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Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis.RMD Open 2019DNA of gut microbiota can be found in synovium of osteoarthritis and rheumatoid arthritis. This finding could result from the translocation of still alive bacteria from... (Review)
Review
DNA of gut microbiota can be found in synovium of osteoarthritis and rheumatoid arthritis. This finding could result from the translocation of still alive bacteria from gut to joints through blood, since the diversified dormant microbiota of healthy human blood can be transiently resuscitated in vitro. The recent finding of gut microbiome in human cartilage, which differed between osteoarthritis and controls, suggests that a similar trafficking of dead or alive bacteria from gut microbiota physiologically occurs between gut and epiphysial bone marrow. Subchondral microbiota could enhance cartilage healing and transform components of deep cartilage matrix in metabolites with immunosuppressive properties. The differences of microbiome observed between hip and knee cartilage, either in osteoarthritis or controls, might be the counterpart of subtle differences in chondrocyte metabolism, themselves in line with differences in DNA methylation according to joints. Although bacteria theoretically cannot reach chondrocytes from the surface of intact cartilage, some bacteria enter the vascular channels of the epiphysial growth cartilage in young animals, whereas others can infect chondrocytes in vitro. In osteoarthritis, the early osteochondral plate angiogenesis may further enhance the ability of microbiota to locate close to the deeper layers of cartilage, and this might lead to focal dysbiosis, low-grade inflammation, cartilage degradation, epigenetic changes in chondrocytes and worsening of osteoarthritis. More studies on cartilage across different ethnic groups, weights, and according to age, are needed, to confirm the silent presence of gut microbiota close to human cartilage and better understand its physiologic and pathogenic significance.
Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Cartilage, Articular; Chondrocytes; DNA Methylation; Gastrointestinal Microbiome; Hip Joint; Humans; Knee Joint; Metabolomics; Osteoarthritis
PubMed: 31673418
DOI: 10.1136/rmdopen-2019-001037 -
International Journal of Molecular... Oct 2023This review presents the changes that the imaging of articular cartilage has undergone throughout the last decades. It highlights that the expectation is no longer to... (Review)
Review
This review presents the changes that the imaging of articular cartilage has undergone throughout the last decades. It highlights that the expectation is no longer to image the structure and associated functions of articular cartilage but, instead, to devise methods for generating non-invasive, function-depicting images with quantitative information that is useful for detecting the early, pre-clinical stage of diseases such as primary or post-traumatic osteoarthritis (OA/PTOA). In this context, this review summarizes (a) the structure and function of articular cartilage as a molecular imaging target, (b) quantitative MRI for non-invasive assessment of articular cartilage composition, microstructure, and function with the current state of medical diagnostic imaging, (c), non-destructive imaging methods, (c) non-destructive quantitative articular cartilage live-imaging methods, (d) artificial intelligence (AI) classification of degeneration and prediction of OA progression, and (e) our contribution to this field, which is an AI-supported, non-destructive quantitative optical biopsy for early disease detection that operates on a digital tissue architectural fingerprint. Collectively, this review shows that articular cartilage imaging has undergone profound changes in the purpose and expectations for which cartilage imaging is used; the image is becoming an AI-usable biomarker with non-invasive quantitative functional information. This may aid in the development of translational diagnostic applications and preventive or early therapeutic interventions that are yet beyond our reach.
