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Frontiers in Immunology 2021Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response.... (Review)
Review
Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: "a macrophage niche". These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.
Topics: Cell Movement; Humans; Knee Joint; Macrophages; Monocytes; Osteoarthritis; Synovial Membrane
PubMed: 34804052
DOI: 10.3389/fimmu.2021.763702 -
Birth Defects Research. Part C, Embryo... Sep 2013Articular cartilage is classified as permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile,... (Review)
Review
Articular cartilage is classified as permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in the epiphyseal growth plate. In the process of synovial joint development, articular cartilage originates from the interzone, developing at the edge of the cartilaginous anlagen, and establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators, such as Wnts, GDF5, Erg, and PTHLH, coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracellular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier's groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Furthermore, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site.
Topics: Animals; Cartilage, Articular; Cell Differentiation; Chondrocytes; Chondrogenesis; Humans; Joints; Models, Animal; Phenotype; Regeneration; Stem Cell Transplantation; Stem Cells
PubMed: 24078496
DOI: 10.1002/bdrc.21042 -
Nature Communications Feb 2023Massive intra-articular infiltration of proinflammatory macrophages is a prominent feature of rheumatoid arthritis (RA) lesions, which are thought to underlie articular...
Massive intra-articular infiltration of proinflammatory macrophages is a prominent feature of rheumatoid arthritis (RA) lesions, which are thought to underlie articular immune dysfunction, severe synovitis and ultimately joint erosion. Here we report an efferocytosis-informed nanoimitator (EINI) for in situ targeted reprogramming of synovial inflammatory macrophages (SIMs) that thwarts their autoimmune attack and reestablishes articular immune homeostasis, which mitigates RA. The EINI consists of a drug-based core with an oxidative stress-responsive phosphatidylserine (PtdSer) corona and a shell composed of a P-selectin-blocking motif, low molecular weight heparin (LMWH). When systemically administered, the LMWH on the EINI first binds to P-selectin overexpressed on the endothelium in subsynovial capillaries, which functions as an antagonist, disrupting neutrophil synovial trafficking. Due to the strong dysregulation of the synovial microvasculature, the EINI is subsequently enriched in the joint synovium where the shell is disassembled upon the reactive oxygen species stimulation, and PtdSer corona is then exposed. In an efferocytosis-like manner, the PtdSer-coroneted core is in turn phagocytosed by SIMs, which synergistically terminate SIM-initiated pathological cascades and serially reestablish intra-articular immune homeostasis, conferring a chondroprotective effect. These findings demonstrate that SIMs can be precisely remodeled via the efferocytosis-mimetic strategy, which holds potential for RA treatment.
Topics: Mice; Animals; P-Selectin; Heparin, Low-Molecular-Weight; Arthritis, Rheumatoid; Joints; Synovial Membrane
PubMed: 36781864
DOI: 10.1038/s41467-023-36468-2 -
Osteoarthritis and Cartilage 2008This review addresses the use of ultrasound (US) as an imaging technique for the evaluation and monitoring of the osteoarthritic joint. US complements both the clinical... (Review)
Review
This review addresses the use of ultrasound (US) as an imaging technique for the evaluation and monitoring of the osteoarthritic joint. US complements both the clinical examination and radiological imaging by allowing the rheumatologist to recognize not only the bony profile but also to visualize the soft tissues. Systematic US scanning following established guidelines can demonstrate even minimal abnormalities of articular cartilage, bony cortex and synovial tissue. US is also extremely sensitive in the detection of soft tissue changes in the involved joints including the proliferation of the synovium and changes in the amount of fluid present within the joint. Monitoring the amount of fluid in the hip and knee joint with osteoarthritis may be a potentially useful finding in the selection of patients for clinical investigation and for assessing their response to therapeutic interventions.
