DOCSLIB.ORG

Role in Inflammation and Bone Loss

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role in Inflammation and Bone Loss Editorial The Osteoprotegerin/Osteoprotegerin Ligand Family: Role in Inflammation and Bone Loss There is much excitement surrounding osteoprotegerin upregulated by many soluble factors affecting bone resorp- (OPG), its osteoprotegerin ligand (OPGL), and their role in tion, including the proinflammatory cytokines, interleukin-1 bone metabolism. Bone growth and remodeling is a and TNF-α 11,12. T cells express a cell-surface membrane- dynamic process, balancing bone matrix synthesis by bound OPGL that is cleaved by metalloproteinases into a osteoblasts and resorption of bone by multinucleated osteo- soluble form13. There may be some functional differences clasts1,2. Osteoprotegerin ligand, a member of the tumor between membrane-bound and soluble OPGL, with cell- necrosis factor receptor family of molecules, is a key regu- bound OPGL being more effective mediators of osteoclasto- lator of bone remodeling through its key role in osteoclasto- genesis when measured by in vitro assays13. The presence of genesis3-6. both soluble and membrane-bound forms of OPGL and their OPGL was discovered by several groups, and was given functional differences may explain the conflicting data from different names depending on the reason behind its different groups. The method of quantitation of OPGL and discovery: TRANCE [tumor necrosis factor (TNF) related the specimen used may also help address these differences. activation induced cytokine]7, RANKL [receptor activator Investigators using ELISA assays on serum can only of nuclear factor-κB (RANK) ligand]8, osteoclast differenti- measure the soluble form, as in the report by Masi, et al. ation factor4, and OPGL ligand for OPG3. In addition to its Those researchers using flow cytometry on single cell essential role in the development and activation of osteo- suspensions will only measure cell-bound forms of OPGL, clasts, OPGL has been identified as an important costimula- and those using reverse transcription polymerase chain reac- tion molecule involved in T cell–dendritic cell communi- tion (RT-PCR) to quantitate messenger RNA production will cation and in dendritic cell survival8,9. RANK is the measure message precursors for both soluble and downstream signaling receptor for OPGL. OPG is a soluble membrane-bound variants. decoy receptor for OPGL, neutralizing its ability to bind In the article presented in this issue, Masi, et al report with RANK and induce a signal. Due to its expression on that serum levels of OPGL protein, as measured by ELISA, activated T cells and its role in inflammation and bone loss, in children with JIA are lower than those for healthy chil- OPGL has generated much interest in autoimmune disease dren. This would point to decreased osteoclastic activity in research, in particular in inflammatory arthritis. children with JIA compared to healthy children, a counter- In this issue of The Journal, Masi and colleagues inves- intuitive notion, given the body of literature demonstrating tigate the role of the OPG/OPGL system in modulating bone the increased risk and incidence of osteopenia in children injury in children with juvenile idiopathic arthritis (JIA)10. with JIA. Data from Varsani, et al14 and our own data15 They report an increased OPG/OPGL ratio in the peripheral differ from those reported by Masi, in finding an increased blood of children with JIA compared to controls, as well as level of OPGL in the peripheral circulation of children with the association of the TT polymorphism of the OPG gene in JIA compared to healthy children. The critical difference is children with JIA with lower bone mineral density. The the method of quantitation of OPGL. In Varsani’s case and authors suggest that increased OPG production in affected in ours, RT-PCR was used to measure OPGL mRNA, which children may reflect a compensatory mechanism for over- represents precursors of both soluble and membrane-bound production of OPGL. forms. The increase in OPGL in children with JIA is also seen when OPGL is assayed by flow cytometry, which THE OPG/OPGL PATHWAY measures cell-surface, membrane-bound forms of OPGL. OPGL is made by activated T cells and its expression is These differences serve to highlight the need to further See Osteoprotegerin/RANK-L System in JIA: Is there a potential modulating role for OPG/RANK-L in bone injury?, page 986 Personal, non-commercial use only. The Journal of Rheumatology Copyright © 2004. All rights reserved. Personal,844 non-commercial use only. The Journal of Rheumatology. CopyrightThe Journal © 2004. of Rheumatology All rights 2004; reserved. 