Topics: Humans; Cartilage, Articular; Artificial Intelligence; Osteoarthritis; Magnetic Resonance Imaging; Research
PubMed: 37834422
DOI: 10.3390/ijms241914974 -
Radiology Jul 2016Bone or cartilage, or both, are frequently injured related to either a single episode of trauma or repetitive overuse. The resulting structural damage is varied,... (Review)
Review
Bone or cartilage, or both, are frequently injured related to either a single episode of trauma or repetitive overuse. The resulting structural damage is varied, governed by the complex macroscopic and microscopic composition of these tissues. Furthermore, the biomechanical properties of both cartilage and bone are not uniform, influenced by the precise age and activity level of the person and the specific anatomic location within the skeleton. Of the various histologic components that are found in cartilage and bone, the collagen fibers and bundles are most influential in transmitting the forces that are applied to them, explaining in large part the location and direction of the resulting internal stresses that develop within these tissues. Therefore, thorough knowledge of the anatomy, physiology, and biomechanics of normal bone and cartilage serves as a prerequisite to a full understanding of both the manner in which these tissues adapt to physiologic stresses and the patterns of tissue failure that develop under abnormal conditions. Such knowledge forms the basis for more accurate assessment of the diverse imaging features that are encountered following acute traumatic and stress-related injuries to the skeleton. (©) RSNA, 2016.
Topics: Acute Disease; Biomechanical Phenomena; Bone and Bones; Cartilage, Articular; Fractures, Bone; Fractures, Stress; Humans; Magnetic Resonance Imaging; Radiography; Stress, Physiological
PubMed: 27322971
DOI: 10.1148/radiol.16142305 -
Archives of Orthopaedic and Trauma... Jun 2023Cartilage tissue has a very limited ability to regenerate. Symptomatic cartilage lesions are currently treated by various cartilage repair techniques. Multiple treatment... (Review)
Review
Cartilage tissue has a very limited ability to regenerate. Symptomatic cartilage lesions are currently treated by various cartilage repair techniques. Multiple treatment techniques have been proposed in the last 30 years. Nevertheless, no single technique is accepted as a gold standard. Minced cartilage implantation is a newer technique that has garnered increasing attention. This procedure is attractive because it is autologous, can be performed in a single surgery, and is therefore given it is cost-effective. This narrative review provides an overview of the biological potential of current cartilage regenerative repair techniques with a focus on the translational evidence of minced cartilage implantation.
Topics: Humans; Chondrocytes; Cartilage, Articular; Regeneration; Transplantation, Autologous; Biological Products
PubMed: 36385655
DOI: 10.1007/s00402-022-04692-y -
Scientific Reports Feb 2020Osteoarthritis (OA) is the most common arthritis and its hallmark is degradation of articular cartilage by proteolytic enzymes leading to loss of joint function. It is...
Osteoarthritis (OA) is the most common arthritis and its hallmark is degradation of articular cartilage by proteolytic enzymes leading to loss of joint function. It is challenging to monitor the status of cartilage in vivo and this study explores the use of autofluorescence lifetime (AFL) measurements to provide a label-free optical readout of cartilage degradation that could enable earlier detection and evaluation of potential therapies. We previously reported that treatment of ex vivo porcine cartilage with proteolytic enzymes resulted in decreased AFL. Here we report changes in AFL of ex vivo mouse knee joints, porcine metacarpophalangeal joints, normal human metatarsophalangeal articular tissue and human OA tibial plateau tissues measured with or without treatment using a compact single-point time resolved spectrofluorometer. Our data show that proteolytically damaged areas in porcine metacarpophalangeal joints present a reduced AFL and that inducing aggrecanases in mouse and human joints also significantly reduces AFL. Further, human cartilage from OA patients presents a significantly lower AFL compared to normal human cartilage. Our data suggest that AFL can detect areas of cartilage erosion and may potentially be utilised as a minimally-invasive diagnostic readout for early stage OA in combination with arthroscopy devices.