Topics: Cartilage, Articular; Disease Progression; Humans; Image Processing, Computer-Assisted; Knee Joint; Osteoarthritis, Knee; Synovial Membrane; Ultrasonography
PubMed: 18760636
DOI: 10.1016/j.joca.2008.06.005 -
Current Topics in Developmental Biology 2019The joints are a diverse group of skeletal structures, and their genesis, morphogenesis, and acquisition of specialized tissues have intrigued biologists for decades.... (Review)
Review
The joints are a diverse group of skeletal structures, and their genesis, morphogenesis, and acquisition of specialized tissues have intrigued biologists for decades. Here we review past and recent studies on important aspects of joint development, including the roles of the interzone and morphogenesis of articular cartilage. Studies have documented the requirement of interzone cells in limb joint initiation and formation of most, if not all, joint tissues. We highlight these studies and also report more detailed interzone dissection experiments in chick embryos. Articular cartilage has always received special attention owing to its complex architecture and phenotype and its importance in long-term joint function. We pay particular attention to mechanisms by which neonatal articular cartilage grows and thickens over time and eventually acquires its multi-zone structure and becomes mechanically fit in adults. These and other studies are placed in the context of evolutionary biology, specifically regarding the dramatic changes in limb joint organization during transition from aquatic to land life. We describe previous studies, and include new data, on the knee joints of aquatic axolotls that unlike those in higher vertebrates, are not cavitated, are filled with rigid fibrous tissues and resemble amphiarthroses. We show that when axolotls metamorph to life on land, their intra-knee fibrous tissue becomes sparse and seemingly more flexible and the articular cartilage becomes distinct and acquires a tidemark. In sum, there have been considerable advances toward a better understanding of limb joint development, biological responsiveness, and evolutionary influences, though much remains unclear. Future progress in these fields should also lead to creation of new developmental biology-based tools to repair and regenerate joint tissues in acute and chronic conditions.
Topics: Animals; Biological Evolution; Bone and Bones; Cartilage, Articular; Cell Lineage; Humans; Joints; Morphogenesis
PubMed: 30902250
DOI: 10.1016/bs.ctdb.2018.11.002 -
Scientific Reports Nov 2022Stokes's equation in the fluid domain and Brinkman's equation in the porous media are combined in the current study which is designated by the Stokes-Brinkman coupling....
Stokes's equation in the fluid domain and Brinkman's equation in the porous media are combined in the current study which is designated by the Stokes-Brinkman coupling. The current paper gives a theoretical analysis of the Stokes-Brinkman coupling. It has been shown that such a model is a good match for the knee joint. A flow model has been investigated in order to get a better understanding of the convective diffusion of the viscous flow along the articular surfaces between the joints. The Beavers and Joseph slip conditions which are a specific boundary condition for the synovial fluid are used to solve the governing system of partial differential equations for the synovial fluid and the results are provided here. We develop formulas for the interfacial velocity for both flow through special slip condition and analyse the link between the slip parameters [Formula: see text] and [Formula: see text]. Thus, the damping force due to the porous medium naturally when we non-dimensionalize, some parameter which are controlling the structure like, [Formula: see text] and [Formula: see text]. Through the development of an analytical solution and numerical simulation (using the finite volume approach) it is hoped that the mechanisms of nutritional transport into the synovial joint will be better understood. According to the data the average concentration has a negative connection with both the axial distance and the duration spent in the experiment. Many graphs have been utilized to gain understanding into the problem's various characteristics including velocity and concentration, among others. Hyaluronate (HA) is considered to be present in porous cartilage surfaces and the viscosity of synovial fluid fluctuates in response to the amount of HA present.
Topics: Humans; Porosity; Viscosity; Computer Simulation; Knee Joint; Synovial Fluid
PubMed: 36348000
DOI: 10.1038/s41598-022-23402-7 -
Annals of the Rheumatic Diseases Dec 1984The joints of 124 young adult patients with bilharziasis were examined. Heels, sacroiliac joints, cervical spine, knee joint, dorsal spine, and tarsal joints were...
The joints of 124 young adult patients with bilharziasis were examined. Heels, sacroiliac joints, cervical spine, knee joint, dorsal spine, and tarsal joints were affected. Biopsy of the knee synovia showed synovitis, vasculitis, and the presence of bilharzial ova in three cases. Radiologically the heels and sacroiliac joints showed inflammatory changes. Schistosomiasis may cause an arthropathy.
Topics: Adolescent; Adult; Arthritis, Infectious; Child; Heel; Humans; Knee Joint; Male; Parasite Egg Count; Sacroiliac Joint; Schistosomiasis; Synovial Membrane
PubMed: 6524982
DOI: 10.1136/ard.43.6.806 -
Osteoarthritis and Cartilage Jan 2016This narrative review covers original publications related to imaging in osteoarthritis (OA) published in English between 1 April 2014 and 30 April 2015. Novel lessons... (Review)
Review
PURPOSE
This narrative review covers original publications related to imaging in osteoarthritis (OA) published in English between 1 April 2014 and 30 April 2015. Novel lessons relating to imaging are described.
METHODS
An extensive PubMed database search was performed based on, but not limited to the terms "OA" in combination with "Magnetic resonance imaging (MRI)", "Imaging", "Radiography", "Ultrasound", "Computed tomography (CT)" and "Nuclear medicine" to extract relevant studies. In vitro data and animal studies were excluded. This review focuses on the new developments and observations based on the aforementioned imaging modalities, as well as a 'whole-organ' approach by presenting findings from different tissues (bone, meniscus, synovium, muscle and fat) and joints (hip, lumbar spine and hand).