31:5 Downloaded on September 25, 2021 from www.jrheum.org understand the biologic activity of membrane-bound versus In contrast, cytokines inhibiting osteoclastogenesis, such soluble forms of OPGL to accurately interpret data within as IL-13, interferon-γ, and transforming growth factor-ß1 the context of disease and normal physiologic states. suppress the expression of OPGL but enhance expression of Another important factor in the physiologic equation is its inhibitor OPG13. Interestingly, glucocorticoids, widely the interactions of OPGL with its natural decoy used to treat multisystem autoimmune disease and arthritis, receptor/neutralizer, OPG. Bone loss mediated by OPGL strongly induce OPGL expression and decrease expression can be blocked by administration of OPG16. OPG functions of its decoy receptor, OPG20,21. One of the well documented as a decoy receptor for OPGL, competing with RANK for morbidities of corticosteroid use is bone loss. binding with OPGL, effectively inhibiting osteoclastogen- In people with inflammatory arthritis, OPGL has also esis both in vitro and in vivo17. Thus evaluation of OPGL emerged as an important factor regulating bone loss. levels must go hand in hand with OPG levels, as the balance Synovial tissue from patients with rheumatoid arthritis and of the 2 will determine whether osteoclastic or osteoblastic osteoarthritis have been shown to express high levels of activity dominates. OPGL16. Similarly, patients with spondyloarthropathies However, this evaluation is not a simple one-to-one have also been found to express high levels of OPGL in calculation: OPG, although a member of the TNF receptor affected synovial tissue22. There remains debate whether super family, is secreted as a 110 kDa homodimer, not a cartilage destruction occurs independently or is dependent molecular trimer, as are others in this molecular family on subchondral bone loss23. In the adjuvant-induced rat including its ligand OPGL17. The report by Masi and arthritis model, both cartilage and bone are protected by colleagues shows that the ratio of OPG/OPGL is lower in administration of OPG16, but in collagen-induced arthritis in the peripheral blood of children with JIA compared with rats, the protective effects of OPG were less in cartilage than healthy controls, again opposite to what one would expect in in bone24. In patients with erosive psoriatic arthritis, an osteopenic scenario. increased numbers of osteoclast precursors (OCP) were The interaction of OPGL and OPG at the molecular level found in the peripheral blood. OCP numbers were decreased is not known. One way to assist in data interpretation is to by administration of OPG and anti-TNF25. link the determinations of OPGL and OPG with biologic Although administration of OPG in animal models of activity, in this case osteoclastogenesis leading to bone loss, arthritis is bone protective, inflammation and its systemic a biologically relevant measure of activity in the effects are not altered18,26. Many cell types, both immune OPG/OPGL pathway. To that end, investigators have quan- and non-immune, have now been found to express OPGL titated the presence of osteoclast precursors and their func- including lymphocytes, monocytes, macrophages, dendritic tional ability to resorb bone as a correlate to OPGL levels cells, synovial fibroblasts, and mammary gland epithelial and the balance of activities between OPGL and OPG. Proof cells of lactating females16,27,28. Additionally, the down- of principle would include neutralization of this OPGL- stream effects of inflammatory cytokines on the mediated biologic activity by exogenous OPG. OPG/OPGL pathway may be the temporal answer to the apparent “disconnect” between inflammation and bone loss OPGL, T CELLS, AND BONE LOSS in arthritis in some situations. This may in part explain the T cells appear to be the link between inflammation and bone lack of correlation between serum levels of members of the loss. Increasingly, the role of OPGL as a critical second OPG/OPGL family and classic markers of inflammation in signal involved in optimal T cell activation is recognized. T patients with arthritis. As reported by Masi, et al, there is no cell-derived OPGL can also regulate the development and correlation between OPG or OPGL and common laboratory activation of osteoclasts resulting in bone loss16. This mech- markers of inflammation such as erythrocyte sedimentation anism is true both for systemic and local activation of T rate or C-reactive protein, but genetic control of OPG cells. In Lewis rats, adjuvant arthritis is a T cell-dependent expression may be related to local bone loss and generalized disease leading to joint inflammation and bone erosions18. T osteopenia. cells from inflamed joints express OPGL16. Although T cells The OPG/OPGL pathway is a key regulator of bone appear to be important regulators of bone metabolism, metabolism through its effect on development and activa- mutant mice that lack T cells do not have abnormal bones or tion of osteoclasts. In addition to its role in osteoclastogen- dentition. But under conditions of chronic systemic activa- esis, OPGL is a critical factor in the immune system, from tion of T cells as in viral infections and multisystem autoim- regulating development of lymph nodes and Peyer’s patches mune disease, or chronic local inflammation involving bone to serving as an important costimulation molecule in and joints such as in arthritis, bone remodeling via produc- optimal T cell activation and mediating dendritic cell tion of OPGL by T cells plays a more prominent role19.
