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Matrix Biology : Journal of the... Oct 2018Hyaline cartilages, fibrocartilages and elastic cartilages play multiple roles in the human body including bearing loads in articular joints and intervertebral discs,... (Review)
Review
Hyaline cartilages, fibrocartilages and elastic cartilages play multiple roles in the human body including bearing loads in articular joints and intervertebral discs, providing joint lubrication, forming the external ears and nose, supporting the trachea, and forming the long bones during development and growth. The structure and organization of cartilage's extracellular matrix (ECM) are the primary determinants of normal function. Most diseases involving cartilage lead to dramatic changes in the ECM which can govern disease progression (e.g., in osteoarthritis), cause the main symptoms of the disease (e.g., dwarfism caused by genetically inherited mutations) or occur as collateral damage in pathological processes occurring in other nearby tissues (e.g., osteochondritis dissecans and inflammatory arthropathies). Challenges associated with cartilage diseases include poor understanding of the etiology and pathogenesis, delayed diagnoses due to the aneural nature of the tissue and drug delivery challenges due to the avascular nature of adult cartilages. This narrative review provides an overview of the clinical and pathological features as well as current treatment options available for various cartilage diseases. Late breaking advances are also described in the quest for development and delivery of effective disease modifying drugs for cartilage diseases including osteoarthritis, the most common form of arthritis that affects hundreds of millions of people worldwide.
Topics: Cartilage Diseases; Cartilage, Articular; Disease Progression; Extracellular Matrix; Humans; Mutation
PubMed: 29803938
DOI: 10.1016/j.matbio.2018.05.005 -
Journal of Bone and Mineral Research :... Feb 2019Phenotypic variation in skeletal traits and diseases is the product of genetic and environmental factors. Epigenetic mechanisms include information-containing factors,... (Review)
Review
Phenotypic variation in skeletal traits and diseases is the product of genetic and environmental factors. Epigenetic mechanisms include information-containing factors, other than DNA sequence, that cause stable changes in gene expression and are maintained during cell divisions. They represent a link between environmental influences, genome features, and the resulting phenotype. The main epigenetic factors are DNA methylation, posttranslational changes of histones, and higher-order chromatin structure. Sometimes non-coding RNAs, such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are also included in the broad term of epigenetic factors. There is rapidly expanding experimental evidence for a role of epigenetic factors in the differentiation of bone cells and the pathogenesis of skeletal disorders, such as osteoporosis and osteoarthritis. However, different from genetic factors, epigenetic signatures are cell- and tissue-specific and can change with time. Thus, elucidating their role has particular difficulties, especially in human studies. Nevertheless, epigenomewide association studies are beginning to disclose some disease-specific patterns that help to understand skeletal cell biology and may lead to development of new epigenetic-based biomarkers, as well as new drug targets useful for treating diffuse and localized disorders. Here we provide an overview and update of recent advances on the role of epigenomics in bone and cartilage diseases. © 2019 American Society for Bone and Mineral Research.
Topics: Animals; Cartilage Diseases; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans; MicroRNAs; RNA, Long Noncoding
PubMed: 30715766
DOI: 10.1002/jbmr.3662 -
Arthritis & Rheumatology (Hoboken, N.J.) Jul 2017
Review
Topics: Arthroscopy; Cartilage Diseases; Cartilage, Articular; Chondrocytes; Humans; Tissue Scaffolds
PubMed: 28294573
DOI: 10.1002/art.40094 -
Instructional Course Lectures 2021Chondral lesions of the patellofemoral joint are common, and when symptomatic they can be difficult to manage. Not only are there various degrees of injury with multiple...
Chondral lesions of the patellofemoral joint are common, and when symptomatic they can be difficult to manage. Not only are there various degrees of injury with multiple etiologies, but patellofemoral anatomy is complex and the patient's lower extremity alignment may contribute to the pathology. Treatment depends on the location, size, and depth of the lesion and may require realignment or concomitant stabilizing procedures. Tibial tubercle osteotomy can be performed in isolation or combined with various cartilage-based treatments, including marrow stimulation techniques, autologous chondrocyte implantation, osteochondral autograft, and osteochondral allograft. End-stage lesions, failed primary patellofemoral cartilage restoration with diffuse involvement, or isolated primary patellofemoral arthritis may be amenable to treatment with patellofemoral arthroplasty. Recent investigations in properly indicated patients using advanced techniques have shown that management of patellofemoral cartilage disease is now more effective and predictable than in the past.
