Bone Formation and Development

Au0586 half title page 11/17/05 2:05 PM Page 1 EMBEDDEDLINUX SYSTEMDESIGN ANDDEVELOPMENT TEAM FLYAu0586 title page 11/17/05 2:04 PM Page 1 Boca Raton New YorkEMBEDDEDLINUX SYSTEMDESIGN ANDDEVELOPMENTP. Raghavan • Amol Lad • Sriram Neelakandan Published in 2006 byAuerbach Publications Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300Boca Raton, FL 33487-2742© 2006 by Taylor & Francis Group, LLCAuerbach is an imprint of Taylor & Francis GroupNo claim to original U.S. Government worksPrinted in the United States of America on acid-free paper10987654321International Standard Book Number-10: 0-8493-4058-6 (Hardcover) International Standard Book Number-13: 978-0-8493-4058-1 (Hardcover) Library of Congress Card Number 2005048179This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted withpermission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publishreliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materialsor for the consequences of their use.No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, orother means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any informationstorage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com(http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. Fororganizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged.Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only foridentification and explanation without intent to infringe.Library of Congress Cataloging-in-Publication DataRaghavan, P. (Pichai), 1973-embedded linux system design and development pdf' title='embedded linux system design and development pdf'>Embedded Linux System Design and Development Ⅲ Borland is a registered trademark of Borland Software Corporation in the United States and other countries. Ⅲ Merant is a registered trademark of Merant. Ⅲ SnapGear is a registered trademark of SnapGear Inc. Ⅲ Matsushita is a trademark of the Matsushita Electric Corporation. Ⅲ I2C is a trademark of Philips Semiconductors Corporation. Ⅲ Philips® is a registered trademark of Philips Consumer Electronics Corporation. Ⅲ Cadenux is a trademark of Cadenux, LLC. Ⅲ ELinOS is a registered trademark of SYSGO AG. Ⅲ Metrowerks and CodeWarrior are trademarks of Metrowerks Corp. in the U.S. or other countries. Ⅲ FreeBSD is a registered trademark of the FreeBSD Foundation. Ⅲ IEEE and POSIX are registered trademarks of Institute of Electrical and Electronics Engineers, Inc. in the United States. Ⅲ Xtensa is a trademark belonging to Tensilica Inc. Ⅲ Fujitsu is a registered trademark of Fujitsu, Ltd. Ⅲ Firewire is a registered trademark of Apple computer. Ⅲ SuperH is a trademark of Hitachi, Ltd. Ⅲ Windows, WinCE and Microsoft are registered trademarks and MS-DOS and DirectX .are trademarks of Microsoft Corporation. Ⅲ Solaris and Java are registered trademarks and Bone Formation and Development Bone Formation and Development Bởi: OpenStaxCollege In the early stages of embryonic development, the embryo’s skeleton consists of fibrous membranes and hyaline cartilage By the sixth or seventh week of embryonic life, the actual process of bone development, ossification (osteogenesis), begins There are two osteogenic pathways—intramembranous ossification and endochondral ossification—but bone is the same regardless of the pathway that produces it Cartilage Templates Bone is a replacement tissue; that is, it uses a model tissue on which to lay down its mineral matrix For skeletal development, the most common template is cartilage During fetal development, a framework is laid down that determines where bones will form This framework is a flexible, semi-solid matrix produced by chondroblasts and consists of hyaluronic acid, chondroitin sulfate, collagen fibers, and water As the matrix surrounds and isolates chondroblasts, they are called chondrocytes Unlike most connective tissues, cartilage is avascular, meaning that it has no blood vessels supplying nutrients and removing metabolic wastes All of these functions are carried on by diffusion through the matrix This is why damaged cartilage does not repair itself as readily as most tissues Throughout fetal development and into childhood growth and development, bone forms on the cartilaginous matrix By the time a fetus is born, most of the cartilage has been replaced with bone Some additional cartilage will be replaced throughout childhood, and some cartilage remains in the adult skeleton Intramembranous Ossification During intramembranous ossification, compact and spongy bone develops directly from sheets of mesenchymal (undifferentiated) connective tissue The flat bones of the face, most of the cranial bones, and the clavicles (collarbones) are formed via intramembranous ossification 1/11 Bone Formation and Development The process begins when mesenchymal cells in the embryonic skeleton gather together and begin to differentiate into specialized cells ([link]a) Some of these cells will differentiate into capillaries, while