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Structural Deterioration of Human Articular Cartilage and Subchondral Plate

Structural Deterioration of Human Articular Cartilage and Subchondral Plate
Author: Neil Chang
Publisher:
Total Pages: 208
Release: 2016
Genre:
ISBN:

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The articular cartilage and underlying subchondral plate, comprised of calcified cartilage and a continuous plate of subchondral bone, form the osteochondral unit which bears and transmits the load as well as maintains low hydraulic conductivity and permeability. Age-related degeneration transitions to osteoarthritis (OA) a disease that results in degeneration of articular cartilage and abnormality of the subchondral plate. The mechanism of this transition is not well known, and likely involves interplay between both the bone and the cartilage. This dissertation aims to delineate the biological and structural changes that occur in the osteochondral interface with age-related degeneration and disease, to help gain a better understanding of the pathogenesis. 3-D morphometric analyses of the subchondral plate in microCT indicated that the tidemark was disrupted and roughened in the early stage of degeneration. Investigating the subchondral plate in histology and with Digital Volumetric Imaging revealed that the disruptions were often caused by penetrating vascular channels that are involved in bone remodeling, which become larger and more abnormal in morphology in early degeneration stages. The penetration and disruption of the tidemark was found to occur in an earlier stage than large changes in the chondrocyte organization and fissuring of the articular cartilage matrix, known hallmarks of OA. Because the disrupted interface can potentially compromise the subchondral plate's ability to act as a barrier to water and solutes, there is the potential of a mechanism where remodeling of the subchondral plate leads to more catabolism and fluid depressurization in the cartilage. These studies provide new technical developments in the ability to analyze three-dimensional datasets computationally, and reduce them to morphometric parameters, allowing a multiscale assessment of the tissue depending on the region of focus and size of targeted objects. They provide quantitative confirmation of known histological hallmarks of degeneration and OA in both the cartilage and subchondral plate. Additionally, they provide novel 3-D information about the structure of the human subchondral plate in degeneration and OA, which has been mostly limited to studies of normal tissue in the past.


Articulation of Human Articular Cartilage Induces Anisotropic Structural Deterioration and Age-Dependent Cellular Responses

Articulation of Human Articular Cartilage Induces Anisotropic Structural Deterioration and Age-Dependent Cellular Responses
Author: Felix Hsu
Publisher:
Total Pages: 173
Release: 2017
Genre:
ISBN:

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Articulation (shear and sliding) has been increasingly studied during the last two decades with the realization of its substantial involvement in daily locomotion of the human knee joint. Conventional biological responses of mechanical stimulation on chondrocyte viability has been studied for shear and sliding; but in addition, the close relationship between articulation and lubrication has emphasized the importance of cell-mediated expression of the key boundary lubricating protein proteoglycan 4 (PRG4). While, in the absent of lubrication, shear and sliding between abnormal congruency between joint surfaces can initiate spatially-varied early degeneration, both instantly by direct mechanical damage of the cartilage and through time by mechanobiology. Thus, the overall motivation of this dissertation was to understand the effect of articulation (shear and sliding) on maintaining joint health as well as causing early or progressed degeneration in human articular cartilage. Spatially-oriented histopathological features were identified in cartilage lesions of human knee medial femoral condyles (MFCs) using a standardized, reliable grading system developed from primary literature, supporting the concept of mechanical articulation-driven cartilage deterioration. To recapitulate in vivo effects of articulation on human articular cartilage, human cartilage explants were subjected to mid to high amplitudes of articulation that can potentially stimulate chondrocyte response and cause matrix damage. Although articulation on cartilage explants induced superficial zone cell death and apoptosis (regardless of aging), only young and not old cartilage responded by secreting higher levels of PRG4 lubricant and continuously expressed enhanced levels of autophagy. However, the articulation regime applied in the absence of lubrication was insufficient to generate noticeable wear at the cartilage surface. Elucidating the mechanobiology of early degeneration in human articular cartilage by assessing the effects of articulation (shear and sliding) on SZ chondrocyte response and the initiation of matrix damage is one step towards a systems-based understanding of synovial joint homeostasis and derangement in health, aging, and disease. Furthermore, understanding the mechanobiological environments that can initiate cartilage degeneration can be critical to the development of preventive therapies for osteoarthritis.


