverse effects in genetically deficient mice, mice receiving surrogates or NHPs receiving the human pharmaceutical. In summary, the results of this survey show that although both mice and NHPs have good predictive value for human pharmacodynamics, neither species have good predictive value for human adverse effects. No evidence that NHPs have superior predictive value was found.
Collapse
Affiliation(s)
- Pauline L Martin
- Biologics Toxicology, Janssen Research & Development, Radnor, PA 19087, USA.
| | | |
Collapse
|
|
49
|
Adeno-associated virus-mediated osteoprotegerin gene transfer protects against joint destruction in a collagen-induced arthritis rat model. Joint Bone Spine 2012; 79:482-7. [DOI: 10.1016/j.jbspin.2011.10.011] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2011] [Accepted: 10/03/2011] [Indexed: 12/14/2022]
|
|
50
|
Choe WS, Kim HL, Han JK, Choi YE, Seo B, Cho HJ, Yang HK, Park KJ, Park JS, Park HJ, Kim PJ, Baek SH, Seung KB, Kim HS. Association between OPG, RANK and RANKL gene polymorphisms and susceptibility to acute coronary syndrome in Korean population. J Genet 2012; 91:87-9. [PMID: 22546829 DOI: 10.1007/s12041-012-0131-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Won-Seok Choe
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744, Republic of Korea
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|