Download or read book Examining the Role of Autophagy in Osteoclast Function written by Anh Nhi Tran and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Osteoactivin Plays a Novel Role in Autophagy mediated Bone Homeostasis written by Fatima A. Jaber and published by . This book was released on 2018 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: Osteoporosis is a disease affecting most the population all over the world. There are some medications to treat this disease but with side effects. For example, bisphosphonates therapy has side effects including osteonecrosis. Therefore, it is important to discover new medications that increase bone formation and decrease bone resorption. Osteoactivin was discovered in an osteopetrotic mutant rat model. Our lab found that osteoactivin acts as anabolic factor to stimulate bone formation by osteoblasts. Autophagy is a catabolic process that allows cells to eliminate unwanted material. Autophagy related proteins have shown to be important for bone cells. Loss of autophagy could lead to dysfunction in bone homeostasis. In this study, we used the autophagy mTOR-independent and dependent pathways to determine its effects on osteoblast differentiation in vitro ex-vivo, and in vivo. First, we treated mesenchymal stem cells (MSCs) and osteoblast with Trehalose (TH) and Rapamycin (R) in culture, and found an increase in osteoblast differentiation and function determined by alkaline phosphatase (ALP) staining, activity, mineralization, and upregulation of osteoblast related gene expression. We found that treatment with TH and R stimulates osteoblast differentiation. Furthermore, we determined that treatments with TH causes induction of autophagosome formation associated with creating of double membrane of autophagic vacuoles in MC3T3-E1 osteoblast-like cells. Next, we wanted to determine if autophagy is important for osteoactivin mediated signaling in osteoblast. Our results have shown that osteoactivin co-localizes with microtubule-associated protein light chain 3II (LC3II), the main marker for autophagosome formation. Furthermore, we found that treatment with TH and R caused new bone formation in neonatal calvarial organ cultures from DBA/2J GPNMB+ and DBA/2J mice. Lastly, we found that osteoactivin enhanced osteoblast differentiation through the autophagy signaling pathway.In the next study, we wanted to determine the role of osteoactivin on osteoclast differentiation and function by mTOR-independent and dependent pathways. Our results revealed that osteoactivin inhibits osteoclast differentiation and size through mTOR-independent pathway but increases osteoclast function by the mTOR-dependent pathway in vitro study by TRAP staining and activity. While in vivo study showed that both autophagy pathways (mTOR-independent and dependent) causes increased osteoclast differentiation and bone resorption by TRAP staining and [mu]CT. Taken together, we believe that the osteoactivin and mTOR-dependent pathway rapamycin interact with each other to increase osteoblast differentiation, bone formation and osteoclast mediated resorption. However, mTOR-independent pathway by TH causes increased osteoblast differentiation, bone formation, and osteoclast differentiation.
Download or read book The Functions of Autophagy Genes in Lymphocytes and Osteoclasts written by Brian Christopher Miller and published by . This book was released on 2011 with total page 171 pages. Available in PDF, EPUB and Kindle. Book excerpt: Macroautophagy (herein autophagy) is a process by which cells degrade long-lived proteins and organelles. The autophagy pathway and autophagy genes have been implicated in many functions in the cell such as protecting against metabolic stress, degrading damaged organelles, and regulating vesicular trafficking. To study the role of autophagy in primary cells with important physiologic functions, we generated mice lacking essential autophagy genes in B lymphocytes, T lymphocytes, and osteoclasts. We found that the essential autophagy gene Atg5 was important for B cell development and for the maintenance of B-1a B cell numbers but not peripheral B-2 B cell numbers. In T cells, deletion of the essential autophagy genes Atg5 or Atg7 resulted in decreased thymocyte and peripheral T cell numbers in vivo and a decrease in cell proliferation in vitro. Autophagy genes play a critical role in T cell homeostasis, but do not appear important for peripheral B-2 B cell homeostasis in vivo. Whole-genome transcriptional profiling of Atg5-deficient and wild-type thymocytes suggested abnormalities in mitochondria in the absence of Atg5. We confirmed this observation by demonstrating that peripheral Atg5-deficient T cells had an increase in mitochondrial mass that correlated with increased Annexin-V staining in these cells. We speculate that autophagy is required in T cells for the removal of damaged or aged mitochondria and that excess mitochondria contribute to increased cell death in autophagy-deficient T cells. In contrast to lymphocytes, deletion of autophagy genes in osteoclasts did not result in dramatic abnormalities in cell development. However, the biochemical pathway necessary for autophagy was critical for directional secretion in osteoclasts. We found that the autophagosome marker LC3 localized to the resorptive microenvironment in osteoclasts. Deleting Atg5 or Atg7 or overexpressing a dominant negative mutant of ATG4B to inhibit LC3 conjugation reduced localization of lysosomal markers at the resorptive surface and decreased bone resorption in vitro. Furthermore, mice lacking Atg5 in osteoclasts and other myeloid-lineage cells were protected from ovarectomy-induced bone loss, a mouse model of osteoporosis. Together, these studies demonstrate that autophagy genes are important in cell development, survival, mitochondrial maintenance, and directional secretion in physiologically important, primary mammalian cells.
