Acidosis, a Fundamental Regulator of Bone Cell Function PDF Download

Author: Michelle Laura Key
Publisher:
ISBN:
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Languages : en
Pages : 0

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Author: M. L. Key
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Previous work has demonstrated that bone cells are highly sensitive to extracellular acidification. Low pH is a key osteoclast activation factor, and reduces bone formation by inhibiting mineralisation of the matrix. The aim of this thesis was to investigate further the roles played by pH in modulating bone cell function. Transient receptor potential (TRP) channels detect protons within the pathophysiological range, so are potential candidates for mediating the observed effects of acid on bone cells. I found that TRPV1 agonists/antagonists had no effect on osteoclast formation and activation or bone mineralisation by osteoblasts. Additionally, TRPV1-/- osteoclasts demonstrated no functional differences from wildtypes. Furthermore, agonists/antagonists for TRPM8, TRPV4 and TRPV3 were without effect. Pyrophosphate (PPi) a fundamental inhibitor of mineralisation in the bone microenvironment is generated from extracellular nucleotides by ecto-nucleotidases such as E-NPP1. I showed that E-NPP1 mRNA and protein were up-regulated in osteoblasts cultured at pH 6.9; total E-NPP activity was also increased. To determine the role of acidification in tumour-induced osteolysis, I devised an in vitro model to investigate interactions of osteoclasts with breast cancer cells, which metastasise to bone, sometimes causing osteolytic disease. Surprisingly, the overall effect of breast cancer cells on osteoclasts was inhibitory; however, resorption was significantly stimulated relative to buffered controls when breast cancer cells were allowed to acidify the culture medium. These results suggest that local acidification in tumour settings in vivo could be an important factor in determining the degree of osteolysis that occurs. Finally, I investigated whether two key cytokines implicated in the vicious cycle model of tumour-mediated osteolysis, B-cell activating factor (BAFF) and activin A influence osteoclast function. In all experiments only acidosis stimulated osteoclast resorption. These results provide further evidence for the fundamental role of acid as a regulator of bone cell function.

Author:
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ISBN:
Category :
Languages : en
Pages : 362

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Author: Robert Marcus
Publisher: Academic Press
ISBN: 0123982529
Category : Medical
Languages : en
Pages : 2140

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Now in its fourth edition, Osteoporosis is a classic reference on this disease, comprising a tremendous wealth of knowledge in a single source not found elsewhere. Written by renowned experts in the field, this two-volume work is a must-have for academic and medical libraries, physicians, researchers, and any company involved in osteoporosis research and development. This newest edition covers everything from basic anatomy and physiology to diagnosis, management and treatment in which direct care costs for osteoporotic fractures in the United States reach up to $18 billion each year. Worldwide, 200 million women ages 60 to 80 suffer from osteoporosis and have a lifetime risk of fracture between 30% and 40%, continuing to make osteoporosis a critical challenge in medicine. - Recognizes the critical importance of the Wnt signaling pathway for bone health - Incorporates new chapters on osteocytes, phosphatonins, mouse genetics, and CNS and bone - Examines essential updates on estrogen prevention and treatment and the recent results from the WHO - Discusses the controversial topics of screening and clinical trial design for drug registration - Includes essential updates on therapeutic uses of calcium, vitamin D, SERMS, bisphosphonates, and parathyroid hormone - Offers critical reviews of reproductive and hormonal risk factors, ethnicity, nutrition, therapeutics, management, and economics

Author: Erik Fink Eriksen
Publisher: Lippincott Williams & Wilkins
ISBN: 9780781701228
Category : Bone Diseases, Metabolic
Languages : en
Pages : 0

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Author: Shaul Massry
Publisher: Springer Science & Business Media
ISBN: 1461342171
Category : Medical
Languages : en
Pages : 611

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We present to our readers the proceedings of the Second International Workshop on Phosphate. A short account of the history of the effort led to the Phosphate Workshops is appro priate and can be of interest to the reader. The idea for Phosphate Workshops was born in the early days of November, 1974. One of us (S. G. M. ) suggested the thought to a group of scientists gathered for a luncheon in one of the attrac tive small restaurants in Weisbaden, Germany. The purpose of the workshop was to bring together interested scientists to discuss the newer developments and the recent advances in the field of phosphate metabolism and the other related minerals. An Organizing Committee made of Shaul G. Massry (USA), Louis V. Avioli (USA), Philippe Bordier (France), Herbert Fleisch (Switzerland), and Eduardo Slatopolsky (USA) was formed. The First Workshop was held in Paris during June 5-6, 1975 and was hosted by Dr. Philippe Bordier. Its proceeding was already published. The Second Workshop took place in Heidelberg during June 28-30, 1976 and was hosted by Dr. Eberhard Ritz. Both of these workshops were extremely successful scientific endeavors, and the need for them was demonstrated by the great interest they generated among the scientific community. The Or ganizing Committee, therefore, decided to continue with the tradi tion to hold additional Workshops annually or every other year.

Author: David W. Dempster
Publisher: Academic Press
ISBN: 0128130741
Category : Science
Languages : en
Pages : 1950

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Marcus and Feldman's Osteoporosis, Fifth Edition, is the most comprehensive, authoritative reference on this disease. Led by a new editorial team, this fifth edition offers critical information on reproductive and hormonal risk factors, new therapeutics, ethnicity, nutrition, therapeutics, management and economics, comprising a tremendous wealth of knowledge in a single source not found elsewhere. Written by renowned experts in the field, this two-volume reference is a must-have for biomedical researchers, research clinicians, fellows, academic and medical libraries, and any company involved in osteoporosis drug research and development. - Summarizes the latest research in bone biology and translational applications in a range of new therapeutic agents, including essential updates on therapeutic uses of calcium, vitamin D, SERMS, bisphosphonates, parathyroid hormone, and new therapeutic agents - Recognizes the critical importance of new signaling pathways for bone health, including Wnt, OPG and RANK, of interest to both researchers who study bone biology and clinicians who treat osteoporosis - Offers new insights into osteoporosis associated with menopause, pre-menopause, chronic kidney disease, diabetes, HIV and other immune disorders

Author: Ronald P. Rubin
Publisher: CRC Press
ISBN: 1000153592
Category : Science
Languages : en
Pages : 168

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Lipid Second Messengers provides detailed methodology for analysis of various lipid signaling pathways. Authoritative contributors explain the factors that regulate lipid second messenger production by agonist-activated enzymes and examine their products. Topics discussed include procedures used to measure lipid-derived mediators such as lysophospholipids, arachidonic acid, eicosanoids, anandamide, and ceramides, and the enzymes responsible for generating these messengers, such as phospholipases, prostaglandin endoperoxide synthases, and sphingomyelinase.

Author: J. Gordon Betts
Publisher:
ISBN: 9781947172807
Category :
Languages : en
Pages : 0

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Author: John P. Bilezikian
Publisher: Academic Press
ISBN: 0080568750
Category : Medical
Languages : en
Pages : 2074

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Principles of Bone Biology provides the most comprehensive, authoritative reference on the study of bone biology and related diseases. It is the essential resource for anyone involved in the study of bone biology. Bone research in recent years has generated enormous attention, mainly because of the broad public health implications of osteoporosis and related bone disorders. - Provides a "one-stop" shop. There is no need to search through many research journals or books to glean the information one wants...it is all in one source written by the experts in the field - The essential resource for anyone involved in the study of bones and bone diseases - Takes the reader from the basic elements of fundamental research to the most sophisticated concepts in therapeutics - Readers can easily search and locate information quickly as it will be online with this new edition