Subchondral Bone Loss and Articular Cartilage Damages in Patients with Knee Osteoarthritis

Subchondral Bone Loss and Articular Cartilage Damages in Patients with Knee Osteoarthritis
Author: Yan Chen
Publisher:
Total Pages:
Release: 2017-01-26
Genre:
ISBN: 9781361033005

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This dissertation, "Subchondral Bone Loss and Articular Cartilage Damages in Patients With Knee Osteoarthritis" by Yan, Chen, 陳炎, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled "Subchondral bone loss and articular cartilage damages in patients with knee osteoarthritis" Submitted by CHEN Yan for the degree of Doctor of Philosophy at the University of Hong Kong in August 2015. Osteoarthritis (OA) is the most prevalent form of arthritis, and characterized by articular cartilage damage and subchondral bone sclerosis. Subchondral bone sclerosis has been demonstrated to lead to cartilage degradation. However, clinical studies showed that treatment of antiresorptive drugs enhance subchondral bone quality, and thus attenuate OA cartilage degeneration. These results suggest a role of subchondral bone loss in OA pathogenesis. Thus, the changes of subchondral bone in OA are still unclear. We aimed to examine subchondral bone changes and their role in human knee OA. Firstly, we examined the effect of risk factors, i.e., hypertension and type 2 diabetes mellitus (T2DM) which are associated with knee OA, and further, with bone loss, on OA subchondral bone. We found significant lower bone mineral density (BMD) and higher porosity at subchondral plate in OA patients with hypertension and T2DM. Furthermore, hypertensive patients had significantly lower bone volume fraction (BV/TV), trabecular number (Tb.N) and higher structure model index (SMI) than non-hypertensive patients. In addition, hypertensive patients showed higher Osteoarthritis Research Society International + (OARSI) score, higher number of Tartrate-resistant acid phosphatase (TRAP) + osteoclasts and lower Osteocalcin osteoblasts. These findings suggest that subchondral bone loss occurs in knee OA patients with hypertension and T2DM, and is associated with exuberated articular cartilage damage. Secondly, because subchondral bone cyst (SBC), a hallmark of OA, is characterized by focal bone loss and surrounding bone sclerosis, we investigated changes in bone and articular cartilage localized in cyst regions in knee OA. We found that cyst group presented higher BV/TV, Tb.N and SMI at subchondral bone than non-cyst group. OARSI score, the numbers of TRAP osteoclasts, + + Osterix osteoprogenitors, Osteocalcin osteoblasts and expression of SOX9, were higher in cyst group. These findings further support the association between subchondral bone loss (associated with SBCs) and articular cartilage damage in knee OA. Finally, to differentiate subchondral bone loss from bone sclerosis, we evaluated subchondral trabecular plate and rod microstructural changes in human OA knees, based on the individual trabecula segmentation technique. We found that in Lateral, Anterior and Posterior subvolumes on lateral condyle, OARSI score, BV/TV, trabecular plate number and volume fraction (pBV/TV), and elastic moduli did not differ between OA and normal control groups. However, OA group had significantly lower trabecular rod number and volume, and increased rod thickness, increased trabecular plate thickness and axial volume fraction, lower plate-plate, plate-rod and rod-rod junction density. These changes occurred similarly in all subvolumes on medial condyle and Medial and Central subvolumes on lateral condyle, excepted that OARSI score, BV/TV, pBV/TV and elastic moduli were higher in OA group. These results suggest that subchondral trabecular rod loss and plate stiffening precedes OA changes in cartilage, and that trabecular rod loss probably precedes trabecular plat


Computational Biomechanics

Computational Biomechanics
Author: Kozaburo Hayashi
Publisher: Springer Science & Business Media
Total Pages: 278
Release: 2012-12-06
Genre: Medical
ISBN: 4431669515

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The combination of readily available computing power and progress in numerical techniques has made nonlinear systems - the kind that only a few years ago were ignored as too complex - open to analysis for the first time. Now realistic models of living systems incorporating the nonlinear variation and anisotropic nature of physical properties can be solved numerically on modern computers to give realistically usable results. This has opened up new and exciting possibilities for the fusing of ideas from physiology and engineering in the burgeoning new field that is biomechanics. Computational Biomechanics presents pioneering work focusing on the areas of orthopedic and circulatory mechanics, using experimental results to confirm or improve the relevant mathematical models and parameters. Together with two companion volumes, Biomechanics: Functional Adaptation and Remodeling and the Data Book on Mechanical Properties of Living Cells, Tissues, and Organs, this monograph will prove invaluable to those working in fields ranging from medical science and clinical medicine to biomedical engineering and applied mechanics.