Load more

Recommended publications
  • TRAIL and Cardiovascular Disease—A Risk Factor Or Risk Marker: a Systematic Review
    Journal of Clinical Medicine Review TRAIL and Cardiovascular Disease—A Risk Factor or Risk Marker: A Systematic Review Katarzyna Kakareko 1,* , Alicja Rydzewska-Rosołowska 1 , Edyta Zbroch 2 and Tomasz Hryszko 1 1 2nd Department of Nephrology and Hypertension with Dialysis Unit, Medical University of Białystok, 15-276 Białystok, Poland; [email protected] (A.R.-R.); [email protected] (T.H.) 2 Department of Internal Medicine and Hypertension, Medical University of Białystok, 15-276 Białystok, Poland; [email protected] * Correspondence: [email protected] Abstract: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a pro-apoptotic protein showing broad biological functions. Data from animal studies indicate that TRAIL may possibly contribute to the pathophysiology of cardiomyopathy, atherosclerosis, ischemic stroke and abdomi- nal aortic aneurysm. It has been also suggested that TRAIL might be useful in cardiovascular risk stratification. This systematic review aimed to evaluate whether TRAIL is a risk factor or risk marker in cardiovascular diseases (CVDs) focusing on major adverse cardiovascular events. Two databases (PubMed and Cochrane Library) were searched until December 2020 without a year limit in accor- dance to the PRISMA guidelines. A total of 63 eligible original studies were identified and included in our systematic review. Studies suggest an important role of TRAIL in disorders such as heart failure, myocardial infarction, atrial fibrillation, ischemic stroke, peripheral artery disease, and pul- monary and gestational hypertension. Most evidence associates reduced TRAIL levels and increased TRAIL-R2 concentration with all-cause mortality in patients with CVDs. It is, however, unclear Citation: Kakareko, K.; whether low TRAIL levels should be considered as a risk factor rather than a risk marker of CVDs.
    [Show full text]
  • Osteoprotegerin: a Novel Secreted Protein Involved in the Regulation of Bone Density
    Cell, Vol. 89, 309±319, April 18, 1997, Copyright 1997 by Cell Press Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density W. S. Simonet,2 D. L. Lacey,7 C. R. Dunstan,7 during normal bone remodeling that occurs throughout M. Kelley,3 M.-S. Chang,4 R. LuÈ thy,4 life. In contrast, osteoclasts differentiate from hemato- H. Q. Nguyen,2 S. Wooden,5 L. Bennett,6 poietic precursors of the monocyte±macrophage lin- T. Boone,10 G. Shimamoto,10 M. DeRose,2 eage and resorb bone matrix. Both these cell types are R. Elliott,1 A. Colombero,1 H.-L. Tan,7 influenced by a wide variety of hormones, inflammatory G. Trail,5 J. Sullivan,8 E. Davy,3 N. Bucay,2 mediators, and growth factors (Suda et al., 1992; Mundy, L. Renshaw-Gegg,5 T. M. Hughes,2 D. Hill,7 1993a, 1993b). An imbalance of osteoblast and osteo- W. Pattison,4 P. Campbell,6 S. Sander,5 clast functions can result in skeletal abnormalities char- G. Van,7 J. Tarpley,7 P. Derby,9 R. Lee,10 acterized by increased (osteopetrosis) or decreased (os- Amgen EST Program, and W. J. Boyle1 teoporosis) bone mass. 1 Department of Cell Biology The study of osteopetrosis in mutant mice has led to 2 Department of Molecular Genetics significant advances in the understanding of the pro- 3 Department of Protein Chemistry cesses that regulate bone mass (Marks, 1989). From 4 Department of Computational Biology these studies we have learned the following: (i) genetic 5 Department of Mammalian Cell Molecular Biology defects in osteoclast development, maturation, and/or 6 Department of Immunology activation lead to decreased bone resorption and uni- 7 Department of Pathology formly result in severe osteopetrosis (Marks, 1989); (ii) 8 Department of Bacterial Expression the stromal microenvironment plays an essential role in osteoclast differentiation (Udagawa et al., 1989); (iii) 9 Department of Protein Structure signal transduction from the cell membrane through Src 10 Department of Process Science tyrosine kinase is necessary for osteoclast-mediated Amgen Inc.