others will become osteogenic cells and then osteoblasts Although they will ultimately be spread out by the formation of bone tissue, early osteoblasts appear in a cluster called an ossification center The osteoblasts secrete osteoid, uncalcified matrix, which calcifies (hardens) within a few days as mineral salts are deposited on it, thereby entrapping the osteoblasts within Once entrapped, the osteoblasts become osteocytes ([link]b) As osteoblasts transform into osteocytes, osteogenic cells in the surrounding connective tissue differentiate into new osteoblasts Osteoid (unmineralized bone matrix) secreted around the capillaries results in a trabecular matrix, while osteoblasts on the surface of the spongy bone become the periosteum ([link]c) The periosteum then creates a protective layer of compact bone superficial to the trabecular bone The trabecular bone crowds nearby blood vessels, which eventually condense into red marrow ([link]d) Intramembranous Ossification Intramembranous ossification follows four steps (a) Mesenchymal cells group into clusters, and ossification centers form (b) Secreted osteoid traps osteoblasts, which then become osteocytes (c) Trabecular matrix and periosteum form (d) Compact bone develops superficial to the trabecular bone, and crowded blood vessels condense into red marrow 2/11 Bone Formation and Development Intramembranous ossification begins in utero during fetal development and continues on into adolescence At birth, the skull and clavicles are not fully ossified nor are the sutures of the skull closed This allows the skull and shoulders to deform during passage through the birth canal The last bones to ossify via intramembranous ossification are the flat bones of the face, which reach their adult size at the end of the adolescent growth spurt Endochondral Ossification In endochondral ossification, bone develops by replacing hyaline cartilage Cartilage does not become bone Instead, cartilage serves as a template to be completely replaced by new bone Endochondral ossification takes much longer than intramembranous ossification Bones at the base of the skull and long bones form via endochondral ossification In a long bone, for example, at about to weeks after conception, some of the mesenchymal cells differentiate into chondrocytes (cartilage cells) that form the cartilaginous skeletal precursor of the bones ([link]a) Soon after, the perichondrium, a membrane that covers the cartilage, appears [link]b) 3/11 Bone Formation and Development Endochondral Ossification Endochondral ossification follows five steps (a) Mesenchymal cells differentiate into chondrocytes (b) The cartilage model of the future bony skeleton and the perichondrium form (c) Capillaries penetrate cartilage Perichondrium transforms into periosteum Periosteal collar develops Primary ossification center develops ... Au0586 half title page 11/17/05 2:05 PM Page 1 EMBEDDEDLINUX SYSTEMDESIGN ANDDEVELOPMENT TEAM FLYAu0586 title page 11/17/05 2:04 PM Page 1 Boca Raton New YorkEMBEDDEDLINUX SYSTEMDESIGN ANDDEVELOPMENTP. Raghavan • Amol Lad • Sriram Neelakandan Published in 2006 byAuerbach Publications Taylor & Francis Group 6000 Broken Sound Parkway NW, Suite 300Boca Raton, FL 33487-2742© 2006 by Taylor & Francis Group, LLCAuerbach is an imprint of Taylor & Francis GroupNo claim to original U.S. Government worksPrinted in the United States of America on acid-free paper10987654321International Standard Book Number-10: 0-8493-4058-6 (Hardcover) International Standard Book Number-13: 978-0-8493-4058-1 (Hardcover) Library of Congress Card Number 2005048179This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted withpermission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made to publishreliable data and information, but the author and the publisher cannot assume responsibility for the validity of all materialsor for the consequences of their use.No part of this book may be reprinted, reproduced, transmitted, or utilized in any form by any electronic, mechanical, orother means, now known or hereafter invented, including photocopying, microfilming, and recording, or in any informationstorage or retrieval system, without written permission from the publishers. For permission to photocopy or use material electronically from this work, please access www.copyright.com(http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC) 222 Rosewood Drive, Danvers, MA01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of users. Fororganizations that have been granted a photocopy license by the CCC, a separate system of payment has been arranged.Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only foridentification and explanation without intent to infringe.Library of Congress Cataloging-in-Publication DataRaghavan, P. (Pichai), 1973-Embedded Linux system design and development / P. Raghavan, Amol Lad, Sriram Neelakandan.p. cm.Includes bibliographical references and index.ISBN 0-8493-4058-6 (alk. paper)1. Linux. 