The Soft–Hard Tissue Junction

The Soft–Hard Tissue Junction
Author: Neil D. Broom
Publisher: Cambridge University Press
Total Pages: 810
Release: 2018-11-29
Genre: Technology & Engineering
ISBN: 1108664768

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Richly illustrated throughout with actual tissue images, this innovative book shows that the soft-hard tissue junction is best understood in a biomechanical context. The authors describe their pioneering experimental methods, providing an essential structure-function framework for computational modelling, and thereby encouraging the development of more realistic, predictive models of this important tissue junction. Covering the three main musculoskeletal junctions of cartilage-bone, disc-vertebra, and ligament/tendon-bone, the relevant soft tissues are examined with respect to both their own inherent structure and their mode of integration with the hard tissue. The soft-hard tissue interface is explored with a focus on structural damage resulting from overloading, and its associated pathologies. Adopting a multiscale approach, ranging in structural resolution from the macro to fibril levels, this is a must-have guide to the field and an ideal resource for researchers seeking new and creative approaches for studying the joint and spine tissues.


Mechanisms of Osteoarthritis

Mechanisms of Osteoarthritis
Author: Geetha Mohan
Publisher:
Total Pages: 492
Release: 2012
Genre: Articular cartilage
ISBN:

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Osteoarthritis (OA) is a progressive joint disease and a common cause of disability. OA is characterised by loss of articular cartilage, subchondral bone sclerosis, cysts, and osteophyte formation. Increased subchondral bone remodelling plays an important role in the pathophysiology of OA and is associated with disease progression. It is known that Osteoprotegerin (OPG), receptor activator of nuclear factor kappa b (RANK) and its ligand RANKL tightly control bone remodelling. In addition, RANK, RANKL and OPG gene expression has been shown to be dysregulated in human OA subchondral bone. Commonly OA is diagnosed at advanced stages, which makes it difficult to study the initiating events in the human disease. Animal models of OA are of considerable importance to study the progressive changes in OA, and to evaluate suitable OA drugs. Alendronate (ALN) is a potent bone resorption inhibitor and clinical trials using bisphosphonates to treat OA have yielded mixed results. This suggests that the effects of bisphosphonates may or may not be beneficial depending on the stage of OA progression. The first aim of this thesis was to characterise the temporal structural changes of tibial articular cartilage and subchondral bone in a low-dose MIA-induced OA rat model. The results from micro-CT analysis showed that the tibiae of the MIA-injected knees had significant bone loss at 2 weeks (early OA), followed by increased bone volume, trabecular thickness and separation at 6 weeks (intermediate OA) and 10 weeks (advanced OA). Micro-CT images revealed subchondral bone sclerosis, cysts, and osteophyte formation at 6 and 10 weeks. Histology revealed progressive cartilage degradation characteristic of the human disease. The second aim of this thesis was to study the effect of ALN treatment initiated at day 0 (pre-emptive), week 2 (early treatment), and week 6 (delayed treatment) in a low-dose MIA rat model. To address the second aim the efficacy of ALN was tested on cartilage degradation, subchondral bone remodelling, and joint discomfort observed in this animal model. The study demonstrated that pre-emptive ALN treatment preserved subchondral trabecular bone microarchitecture, decreased bone turnover, prevented joint discomfort, and offered moderate chondroprotection. Early and delayed ALN treatment prevented loss of trabeculae and decreased bone turnover but did not have any identified effect on cartilage. Finally, the RANK, RANKL, OPG gene expression in OA was characterised in a lowdose MIA rat model. The effect of ALN treatment on subchondral bone RANK, RANKL, and OPG gene expression at 2, 6, and 10 weeks after OA induction was assessed. This study showed that the RANKL and OPG gene expression was dysregulated in this animal model. In addition, the efficacy of ALN on early subchondral bone changes appears to occur through the modulation of RANKL and OPG gene expression. Collectively, these findings demonstrate that the low-dose MIA rat model closely mimics the pathological features of progressive human OA disease. Moreover, this animal model showed a clear relationship between the cartilage damage and subchondral bone changes. ALN treatment preserved subchondral trabecular bone microarchitecture and decreased bone turnover. In addition, ALN prevented RANKL and OPG gene dysregulation in OA subchondral bone. Normalising subchondral bone remodelling offers an optimal treatment option and future drug intervention studies focusing on subchondral bone would provide improved treatment options for OA.