    [Show full text]
  • Belantamab Mafodotin to Treat Multiple Myeloma: a Comprehensive Review of Disease, Drug Efficacy and Side Effects
    Review Belantamab Mafodotin to Treat Multiple Myeloma: A Comprehensive Review of Disease, Drug Efficacy and Side Effects Grace Lassiter 1,*, Cole Bergeron 2, Ryan Guedry 2, Julia Cucarola 2, Adam M. Kaye 3 , Elyse M. Cornett 4, Alan D. Kaye 4 , Giustino Varrassi 5, Omar Viswanath 4,6,7,8 and Ivan Urits 4,9 1 School of Medicine, Georgetown University, Washington, DC 20007, USA 2 School of Medicine, Louisiana State University Shreveport, Shreveport, LA 71103, USA; [email protected] (C.B.); [email protected] (R.G.); [email protected] (J.C.) 3 Department of Pharmacy Practice, Thomas J. Long School of Pharmacy and Health Sciences, University of the Pacific, Stockton, CA 95211, USA; akaye@pacific.edu 4 Department of Anesthesiology, Louisiana State University Shreveport, Shreveport, LA 71103, USA; [email protected] (E.M.C.); [email protected] (A.D.K.); [email protected] (O.V.); [email protected] (I.U.) 5 Paolo Procacci Foundation, Via Tacito 7, 00193 Roma, Italy; [email protected] 6 College of Medicine-Phoenix, University of Arizona, Phoenix, AZ 85724, USA 7 Department of Anesthesiology, School of Medicine, Creighton University, Omaha, NE 68124, USA 8 Valley Anesthesiology and Pain Consultants—Envision Physician Services, Phoenix, AZ 85004, USA 9 Southcoast Health, Southcoast Physicians Group Pain Medicine, Wareham, MA 02571, USA * Correspondence: [email protected] Received: 14 December 2020; Accepted: 18 January 2021; Published: 21 January 2021 Abstract: Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time.
    [Show full text]
  • TNF Receptor Superfamily Members RANK, RANKL, OPG Pathway As
    RESEARCH ARTICLE TNF Receptor Superfamily Members RANK, RANKL, OPG Pathway as Osteoimmunological Biomarker of Bone Healing after Orthognathic Surgery İhsan O Osar1, Yavuz Fındık2, Orhan Akpinar3 ABSTRACT Tumor necrosis factor (TNF) receptor superfamily member receptor activator of nuclear factor-κB (RANK), RANK-ligand (RANKL), and osteoprotegerin (OPG) pathway as osteoimmunological biomarker of bone healing after surgery. These biomarkers play an important role in the bone repair and healing after orthognathic surgery. The aim of our study was to evaluate levels of the RANKL–RANK–OPG cytokine system as osteoimmunological biomarker of bone healing after orthognathic surgery. Receptor activator of nuclear factor-κB, RANKL, and OPG were evaluated in 25 patients who is undergoing orthognathic surgery. Blood samples were collected before the operation, after 1st day, and 10th day of the operation. Differences among OPG, RANK, and RANKL averages were not statistically significant in all time levels and operation types. In this study, we concluded that RANKL/OPG ratio and blood serum RANK levels may show bone remodeling activity and bone remodeling activity after orthognathic surgery, although there is a need for further extensive studies. Keywords: Biomarker, General anesthesia, Orthognathic surgery. International Journal of Experimental Dental Science (2020): 10.5005/jp-journals-10029-1201 INTRODUCTION 1–3Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Orthognathic surgery is the main procedure for the correction Süleyman Demirel University, Isparta, Turkey of jaw function and esthetics of the face. Orthognathic surgery Corresponding Author: Yavuz Fındık, Department of Oral and is performed on the surgeon’s bone, but the processes on the Maxillofacial Surgery, Faculty of Dentistry, Süleyman Demirel University, bone activate the bone formation and destruction events on this Isparta, Turkey, Phone: +902462113251, e-mail: yavuzfindik32@ tissue.