Download or read book Osteopetrosis Associated Transmembrane Protein 1 s Role in Autophagy and Lysosomal Biogenesis in Osteoclast Physiology written by Cameron Bauer and published by . This book was released on 2018 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Osteopetrosis is a disease characterized by the failure of osteoclasts (OCs) to resorb bone. As a consequence, bone mass is increased and bone marrow space is reduced; leading to premature death. The grey-lethal (gl/gl), Ostm1 null mouse model mimics severe human forms of osteopetrosis, and, although the exact function of OSTM1 in osteoclasts is not fully understood, OSTM1 is implicit in OC ruffled border (RB) formation. The RB is a platform for proton/protease excretion as well as bone material uptake and is formed through fusion of secretory lysosomes with RB membrane. Previous results have suggested that OSTM1 has a role in the lysosomal and autophagocytic pathways, thus we sought to elucidate these pathways in gl/gl osteoclasts with a pilot study on gl/gl MEF cells. Interestingly, in this study we found significant upregulation of autophagosomal markers such as p62 and LC3II/I in gl/gl osteoclasts which did not respond to enhanced autophagy via starvation as levels of autophagocytic proteins were already maxed out. This was similar to what was found in gl/gl MEFs, but without an increase found in LC3II/I. Dissimilarly to the gl/gl MEFs, in gl/gl OCs there was an accompanied mTOR inhibition. Furthermore, in both MEFs and OCs, we also detected an understimulated lysosomal compartment and a differential response in RAB7 (autolysosome adaptor protein) than in wild-type.Additionally, we sought to upregulate the lysosomal biogenesis with a hCtsk-Tfeb transgene, as Tfeb is a known master regulator of lysosomal biogenesis. The aim of this project was to enhance lysosomal biogenesis in gl/gl osteoclasts and restore proper function of the RB. Osteoclasts cultured from transgenic mice, did indeed show upregulation of lysosomal marking proteins, but this was not sufficient to rescue the osteopetrotic phenotype in gl/gl transgenic mice. In all this study showed that OSTM1 is intimately linked to autophagy and lysosomal function and has a special relationship with RAB7. Additionally, we showed that Tfeb upregulation has the potential to upregulate lysosomal biogenesis in OCs." --
Download or read book Current Advances in Osteosarcoma written by Eugenie S. Kleinerman, M.D. and published by Springer. This book was released on 2016-08-23 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Current Advances in Osteosarcoma edited by Dr. Eugenie S. Kleinerman summarizes molecular and genetic characteristics, new therapeutic ideas, and biological characteristics that have been uncovered in the past 10 years. Osteosarcoma is an aggressive malignant neoplasm and it is also the most common histological form of bone cancer. It accounts for approximately 56% of new bone tumors, making it the most primary malignant bone tumor in children and adolescents. The lungs are the most common site of metastases and once osteosarcoma spreads to the lungs, it is very difficult to treat. To improve the outcome of this disease, the biology of osteosarcoma needs to be better understood. There are numerous investigators around the world who have made seminal discoveries about the important molecular pathways and genetic alterations that contribute to the development and metastases of osteosarcoma. Other investigators have proposed novel therapeutic strategies including some based on the molecular and genetic phenotype of the disease. Current Advances in Osteosarcoma summarizes all of these new discoveries in one singular text, which will help move the field forward.
Download or read book Autophagy in Stem Cell Maintenance and Differentiation written by Bhupendra V. Shravage and published by Springer Nature. This book was released on 2022-11-08 with total page 290 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book covers a wide range of topics that illustrate the various functions of autophagy in stem cells and offers insights on the mechanisms by which autophagy can regulate stem-cell self-renewal and facilitate specific differentiation programs. Stem cells are unique cells present in most multicellular animals and are essential for their survival. They have two unique properties: the ability to self-renew and the ability to differentiate into one or more cell types. These characteristics of stem cells have found immense therapeutic potential in regenerative medicine. Autophagy is a crucial membrane trafficking pathway that is essential for maintaining cellular homeostasis that involves sequestration of non-functional proteins, protein aggregates and damaged organelles in double-membraned vesicles called autophagosomes, which are subsequently targeted to the lysosome for degradation. The primary aim of this book is to provide knowledge of recent developments in our understanding of the role of autophagy in stem cells, including germline stem cells. Autophagy is considered a promising target for many diseases. Significant efforts are being developed to identify specific modulators of autophagy, which will aid in designing combinatorial therapeutic strategies that will allow significant improvements in regenerative medicine.