Diagnostic and Surgical Arthroscopy in the Horse - E-Book

Diagnostic and Surgical Arthroscopy in the Horse - E-Book
Author: C. Wayne McIlwraith
Publisher: Elsevier Health Sciences
Total Pages: 464
Release: 2014-06-27
Genre: Medical
ISBN: 072343817X

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From the worldwide leader in equine surgery, Wayne McIlwraith, comes the new fourth edition of Diagnostic and Surgical Arthroscopy in the Horse. Completely revised and expanded, this comprehensive atlas covers all the need-to-know information within equine arthroscopy: instrumentation, general techniques, carpal joints, metacarpal and metatarsophalangeal joints, and tarsocrural joints. All the advances that have taken place in the field over the last decade are covered, particularly in the areas of postoperative management and rehabilitation. This trusted reference also provides an in-depth view of surgical procedures with new high-definition diagnostic and surgical arthroscopic images, as well as radiographs and composite illustrations. There is no better way to learn and master equine surgical procedures! Diagnostic images with side-by-side radiographs and illustrations offer multiple points of view and directional guidance on surgical procedures. Expert authorship features helpful insights and expertise from the worldwide leader and speaker on equine arthoscopy, Wayne McIlwraith. Specially commissioned artwork clearly illustrates local anatomy and key stages of surgical procedures. Coverage of choice, use, and maintenance of equipment provides a basic understanding of arthroscopic technique and reasoning behind various practices. Content dedicated to diagnostic and surgical arthroscopy of the horse provides authoritative, comprehensive information on this specialized subject. NEW! Updated high-definition images provide a crystal clear view of surgical procedures from multiple views. NEW! Companion website features 48 high-resolution digital videos that link back to the textbook for a vivid demonstration of surgical techniques. NEW! Expanded content ensures you are up to date on the latest developments in the field — particularly in the areas of tenoscopy, bursoscopy, and arthroscopic methods for cartilage repair. NEW! Chapter on postoperative management, adjunctive therapies, and rehabilitation procedures keeps you abreast of best practices when it comes to taking care of the horse post-operation.


Biomarkers in Bone Disease

Biomarkers in Bone Disease
Author: Victor R. Preedy
Publisher: Springer
Total Pages: 0
Release: 2017-07-14
Genre: Medical
ISBN: 9789400776920

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In the past decade there has been a major sea change in the way disease is diagnosed and investigated due to the advent of high throughput technologies, such as microarrays, lab on a chip, proteomics, genomics, lipomics, metabolomics etc. These advances have enabled the discovery of new and novel markers of disease relating to autoimmune disorders, cancers, endocrine diseases, genetic disorders, sensory damage, intestinal diseases etc. In many instances these developments have gone hand in hand with the discovery of biomarkers elucidated via traditional or conventional methods, such as histopathology or clinical biochemistry. Together with microprocessor-based data analysis, advanced statistics and bioinformatics these markers have been used to identify individuals with active disease or pathology as well as those who are refractory or have distinguishing pathologies. New analytical methods that have been used to identify markers of disease and is suggested that there may be as many as 40 different platforms. Unfortunately techniques and methods have not been readily transferable to other disease states and sometimes diagnosis still relies on single analytes rather than a cohort of markers. There is thus a demand for a comprehensive and focused evidenced-based text and scientific literature that addresses these issues. Hence the formulation of Biomarkers in Disease. The series covers a wide number of areas including for example, nutrition, cancer, endocrinology, cardiology, addictions, immunology, birth defects, genetics, and so on. The chapters are written by national or international experts and specialists.


Animal Models in Orthopaedic Research

Animal Models in Orthopaedic Research
Author: Yuehuei H. An
Publisher: CRC Press
Total Pages: 619
Release: 2020-04-30
Genre: Medical
ISBN: 1482234025

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Animal Models in Orthopaedic Research is a reference book of the major animal models used in the study of orthopaedic conditions and in the in vivo study of biomaterials. Use of animal models provides important knowledge about pathological conditions that can eventually lead to the development of more effective clinical treatment of diseases in bot


Osteoarthritis

Osteoarthritis
Author: Roland W. Moskowitz
Publisher: Lippincott Williams & Wilkins
Total Pages: 492
Release: 2007
Genre: Medical
ISBN: 9780781767071

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Written by the foremost experts, this text is a comprehensive clinical reference on osteoarthritis. Chapters review current information on the epidemiology, etiopathogenesis, and pathology of osteoarthritis, the biochemistry and molecular and cell biology of articular cartilage, and experimental models of osteoarthritis. Major sections focus on clinical presentations, roentgenologic and laboratory diagnosis, and treatment, including pharmacologic treatment, intra-articular therapy, surgery, arthroscopy, and complementary and alternative medicine. The authors discuss the indications, outcomes, and complications of various orthopaedic procedures. Chapters present orthopaedic approaches to osteoarthritis of various joints—the shoulder, hand, wrist, elbow, hip, knee, foot, ankle, and cervical, thoracic, and lumbar spine.