    [Show full text]
  • Trailblazing Strategies for Cancer Treatment
    cancers Review TRAILblazing Strategies for Cancer Treatment Anna-Laura Kretz 1, Anna Trauzold 2,3, Andreas Hillenbrand 1, Uwe Knippschild 1, Doris Henne-Bruns 1, Silvia von Karstedt 4,5 and Johannes Lemke 1,* 1 Department of General and Visceral Surgery, Ulm University Hospital, Albert-Einstein-Allee 23, 89081 Ulm, Germany; [email protected] (A.-L.K.); [email protected] (A.H.); [email protected] (U.K.); [email protected] (D.H.-B.) 2 Institute for Experimental Cancer Research, University of Kiel, 24105 Kiel, Germany; [email protected] 3 Clinic for General Surgery, Visceral, Thoracic, Transplantation and Pediatric Surgery, University Hospital Schleswig-Holstein, 24105 Kiel, Germany 4 Department of Translational Genomics, University Hospital Cologne, Weyertal 115b, 50931 Cologne, Germany; [email protected] 5 Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne, Joseph-Stelzmann Straße 26, 50931 Cologne, Germany * Correspondence: [email protected] Received: 11 March 2019; Accepted: 26 March 2019; Published: 30 March 2019 Abstract: In the late 1990s, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF-family, started receiving much attention for its potential in cancer therapy, due to its capacity to induce apoptosis selectively in tumour cells in vivo. TRAIL binds to its membrane-bound death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) inducing the formation of a death-inducing signalling complex (DISC) thereby activating the apoptotic cascade. The ability of TRAIL to also induce apoptosis independently of p53 makes TRAIL a promising anticancer agent, especially in p53-mutated tumour entities.
    [Show full text]
  • Alterations in the Immuno-Skeletal Interface Drive Bone Destruction in HIV-1 Transgenic Rats
    Alterations in the immuno-skeletal interface drive bone destruction in HIV-1 transgenic rats Tatyana Vikulinaa,1, Xian Fanb,c,1, Masayoshi Yamaguchia, Susanne Roser-Pagec, Majd Zayzafoond, David M. Guidotb,c, Ighovwerha Ofotokune, and M. Neale Weitzmanna,c,f,2 Divisions of aEndocrinology and Metabolism and Lipids and bPulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322; cAtlanta Veterans Affairs Medical Center, Decatur, GA 30033; dDepartment of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294; eDivision of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322; and fWinship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322 Edited* by Max D. Cooper, Emory University, Atlanta, GA, and approved June 24, 2010 (received for review March 10, 2010) Osteoporosis and bone fractures are increasingly recognized compli- capable of making RANKL and OPG, B cells are recognized as cations of HIV-1 infection. Although antiretroviral therapy itself has a significant source of RANKL when activated in vitro (13), in complex effects on bone turnover, it is now evident that the majority postmenopausal humans in vivo (3), and in inflammatory con- of HIV-infected individuals already exhibit reduced bone mineral ditions such as periodontitis (14). By contrast, both human (15) density before therapy. The mechanisms responsible are likely multi- and mouse B cells (1) are recognized producers of OPG, which is factorial and have been difficult to delineate in humans. The HIV-1 regulated, in part, by T cells through CD40/CD40 ligand (CD40L) transgenic rat recapitulates many key features of human AIDS.
    [Show full text]
  • Genieplex Quantitative Multiplex Immunoassays
    GeniePlex Quantitative Multiplex Immunoassays Quantitatively Measure 1-24 Analytes Per Sample! ELISA Genie: Maximum Support ELISA Genie is а proprietary range of ELISA kits & multiplex assays developed bу Reagent Genie, а global life science reagents company based in London and Dublin. Founded bу Colm Ryan PhD and Seán Mac Fhearraigh PhD, our goal is to provide you with premium quality ELISA kits along with excellent technical and logistics support, so you саn maximise your success. GeniePlex Multiplex Immunoassays GeniePlex: Quantitively Measure 1-24 Analytes Simultaneously! GeniePlex is a bead-based multiplex immunoassay technology. It enables the simultaneous & quantitative detection of up to 24 analytes in as little as 15 μl sample on almost any flow cytometer. It’s like doing 24 different ELISA in every well! Phenomenal Performance Very Sensitive: Measure as low as <10 pg/ml of each analyte Excellent Dynamic Range: Lower limit < 20 pg/mL | Upper limit > 5,000 pg/mL High Precision & Accuracy: Intra-assay CV: < 10% | Inter-assay CV: < 20% | Recovery: 70-130% Low Sample Volumes: Use as little as 15 µl of sample Validated: All assays fully tested for cross-reactivity in our lab Unbeatable Flexibility Comprehensive Choice of Targets: Up to 400 assays & custom formats available for human, mouse, rat, porcine, canine and primates Wide Range of Sample Types: Cell culture supernatants, saliva, plasma, cell/tissue lysates, serum, BALF, pleural and peritoneal fluids & more Multiple Formats: 32-well and 96-well sizes available Convenience Redefined Use Your Own Lab: Assays can be run on most validated flow cytometers (PE & either PE-Cy5 or APC detectors) Free Software: Analyse with commonly available software such as FCAP Software v3.0.