Download or read book Glucocorticoid induced Osteoporosis written by Andrea Giustina and published by Karger Medical and Scientific Publishers. This book was released on 2002 with total page 213 pages. Available in PDF, EPUB and Kindle. Book excerpt: Osteoporosis is one of the most clinically relevant disabling chronic disease encountered in clinical practice. A common cause of osteoporosis is glucocorticoid excess, as glucocorticoids may increase bone resorption, inhibit bone formation, have indirect actions on bone by decreasing intestinal calcium absorption and induce hypercalciuria. This book presents a comprehensive overview of the effects of glucocorticoids on bone metabolism and structure and on the diagnosis and treatment of glucocorticoid-induced osteoporosis. It aims at providing updated information on the pathogenesis, diagnosis and treatment of this often dramatic complication of glucocorticoid excess. Being one of the few publications completely devoted to glucocorticoid-induced osteoporosis it will heighten the awareness of specialists who prescribe glucocorticoids of the clinical relevance of this treatment complication. 'Glucocorticoid-Induced Osteoporosis' is addressed to clinical experts as well as to general practitioners who will both benefit from the comprehensive and integrative view of the management of patients exposed to glucocorticoids.
Download or read book Updates on Osteoimmunology What s New on the Crosstalk Between Bone and Immune Cells written by Giacomina Brunetti and published by Frontiers Media SA. This book was released on 2020-03-24 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Autophagy Biology and Diseases written by Zheng-Hong Qin and published by Springer Nature. This book was released on 2019-11-27 with total page 727 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book series consists of 3 volumes covering the basic science (Volume 1), clinical science (Volume 2) and the technology and methodology (Volume 3) of autophagy. Volume 1 focuses on the biology of autophagy, including the signaling pathways, regulating processes and biological functions. Autophagy is a fundamental physiological process in eukaryotic cells. It not only regulates normal cellular homeostasis, and organ development and function, but also plays an important role in the pathogenesis of a wide range of human diseases. Thanks to the rapid development of molecular biology and omic technologies, research on autophagy has boomed in recent decades, and more and more cellular and animal models and state-of the-art technologies are being used to shed light on the complexity of signaling networks involved in the autophagic process. Further, its involvement in biological functions and the pathogenesis of various diseases has attracted increased attention around the globe. Presenting cutting-edge knowledge, this book series is a useful reference resource for researchers and clinicians who are working on or interested in autophagy.
Download or read book Autophagy in Health and Disease written by Kursad Turksen and published by Springer. This book was released on 2018-10-06 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt: This timely volume explores the impact of autophagy in various human diseases, emphasizing the cell biological aspects and focusing on therapeutic approaches to these diseases. The chapters cover autophagy and its potential applications on diseases ranging from obesity, osteoarthritis, pulmonary fibrosis, and inflammation, through ALS, Parkinson's, retinal degeneration, breast cancer, alcoholic liver disease and more. The final chapters round out the book with a discussion of autophagy in drug discovery and 'bench to bedside'. Chapters are contributed by leading authorities and describe the general concepts of autophagy in health and disease, marrying cell biology and pharmacology and covering: studies derived from preclinical experiments, manufacturing considerations,and regulatory requirements pertaining to drug discovery and manufacturing and production. This volume will be useful for basic scientists as well as already practicing clinicians and advanced graduate students.