Topics: Animals; Cartilage, Articular; Fluorescence; Fluorometry; Humans; Male; Mice; Mice, Inbred C57BL; Optical Imaging; Osteoarthritis; Proteolysis; Swine; Trypsin
PubMed: 32034262
DOI: 10.1038/s41598-020-59219-5 -
International Journal of Molecular... Dec 2021Several collagen subtypes have been identified in hyaline articular cartilage. The main and most abundant collagens are type II, IX and XI collagens. The minor and less... (Review)
Review
Several collagen subtypes have been identified in hyaline articular cartilage. The main and most abundant collagens are type II, IX and XI collagens. The minor and less abundant collagens are type III, IV, V, VI, X, XII, XIV, XVI, XXII, and XXVII collagens. All these collagens have been found to play a key role in healthy cartilage, regardless of whether they are more or less abundant. Additionally, an exhaustive evaluation of collagen fibrils in a repaired cartilage tissue after a chondral lesion is necessary to determine the quality of the repaired tissue and even whether or not this repaired tissue is considered hyaline cartilage. Therefore, this review aims to describe in depth all the collagen types found in the normal articular cartilage structure, and based on this, establish the parameters that allow one to consider a repaired cartilage tissue as a hyaline cartilage.
Topics: Animals; Cartilage Diseases; Cartilage, Articular; Collagen; Humans; Hyaline Cartilage
PubMed: 34948124
DOI: 10.3390/ijms222413329 -
Osteoarthritis and Cartilage Jun 2024To investigate the feasibility of using neutron tomography to gain new knowledge of human articular cartilage degeneration in osteoarthritis (OA). Different sample...
OBJECTIVE
To investigate the feasibility of using neutron tomography to gain new knowledge of human articular cartilage degeneration in osteoarthritis (OA). Different sample preparation techniques were evaluated to identify maximum intra-tissue contrast.
DESIGN
Human articular cartilage samples from 14 deceased donors (18-75 years, 9 males, 5 females) and 4 patients undergoing total knee replacement due to known OA (all female, 61-75 years) were prepared using different techniques: control in saline, treated with heavy water saline, fixed and treated in heavy water saline, and fixed and dehydrated with ethanol. Neutron tomographic imaging (isotropic voxel sizes from 7.5 to 13.5 µm) was performed at two large scale facilities. The 3D images were evaluated for gradients in hydrogen attenuation as well as compared to images from absorption X-ray tomography, magnetic resonance imaging, and histology.
RESULTS
Cartilage was distinguishable from background and other tissues in neutron tomographs. Intra-tissue contrast was highest in heavy water-treated samples, which showed a clear gradient from the cartilage surface to the bone interface. Increased neutron flux or exposure time improved image quality but did not affect the ability to detect gradients. Samples from older donors showed high variation in gradient profile, especially from donors with known OA.
CONCLUSIONS
Neutron tomography is a viable technique for specialized studies of cartilage, particularly for quantifying properties relating to the hydrogen density of the tissue matrix or water movement in the tissue.
Topics: Humans; Cartilage, Articular; Middle Aged; Female; Adult; Aged; Male; Adolescent; Young Adult; Feasibility Studies; Osteoarthritis, Knee; Tomography; Magnetic Resonance Imaging; Neutrons; Imaging, Three-Dimensional
PubMed: 38447631
DOI: 10.1016/j.joca.2024.02.889 -
Journal of the Mechanical Behavior of... Feb 2023Numerical simulations are a valuable tool to understand which processes during mechanical stimulations of hydrogels for cartilage replacement influence the behavior of...
Numerical simulations are a valuable tool to understand which processes during mechanical stimulations of hydrogels for cartilage replacement influence the behavior of chondrocytes and contribute to the success or failure of these materials as implants. Such simulations critically rely on the correct prediction of the material response through appropriate material models and corresponding parameters. In this study, we identify hyper-viscoelastic material parameters for numerical simulations in COMSOL Multiphysics® v. 5.6 for human articular cartilage and two replacement materials, the commercially available ChondroFiller and oxidized alginate gelatin (ADA-GEL) hydrogels. We incorporate the realistic experimental boundary conditions into an inverse parameter identification scheme based on data from multiple loading modes simultaneously, including cyclic compression-tension and stress relaxation experiments. We provide individual parameter sets for the unconditioned and conditioned responses and discuss how viscoelastic effects are related to the materials' microstructure. ADA-GEL and ChondroFiller exhibit faster stress relaxation than cartilage with lower relaxation time constants, while cartilage has the largest viscoelastic stress contribution. The elastic response predominates in ADA-GEL and ChondroFiller, while the viscoelastic response predominates in cartilage. These results will help to simulate mechanical stimulations, support the development of suitable materials with distinct mechanical properties in the future and provide parameters and insight into the time-dependent material behavior of human articular cartilage.