    [Show full text]
  • OX40L Blockade Is Therapeutic in Arthritis, Despite Promoting Osteoclastogenesis
    OX40L blockade is therapeutic in arthritis, despite promoting osteoclastogenesis Emily Gwyer Findlaya,1,2, Lynett Danksb,1, Jodie Maddena, Mary M. Cavanagha, Kay McNameeb, Fiona McCannb, Robert J. Snelgrovea, Stevan Shawc, Marc Feldmannd,3, Peter Charles Taylord, Nicole J. Horwoodd, and Tracy Hussella,3,4 aLeukocyte Biology Section, National Heart and Lung Institute, Imperial College London, London SW7 2AZ, United Kingdom; bKennedy Institute of Rheumatology, London W6 8LH, United Kingdom; cUCB Pharma, Slough SL1 4EN, United Kingdom; and dNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, United Kingdom Contributed by Marc Feldmann, November 19, 2013 (sent for review May 16, 2013) An immune response is essential for protection against infection, The TNF superfamily member OX40 (CD134) is induced 24 to but, in many individuals, aberrant responses against self tissues 48 h after T-cell activation and binds the equally inducible OX40 cause autoimmune diseases such as rheumatoid arthritis (RA). ligand (OX40L) on antigen-presenting cells (APCs), causing a bi- How to diminish the autoimmune response while not augmenting directional activating signal to both cells. OX40 signaling promotes infectious risk is a challenge. Modern targeted therapies such as T-cell survival and their division and cytokine production, and, in anti-TNF or anti-CD20 antibodies ameliorate disease, but at the APCs, OX40L signaling causes maturation and the release of in- cost of some increase in infectious risk. Approaches that might flammatory mediators (7), or, in the case of B cells, increased IgG specifically reduce autoimmunity and tissue damage without production (8).
    [Show full text]
  • Immunosurveillance Function, and Modulation of NK Cell Acute
    Receptor Activator for NF-κB Ligand in Acute Myeloid Leukemia: Expression, Function, and Modulation of NK Cell Immunosurveillance This information is current as of September 27, 2021. Benjamin Joachim Schmiedel, Tina Nuebling, Julia Steinbacher, Alexandra Malinovska, Constantin Maximilian Wende, Miyuki Azuma, Pascal Schneider, Ludger Grosse-Hovest and Helmut Rainer Salih J Immunol 2013; 190:821-831; Prepublished online 14 Downloaded from December 2012; doi: 10.4049/jimmunol.1201792 http://www.jimmunol.org/content/190/2/821 http://www.jimmunol.org/ Supplementary http://www.jimmunol.org/content/suppl/2012/12/14/jimmunol.120179 Material 2.DC1 References This article cites 49 articles, 21 of which you can access for free at: http://www.jimmunol.org/content/190/2/821.full#ref-list-1 by guest on September 27, 2021 Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013
    [Show full text]
  • Adipose-Derived Stem Cell-Released Osteoprotegerin Protects
    Lee et al. Stem Cell Research & Therapy (2017) 8:195 DOI 10.1186/s13287-017-0647-6 SHORT REPORT Open Access Adipose-derived stem cell-released osteoprotegerin protects cardiomyocytes from reactive oxygen species-induced cell death Jiyun Lee1†, Seahyung Lee2†, Chang Youn Lee3, Hyang-Hee Seo1, Sunhye Shin3, Jung-Won Choi2,4, Sang Woo Kim2, Jong-Chul Park1,5, Soyeon Lim2* and Ki-Chul Hwang2* Abstract Background: The paracrine effect is likely the major mechanism of the adipose-derived stem cell (ASC)-mediated cardioprotective effect. However, the exact composition and nature of ASC-released paracrine factors remain elusive. In the present study, we examined the effect of osteoprotegerin (OPG), a stem cell-released decoy receptor for death ligand, on the survival of cardiomyocytes exposed to oxidative stress. Methods: The production of OPG from ASCs under oxidative stress was determined by ELISA and immunohistochemistry. The effects of OPG and the OPG-containing conditioned media of ASCs on the survival of cardiomyocytes were determined using a cell viability assay. Results: Hydrogen peroxide (H2O2) significantly increased OPG production from ASCs in vitro, and OPG production from the ASCs transplanted into the ischemia–reperfusion-injured heart was also observed. OPG significantly attenuated cardiomyocyte death in vitro. OPG-containing conditioned media of ASCs also significantly protected cardiomyocytes. Delivery of siRNA specific to OPG significantly decreased the OPG production of ASCs, and also offset the protective effect of the conditioned media of ASCs. Conclusions: Our study strongly suggests that OPG is one of the prosurvival factors released from ASCs that may contribute to the ASC-mediated cardioprotection and calls for further studies to elucidate detailed underlying mechanisms.