Topics: Cartilage Diseases; Cartilage, Articular; Humans; Joint Diseases; Osteotomy; Patellofemoral Joint; Tibia
PubMed: 33438917
DOI: No ID Found -
Investigative Radiology Oct 2000Cartilage degenerative diseases affect millions of people. Our understanding of these diseases and our ability to establish efficacious treatment strategies have been... (Review)
Review
Cartilage degenerative diseases affect millions of people. Our understanding of these diseases and our ability to establish efficacious treatment strategies have been confounded by the difficulty of nondestructively evaluating the state of cartilage. Imaging strategies that allow visualization of cartilage integrity would revolutionize the field by allowing us to visualize early stages of degeneration and thus to evaluate predisposing factors for cartilage disease and changes resulting from interventions (eg, therapies) in culture studies, tissue-engineered systems, animal models, and in vivo in humans. Here we briefly review current state-of-the-art MRI strategies relevant to understanding and following treatment in early cartilage degeneration. We review MRI as applied to the assessment of the whole joint, of cartilage as a whole (as an organ), of cartilage tissue, and of cartilage molecular composition and structure. Each of these levels is amenable to assessment by MRI and offers different information that, in the long run, will serve as an important element of cartilage imaging.
Topics: Animals; Cartilage Diseases; Cartilage, Articular; Collagen; Contrast Media; Gadolinium DTPA; Humans; Knee Joint; Magnetic Resonance Imaging; Osteoarthritis; Time Factors
PubMed: 11041156
DOI: 10.1097/00004424-200010000-00008 -
Joint Bone Spine Oct 2016Osteoarticular diseases, such as arthritis or osteoarthritis, are multifactorial diseases with an underlying genetic etiology that are challenging to study. Genome-Wide... (Review)
Review
Osteoarticular diseases, such as arthritis or osteoarthritis, are multifactorial diseases with an underlying genetic etiology that are challenging to study. Genome-Wide Association studies (GWAS) have identified several genetic loci associated with these diseases. Epigenetics is a complex mechanism of chromatin and gene modulation through DNA methylation, histone deacetylation or microRNA, which might contribute to the inheritability of disease. Some of these mechanisms have been studied for decades in other diseases or as part of the aging process, where epigenetic changes seem to play an important role. With the implementation of better technological tools, such as the Illumina next generation sequencing, altered methylation of DNA has been linked to articular diseases and these mechanisms have been shown to regulate metalloprotease (MMP) expression and cartilage matrix integrity. Some miRNA have also been identified and more extensively characterized, such as delineation of the role played by miR-140 in chondrogenesis, followed by the discovery of numerous miRNA potentially involved in the epigenetic regulation of osteoarthritic disease. Histone deacetylases have long been linked to aging, particularly with respect to the Sirtuin family with Sirt1 as the major player. Because aging is the major risk factor for osteoarthritis, the involvement of Sirtuins in the etiology of osteoarthritis has been suggested and investigated. All of these fine regulations together shed new light on cartilage disease pathophysiology. We present in this short review an update of the role of these pathways in articular diseases.
Topics: Aging; Arthritis; Cartilage Diseases; DNA Methylation; Epigenesis, Genetic; Histone Deacetylases; Histones; Humans; MicroRNAs
PubMed: 26723856
DOI: 10.1016/j.jbspin.2015.10.004 -
Arthritis and Rheumatism Feb 2004
Topics: Bone Diseases; Bone and Bones; Cartilage Diseases; Cartilage, Articular; Humans; Osteoarthritis
PubMed: 14872473
DOI: 10.1002/art.20051 -
Investigative Radiology Oct 2000The role of subchondral bone in the pathogenesis of cartilage damage has likely been underestimated. Subchondral bone is not only an important shock absorber, but it may... (Review)
Review
The role of subchondral bone in the pathogenesis of cartilage damage has likely been underestimated. Subchondral bone is not only an important shock absorber, but it may also be important for cartilage metabolism. Contrary to many drawings and published reports, the subchondral region is highly vascularized and vulnerable. Its terminal vessels have, in part, direct contact with the deepest hyaline cartilage layer. The perfusion of these vessels accounts for more than 50% of the glucose, oxygen, and water requirements of cartilage. Bony structure, local metabolism, hemodynamics, and vascularization of the subchondral region differ within a single joint and from one joint to another. Owing to these differences, repetitive, chronic overloading or perfusion abnormalities may result in no pathological reaction at all in one joint, while in another joint, these same conditions may lead to osteonecrosis, osteochondritis dissecans, or degenerative changes. According to this common etiological root, similar pathological reactions beginning with marrow edema and necrosis and followed by bone and cartilage fractures, joint deformity, and insufficient healing processes are found in osteonecrosis, osteochondritis dissecans, and degenerative disease as well.