2. Operating systems (Computers) 3. Embedded computer systems. I. Lad, Amol. II. Neelakandan, Sriram. III. Title.QA76.76.O63R335 2005005.4'32--dc22 2005048179Visit the Taylor & Francis Web site at http://www.taylorandfrancis.comand the Auerbach Publications Web site at http://www.auerbach-publications.comTaylor & Francis Group is the Academic Division of T&F Informa plc. All source code in the book is released under GNU GPL v2. It can be used as desired under terms andconditions of GNU GPL v2. Trademarks Ⅲ MIPS is a registered trademark and YAMON is a trademark of MIPS Technologies. Ⅲ IBM and ClearCase are registered trademarks and PowerPC is a trademark of International Business Machines Corporation. Ⅲ UNIX is a registered trademark in the United States and other countries, licensed exclusively through X/Open Company Limited. Ⅲ X11 is a trademark of Massachusetts Institute of Technology. Ⅲ NEC is a registered trademark of NEC Corporation Ⅲ HP is a registered trademark of Hewlett-Packard Company. Ⅲ ColdFire is a registered trademark and Motorola is a trademark of Motorola, Inc Ⅲ Microblaze is trademark of Xilinx Inc Ⅲ Red Hat is a registered trademark Introduction toRisk Management05/15/96 Introduction to RiskManagementWarningThis workbook is the product of, and copy-righted by, Citicorp North America, Inc. It issolely for the internal use of Citicorp NorthAmerica, Inc., and may not be used for anyother purpose. It is unlawful to reproduce thecontents of these materials, in whole or in part,by any method, printed, electronic, orotherwise; or to disseminate or sell the samewithout the prior written consent of Trainingand Development Centers - Asia Pacific /CEEMEA / Latin America.Please sign your name in the space below. Table of Contents v05/15/96 Version 2.0p01/07/00Table of ContentsINTRODUCTION Introduction: Risk Management Module .viiOverview . viiIntroduction to Risk Management .xiOverview xiObjectives . xiTopics . xiiThe Workbook Open Access Available online http://arthritis-research.com/content/10/5/R104 Page 1 of 7 (page number not for citation purposes) Vol 10 No 5 Research article The relationship between inflammation and new bone formation in patients with ankylosing spondylitis Xenofon Baraliakos 1 , Joachim Listing 2 , Martin Rudwaleit 3 , Joachim Sieper 3 and Juergen Braun 1 1 Rheumazentrum Ruhrgebiet Herne, Ruhr-University Bochum, Landgrafenstr. 15, 44652 Herne, Germany 2 German Rheumatism Research Center, Charitéplatz 1, 10117 Berlin, Germany 3 Rheumatology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany Corresponding author: Juergen Braun, j.braun@rheumazentrum-ruhrgebiet.de Received: 2 May 2008 Revisions requested: 4 Jul 2008 Revisions received: 23 Jul 2008 Accepted: 1 Sep 2008 Published: 1 Sep 2008 Arthritis Research & Therapy 2008, 10:R104 (doi:10.1186/ar2496) This article is online at: http://arthritis-research.com/content/10/5/R104 © 2008 Baraliakos et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Spinal inflammation as detected by magnetic resonance imaging and new bone formation as identified by conventional radiographs are characteristic of ankylosing spondylitis. Whether and how spondylitis and syndesmophyte formation are linked are unclear. Our objective was to investigate whether and how spinal inflammation are associated with new bone formation in ankylosing spondylitis. Methods Spinal magnetic resonance images and conventional radiographs from 39 ankylosing spondylitis patients treated with anti-tumour necrosis factor (anti-TNF) agents at baseline and after 2 years were analysed for syndesmophyte formation at vertebral edges with or without inflammatory lesions at baseline. Results Overall, 922 vertebral edges at the cervical and lumbar spine were analysed. At baseline, the proportion of vertebral edges with and without inflammation (magnetic resonance imaging) that showed structural changes (conventional radiographs) was similar (in total, 16.6% of all vertebral edges in 71.4% of patients). From the perspective of syndesmophyte formation (n = 26, 2.9%) after 2 years, there were more vertebral edges without (62%) than with (38%) inflammation at baseline (P = 0.03). From the perspective of spinal inflammation at baseline (n = 153 vertebral edges), more syndesmophytes developed at vertebral edges with (6.5%) than without (2.1%) inflammation (P = 0.002, odds ratio 3.3, 95% confidence interval 1.5 to 7.4). Inflammation persisted in 31% of the initially inflamed vertebral edges (n = 132), and new lesions developed in 8% of the vertebral edges without inflammation at baseline (n = 410). From the perspective of spinal inflammation after 2 years (n = 72 vertebral edges), 5.6% of the vertebral edges showed syndesmophyte development in contrast to 1.9% of the vertebral edges with new syndesmophytes without inflammation (P = 0.06). Conclusions These findings obtained in patients treated with anti-TNF agents suggest linkage and some