RESULTS AND CONCLUSIONS
Over the past year, studies using imagine have made a major contribution to the understanding of the pathogenesis of OA. Significant work has continued at the knee, with MRI now being increasingly used to assess structural endpoints in clinical trials. This offers the exciting opportunity to explore potential disease modifying OA therapies. There has been a clear interest in the role of bone in the pathogenesis of OA. There is now a growing body of literature examining the pathogenesis of OA at the hip, lumbar spine and hand. The future of imaging in OA offers the exciting potential to better understand the disease process across all joints and develop more effective preventive and therapeutic interventions.
Topics: Arthrography; Cartilage, Articular; Humans; Joints; Knee Joint; Magnetic Resonance Imaging; Osteoarthritis; Radionuclide Imaging; Synovial Membrane; Tomography, X-Ray Computed; Ultrasonography
PubMed: 26707992
DOI: 10.1016/j.joca.2015.07.027 -
Archivum Immunologiae Et Therapiae... Apr 2011Synovial mesenchymal cells, matrix metalloproteinases (MMPs), and osteoclasts are the three major players directly responsible for the pathogenesis of rheumatoid joint... (Review)
Review
Synovial mesenchymal cells, matrix metalloproteinases (MMPs), and osteoclasts are the three major players directly responsible for the pathogenesis of rheumatoid joint destruction. First, synovial mesenchymal cells, internally driven by a transcription factor c-Fos/AP-1, not only directly invade cartilage and bone as a granulation tissue called "pannus" but also release inflammatory cytokine interleukin (IL)-1β. IL-1β induces MMPs and activates osteoclasts. Synovial cells can also present antigen to T cells to drive antigen-specific immune responses. Second, cartilaginous joint matrix can only be degraded after the first attack of collagen fibrils by MMPs, and importantly, most of the MMPs are under the control of c-Fos/AP-1 and IL-1β as well. Third, differentiation of osteoclast is driven internally by NFATc1, where NFATc1 is under the control of TRAF6, c-Fos/AP-1 and osteoclastogenic signaling complex. IL-1β has been shown to induce osteoclastogenesis directly and also indirectly via signaling through RANKL. Therefore, IL-1β and c-Fos/AP-1 influence each other's gene expression and activity, resulting in an orchestrated cross-talk that is crucial to arthritic joint destruction, and thus, blockade of IL-1β and/or c-Fos/AP-1 can be most promising as a therapeutic target, and in fact, a selective inhibition of c-Fos/AP-1 does resolve arthritic joint destruction.
Topics: Animals; Arthritis, Rheumatoid; Humans; Inflammation Mediators; Joints; Matrix Metalloproteinases; Mesoderm; Osteoclasts; Signal Transduction; Synovial Membrane
PubMed: 21327737
DOI: 10.1007/s00005-011-0116-3 -
International Journal of Molecular... Jul 2023Osteoarthritis (OA) is a multifactorial disease in which genetics, aging, obesity, and trauma are well-known risk factors. It is the most prevalent joint disease and the... (Review)
Review
Osteoarthritis (OA) is a multifactorial disease in which genetics, aging, obesity, and trauma are well-known risk factors. It is the most prevalent joint disease and the largest disability problem worldwide. Recent findings have described the role of damage-associated molecular patterns (DAMPs) in the course of the disease. In particular, alarmins such as HMGB1, IL-33, and S100B, appear implicated in enhancing articular inflammation and favouring a catabolic switch in OA chondrocytes. The aims of this review are to clarify the molecular signalling of these three molecules in OA pathogenesis, to identify their possible use as staging biomarkers, and, most importantly, to find out whether they could be possible therapeutic targets. Osteoarthritic cartilage expresses increased levels of all three alarmins. HMGB1, in particular, is the most studied alarmin with increased levels in cartilage, synovium, and synovial fluid of OA patients. High levels of HMGB1 in synovial fluid of OA joints are positively correlated with radiological and clinical severity. Counteracting HMGB1 strategies have revealed improving results in articular cells from OA patients and in OA animal models. Therefore, drugs against this alarmin, such as anti-HMGB1 antibodies, could be new treatment possibilities that can modify the disease course since available medications only alleviate symptoms.
Topics: Animals; Alarmins; Cartilage, Articular; Chondrocytes; HMGB1 Protein; Interleukin-33; Joints; Osteoarthritis; Synovial Membrane
PubMed: 37569519
DOI: 10.3390/ijms241512143