Topics: Biomechanical Phenomena; Bone Diseases; Bone and Bones; Cartilage; Cartilage Diseases; Humans; Hyalin
PubMed: 11041152
DOI: 10.1097/00004424-200010000-00004 -
Investigative Radiology Oct 2000Clinical magnetic resonance imaging of articular cartilage is possible by using techniques that offer high contrast between articular cartilage and adjacent structures... (Review)
Review
Clinical magnetic resonance imaging of articular cartilage is possible by using techniques that offer high contrast between articular cartilage and adjacent structures in reasonable examination times. The fat-suppressed, three-dimensional, spoiled gradient-echo sequence has been reported to be accurate and reliable, and the addition of this sequence to a routine examination does not significantly compromise patient throughput. Fast spin-echo imaging also shows promise in the clinical evaluation of articular cartilage, because the newer, stronger-gradient systems allow thinner slice acquisition with two-dimensional sequences. Together, these sequences allow the evaluation of intrachondral lesions and surface defects. Furthermore, quantitative measurements of cartilage volume for follow-up studies are possible with the use of the fat-suppressed, three-dimensional, spoiled gradient-echo sequence.
Topics: Cartilage Diseases; Cartilage, Articular; Humans; Magnetic Resonance Imaging; Sensitivity and Specificity; Time Factors
PubMed: 11041154
DOI: 10.1097/00004424-200010000-00006 -
The Physician and Sportsmedicine Sep 2013Younger adults, aged < 65 years, increasingly present to their physicians with advanced cartilage disease or post-traumatic osteoarthritis. A number of treatments exist... (Review)
Review
Younger adults, aged < 65 years, increasingly present to their physicians with advanced cartilage disease or post-traumatic osteoarthritis. A number of treatments exist for lessening patient pain and improving patient function. However, many patients are becoming aware of the potential of regenerative therapies and are now seeking solutions to the impaired biology underlying their conditions rather than addressing only their symptoms. Patients do not want to merely lessen their symptoms temporarily with a surgical procedure that replaces damaged tissue, but instead seek correction and repair of the underlying biology to regenerate damaged tissue and alleviate their symptoms altogether. Current therapies for patients with cartilage disease or osteoarthritis range from non-surgical intra-articular injections with biologics, such as hyaluronic acid (HA), to total joint arthroplasty for advanced stages of disease. Total joint arthroplasty is a successful procedure for patients aged > 65 years; however, the limited long-term durability of implanted prostheses decreases the preference of using such methods in more active patients aged < 65 years. The potential of cell-based orthobiologic injection therapies (pertaining to therapeutic injectables that aim to restore the biologic environment and/or structural components of diseased or damaged musculoskeletal tissue) is of tremendous interest for younger, more active patients, and is even more appealing in that such therapy can be delivered at point-of-care in the clinic during an office visit. Notably, the exponential rate of progress in biotechnology has allowed for immediate application of myriad novel therapies prior to clear evidence of benefit from randomized clinical trials. Orthobiologic intra-articular injection therapies include HA and platelet-rich plasma (PRP). We report on current, available findings for a third-generation intra-articular orthobiologic injectable therapy for cartilage disease, bone marrow concentrate (BMC). Bone marrow concentrate contains mesenchymal stem cells (MSCs), hematopoetic stem cells, platelets (containing growth factors), and cytokines. The anti-inflammatory and immunomodulatory properties of bone marrow stem cells (BMSCs) can facilitate regeneration of tissue. Additionally, BMSCs enhance the quality of cartilage repair by increasing aggrecan content and tissue firmness. Following bone marrow aspiration (BMA), BMC is easily prepared using centrifugation, and is available for a same-day procedure with minimal manipulation of cells, thus complying with US Food and Drug Association (FDA) restrictions. To date, there are no published randomized controlled trials on the efficacy of use of autologous BMC intra-articular injections performed as a same-day in-office procedure for treating patients with cartilage disease; however, several publications have reported the ease of use of this method, its strong safety profile, and the fundamental science suggesting great therapeutic potential.
Topics: Animals; Bone Marrow Cells; Bone Marrow Transplantation; Cartilage Diseases; Cartilage, Articular; Humans; Injections, Intra-Articular; Transplantation, Autologous
PubMed: 24113698
DOI: 10.3810/psm.2013.09.2022