    [Show full text]
  • University of California, San Diego
    UNIVERSITY OF CALIFORNIA, SAN DIEGO Regulation of Thrombopoietin in Bone Marrow A Dissertation submitted in partial satisfaction of the Requirements for the degree Doctor of Philosophy in Biomedical Sciences by Bryan James McIntosh Committee in charge: Professor Kenneth Kaushansky, Chair Professor Gerald Boss Professor Christopher Glass Professor Lawrence Goldstein Professor Sanford J. Shattil 2007 Copyright Bryan James McIntosh, 2007 All rights reserved The dissertation of Bryan James McIntosh is approved, and is acceptable in quality and form for publication on microfilm: (Chair) University of California, San Diego 2007 iii TABLE OF CONTENTS Signature Page……………………………………………….………………………….. iii Table of Contents……………………………………………………………....……...... iv List of Figures………………………………………………………………...………….. v List of Schemes ……………………………………………………………….………… vi List of Tables …………………………………………………………..………………... vii List of Graphs ……………………………………………………………..…………….. viii Acknowledgements …………………………………………...…………………………ix Vita…………………………………………..………………………..………..………… x Abstract……………………………………………………………………..……..…….. xi Chapter1: Introduction and Background……………………………………..……… 1 Chapter 2: Transcriptional Regulation of Bone Marrow TPO by Platelet Proteins…………………………………………………………………...…6 Chapter 3: The Effect of Plasma on Bone Marrow TPO Expression…………………………………………………………………………….….26 Chapter 4: Alternative Hypotheses of TPO Regulation………………………….…..28 Chapter 5: Consideration of Potential Effects of Translation of TPO Transcript Stability ……………….……………….………....…...31 Chapter
    [Show full text]
  • The TNF Superfamily
    RnDSy-lu-2945 The TNF Superfamily TNF Homology Domain Ribbon Structure The TNF Superfamily Ligands Receptors The tumor necrosis factor (TNF) superfamily in humans currently consists of 19 ligands and 29 receptors, with three additional TNF family receptors 4-1BB Ligand having been identified in mice. Most TNF ligands are type II trans- membrane proteins with extracellular domains that can be cleaved by 4-1BB specific metalloproteinases to generate soluble cytokines. Cleaved and APRIL BCMA non-cleaved ligands are active as noncovalent homotrimers except for Lymphotoxin β, which forms heterotrimers with TNF-β/Lymphotoxin a BAFF TACI (LTa) and BAFF, which forms heterotrimers with APRIL. TNF family ligands are characterized by a stalk of varying length connecting the BAFF R transmembrane domain to the core region, which contains the hallmark CD27 structure of TNF family ligands, the TNF homology domain (THD). The CD27 Ligand CD30 THD is an anti-parallel β-pleated sheet sandwich with a “jelly-roll” topology. Conserved residues within the β strands provide specific inter- CD40 subunit contacts, which stabilize the trimeric structure. Sequences in the EDAR loops connecting adjacent β strands are family member-specific and are CD30 Ligand important for conferring receptor specificity. Receptors for TNF family XEDAR ligands are oligomeric, type I or type III transmembrane proteins that contain multiple extracellular cysteine-rich domains (CRDs). Several of CD40 Ligand Fas these receptors contain intracellular death domains (DDs) that recruit EDA-A1 caspase-interacting proteins to initiate apoptosis upon ligand binding. DcR3 Other TNF superfamily receptors that lack DDs bind TNF receptor- EDA-A2 GITR associated factors (TRAFs) and activate multiple intracellular signaling Fas Ligand pathways that can lead to proliferation or differentiation.
    [Show full text]