Download or read book Comprehensive Review of Infectious Diseases written by Andrej Spec and published by Elsevier Health Sciences. This book was released on 2019-11-16 with total page 942 pages. Available in PDF, EPUB and Kindle. Book excerpt: Perfect for board review or quick reference in clinical practice, Comprehensive Review of Infectious Diseases is a balanced, high-yield resource covering the full range of infectious disease topics. Whether you're preparing for examinations or are looking for a concise resource to support your practice, this unique review contains precisely the information you need – from common infectious diseases concepts and conditions to hundreds of up-to-date review questions and answers for self-assessment and exam preparation. - Covers the most frequently encountered concepts and conditions in infectious diseases. - Covers challenging areas frequently covered on the boards: clinically-relevant microbiology and ID pharmacology, HIV and antiretroviral therapy, infections in immunocompromised hosts, dermatologic manifestations of ID, infection mimics, infection control and prevention, and more. - Includes new and emerging topics such as neglected tropical diseases, bioterrorism, and emerging and re-emerging infections. - Provides more than 550 case-based, board-style multiple-choice questions and answers for test prep and self-assessment. - Facilitates quick review and maximum retention of information by including hundreds of high-quality illustrations, tables, high-yield boxes, and bulleted lists. - Contains practical tips for taking the boards, buzzwords and memory aids for board questions, and clinical and board pearls. - Edited and written by rising stars in the field of infectious diseases – authors who have recently taken the boards and excelled, and who understand the challenges posed by this complex field of study and practice.
Download or read book Handbook on Immunosenescence written by Tamas Fulop and published by Springer Science & Business Media. This book was released on 2009-02-27 with total page 1693 pages. Available in PDF, EPUB and Kindle. Book excerpt: This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.
Download or read book Translocator Protein TSPO written by Giovanni Natile and published by MDPI. This book was released on 2018-03-05 with total page 177 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a printed edition of the Special Issue "Translocator Protein (TSPO)" that was published in IJMS
Download or read book Osteogenesis Imperfecta written by Javaid Kassim and published by Academic Press. This book was released on 2013-08-06 with total page 578 pages. Available in PDF, EPUB and Kindle. Book excerpt: Osteogenesis Imperfecta is the first translational reference professionals can turn to for a source of comprehensive information on this disorder. Although several reviews of the field have been published in various journals, there is no other single source for a compendium of current information. Separate chapters discuss each of the several clinical features of OI. Ethical issues related to OI are discussed, as is the importance of nutrition in managing the OI child and the OI adult. The role of physical medicine and rehabilitation for OI patients is also presented, along with the current status of OI medical treatment and the prospects for genetic engineering in the future. The text also provides the orthopedic surgeon with an advanced discussion of surgical techniques applicable to OI. - Incorporates chapters and information on the ethical issues related to osteogenesis imperfecta (OI) as will the importance of nutrition in managing the OI child and the OI adult - Offers new insights into the underlying mechanisms of collagen biochemistry as related to OI as well as a presentation of intracellular collagen processing and the expanded role of protein chaperones in OI - Discusses the role of physical medicine and rehabilitation for OI patients and the current status of OI medical treatment as well as prospects for genetic engineering in the future - Provides a unique overview for the orthopedic surgeon with an advanced discussion of surgical techniques applicable to OI
Download or read book Fat and Skeletal Metastasis written by Guanwu Li and published by Frontiers Media SA. This book was released on 2022-11-03 with total page 110 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Autophagy Cancer Other Pathologies Inflammation Immunity Infection and Aging written by M. A. Hayat and published by Academic Press. This book was released on 2016-12-28 with total page 431 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. - Presents the most advanced information regarding the role of the autophagic system in life and death - Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both - Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation - Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment - Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available
Download or read book Heparanase written by Israel Vlodavsky and published by Springer Nature. This book was released on 2020-04-09 with total page 871 pages. Available in PDF, EPUB and Kindle. Book excerpt: Written by internationally recognized leaders in Heparanase biology, the book’s eight chapters offer an opportunity for scientists, clinicians and advanced students in cell biology, tumor biology and oncology to obtain a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications. Proteases and their involvement in cancer progression have been well addressed and documented; however, the emerging premise presented within this book is that Heparanase is a master regulator of aggressive cancer phenotypes and crosstalk with the tumor microenvironment. This endoglycosidase contributes to tumor-mediated remodeling of the extracellular matrix and cell surfaces, augmenting the bioavailability of pro-tumorigenic and pro-inflammatory growth factors and cytokines that are bound to Heparan sulfate. Compelling evidence ties Heparanase with all steps of tumor progression including tumor initiation, growth, angiogenesis, metastasis, and chemoresistance, supporting the notion that Heparanase is an important contributor to the poor outcome of cancer patients and a validated target for therapy. Unlike Heparanase, heparanase-2, a close homolog of Heparanase, lacks enzymatic activity, inhibits Heparanase, and regulates selected genes that promote normal differentiation and tumor suppression. Written by internationally recognized leaders in Heparanase biology, this volume presents a comprehensive understanding of Heparanase’s multifaceted activities in cancer, inflammation, diabetes and other diseases, as well as its related clinical applications to scientists, clinicians and advanced students in cell biology, tumor biology and oncology.