dissociation of inflammation and new bone formation in ankylosing spondylitis. Although syndesmophytes were also found to develop at sites where no inflammation had been seen by magnetic resonance imaging at baseline, it was more likely that syndesmophytes developed in inflamed vertebral edges. More effective suppression of spinal inflammation may be required to inhibit structural damage in ankylosing spondylitis. Introduction Ankylosing spondylitis (AS) is a frequent chronic inflammatory rheumatic disease that already affects the axial skeleton at a young age [1], starting in the sacroiliac joints and later spread- ing to the spine [2]. Active inflammatory spinal lesions as detected by magnetic Open Access Available online http://arthritis-research.com/content/10/5/R125 Page 1 of 8 (page number not for citation purposes) Vol 10 No 5 Research article Serum levels of biomarkers of bone and cartilage destruction and new bone formation in different cohorts of patients with axial spondyloarthritis with and without tumor necrosis factor-alpha blocker treatment Heiner Appel 1 , Louise Janssen 1 , Joachim Listing 2 , René Heydrich 1 , Martin Rudwaleit 1 and Joachim Sieper 1,2 1 Department of Gastroenterology, Infectiology and Rheumatology, Charité Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany 2 Deutsches Rheumaforschungszentrum Berlin, Schumannstrassse 21/22, 10117 Berlin, Germany Corresponding author: Heiner Appel, heiner.appel@charite.de Received: 7 Aug 2008 Revisions requested: 8 Sep 2008 Revisions received: 8 Oct 2008 Accepted: 22 Oct 2008 Published: 22 Oct 2008 Arthritis Research & Therapy 2008, 10:R125 (doi:10.1186/ar2537) This article is online at: http://arthritis-research.com/content/10/5/R125 © 2008 Appel et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Introduction Recent data about radiographic progression during treatment with tumor necrosis factor-alpha (TNF-α) blocker agents in patients with ankylosing spondylitis (AS) have prompted an intensive discussion about the link between inflammation/bone destruction and new bone formation and the order of events. Therefore, we analysed parameters of cartilage degradation, neoangiogenesis, and new bone formation in different cohorts of patients with axial spondyloarthritis with and without treatment with TNF-α blocker agents. Method TNF-α blocker-naïve AS patients were investigated for serum levels of metalloproteinase-3 (MMP-3) (n = 71), vasoendothelial growth factor (VEGF) (n = 50), and bone- specific alkaline phosphatase (BALP) (n = 71) at baseline and after 1 and 2 years. This was compared with 34 adalimumab- treated patients with axial spondyloarthritis (22 AS and 12 non- radiographic axial spondyloarthritis patients) before and after 36 to 52 weeks of treatment. Results There were no significant changes in serum levels of MMP-3 (P > 0.05), VEGF (P > 0.05), and BALP (P > 0.05) in a large cohort of TNF-α blocker-naïve AS patients followed for 2 years. In contrast, adalimumab-treated spondyloarthritis (AS and non-radiographic axial spondyloarthritis) patients had a significant decrease of VEGF (P < 0.001) and MMP-3 (P = 0.022) after 36 to 52 weeks of therapy. Most interestingly, the level of BALP increased significantly after 36 to 52 weeks of therapy (P < 0.001). A decrease in MMP-3 serum levels correlated significantly to an increase of BALP (r = -0.398, P = 0.02). In the case of VEGF, there was a negative correlation without significance (r = -0.214, P > 0.05). Conclusions Rising levels of BALP and the negative correlation between MMP-3 and BALP in spondyloarthritis patients with TNF-α blocker treatment indicate that new bone formation in AS occurs if inflammation is successfully treated and might be part of a healing process. Introduction Ankylosing spondylitis (AS) is a chronic inflammatory disease with inflammation in the spine which can lead to bone ero- sions, new bone formation, and ankylosis in the spine. Inflam- mation is partly mediated by tumor necrosis factor-alpha (TNF- α) [1]. Treatment of patients with active AS with the currently approved TNF-blocking agents infliximab [2], etanercept [3], and adalimumab [4] has been shown to be highly effective for the improvement of signs, symptoms, and function and the reduction of both C-reactive protein (CRP) and active inflam- mation in the sacroiliac joints and the spine as shown by ... known to weaken bones, and extra body weight puts additional stress on the bones Watch this video to see how a bone grows 8/11 Bone Formation and Development Chapter Review All bone formation is... flat bones of the face, most of the cranial bones, and a good deal of the clavicles (collarbones) are formed 10/11 Bone Formation and Development via intramembranous ossification, while bones... the trabecular bone, and crowded blood vessels condense into red marrow 2/11 Bone Formation and Development Intramembranous ossification begins in utero during fetal development and continues