Topics: Humans; Cartilage, Articular; Elasticity; Viscosity; Chondrocytes; Hydrogels; Stress, Mechanical
PubMed: 36566662
DOI: 10.1016/j.jmbbm.2022.105618 -
Current Rheumatology Reports Nov 2014Efforts to reduce the ever-increasing rates of osteoarthritis (OA) in the developed world require the ability to non-invasively detect the degradation of joint tissues... (Review)
Review
Efforts to reduce the ever-increasing rates of osteoarthritis (OA) in the developed world require the ability to non-invasively detect the degradation of joint tissues before advanced damage has occurred. This is particularly relevant for damage to articular cartilage because this soft tissue lacks the capacity to repair itself following major damage and is essential to proper joint function. While conventional magnetic resonance imaging (MRI) provides sufficient contrast to visualize articular cartilage morphology, more advanced imaging strategies are necessary for understanding the underlying biochemical composition of cartilage that begins to break down in the earliest stages of OA. This review discusses the biochemical basis and the advantages and disadvantages associated with each of these techniques. Recent implementations for these techniques are touched upon, and future considerations for improving the research and clinical power of these imaging technologies are also discussed.
Topics: Arthrography; Cartilage, Articular; Contrast Media; Humans; Magnetic Resonance Imaging; Osteoarthritis; Tomography, X-Ray Computed
PubMed: 25218737
DOI: 10.1007/s11926-014-0462-3 -
Journal of Biomechanics Oct 2019Articular cartilage is an enduring tissue. For most individuals, articular cartilage facilitates a lifetime of pain-free ambulation, supporting millions of loading...
Articular cartilage is an enduring tissue. For most individuals, articular cartilage facilitates a lifetime of pain-free ambulation, supporting millions of loading cycles from activities of daily living. Although early studies into osteoarthritis focused on the role of mechanical fatigue in articular cartilage degeneration, much is still unknown regarding its strength and endurance characteristics. The compressive strength of juvenile, bovine articular cartilage explants was determined to be loading rate-dependent, reaching a maximum strength of 29.5 ± 4.8 MPa at a strain rate of 0.10 %/sec. The fatigue and endurance properties of articular cartilage were characterized utilizing a material testing system, as well as a custom, validated instrument termed the two degrees-of-freedom endurance meter (endurometer). These instruments characterized fatigue in articular cartilage explants at loading levels ranging from 10 to 80 % strength (%S), up to 100,000 cycles. Cartilage explants displayed characteristics of fatigue - fatigue life increased as the loading magnitude decreased. All explants failed within 14,000 cycles at loading levels between 50 and 80 %S. At 10 and 20 %S, all explants endured 100,000 loading cycles. There was no significant difference in equilibrium compressive modulus between run-out explants and unloaded controls, although the pooled modulus increased in response to testing. Histological staining and biochemical assays revealed no material changes in collagen, sulfated glycosaminoglycan, or hydration content between unloaded controls and explants cyclically loaded to run-out. These results suggest articular cartilage may have a putative endurance limit of 20 %S (5.86 MPa), with implications for articular cartilage biomechanics and mechanobiology.
Topics: Animals; Cartilage, Articular; Cattle; Chondrocytes; Collagen; Compressive Strength; Glycosaminoglycans; Pressure; Stress, Mechanical; Weight-Bearing
PubMed: 31447176
DOI: 10.1016/j.jbiomech.2019.07.048