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Developmental Dynamics : An Official... Apr 2017Here we review studies identifying regulatory networks responsible for synovial, cartilaginous, and fibrous joint development. Synovial joints, characterized by the... (Review)
Review
Here we review studies identifying regulatory networks responsible for synovial, cartilaginous, and fibrous joint development. Synovial joints, characterized by the fluid-filled synovial space between the bones, are found in high-mobility regions and are the most common type of joint. Cartilaginous joints such as the intervertebral disc unite adjacent bones through either a hyaline cartilage or a fibrocartilage intermediate. Fibrous joints, which include the cranial sutures, form a direct union between bones through fibrous connective tissue. We describe how the distinct morphologic and histogenic characteristics of these joint classes are established during embryonic development. Collectively, these studies reveal that despite the heterogeneity of joint strength and mobility, joint development throughout the skeleton utilizes common signaling networks via long-range morphogen gradients and direct cell-cell contact. This suggests that different joint types represent specialized variants of homologous developmental modules. Identifying the unifying aspects of the signaling networks between joint classes allows a more complete understanding of the signaling code for joint formation, which is critical to improving strategies for joint regeneration and repair. Developmental Dynamics 246:262-274, 2017. © 2016 Wiley Periodicals, Inc.
Topics: Animals; Cartilage, Articular; Gene Regulatory Networks; Humans; Joint Capsule; Joints; Morphogenesis; Regeneration; Signal Transduction
PubMed: 27859991
DOI: 10.1002/dvdy.24472 -
Stem Cells Translational Medicine Aug 2019Patients with late-stage Kellgren-Lawrence knee osteoarthritis received a single intra-articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells...
Patients with late-stage Kellgren-Lawrence knee osteoarthritis received a single intra-articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM-MSCs) in a phase I/IIa trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient-reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast-enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores [WORMS]), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM-MSCs were characterized by a panel of anti-inflammatory markers to predict clinical efficacy. There were no serious adverse events, although four patients had minor, transient adverse events. There were significant overall improvements in KOOS pain, symptoms, quality of life, and WOMAC stiffness relative to baseline; the 50 million dose achieved clinically relevant improvements across most PROMs. WORMS and T2 scores did not change relative to baseline. However, cartilage catabolic biomarkers and MRI synovitis were significantly lower at higher doses. Pro-inflammatory monocytes/macrophages and interleukin 12 levels decreased in the synovial fluid after MSC injection. The panel of BM-MSC anti-inflammatory markers was strongly predictive of PROMs over 12 months. Autologous BM-MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM-MSC dosing and BM-MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis. Stem Cells Translational Medicine 2019;8:746&757.
Topics: Biomarkers; Bone Marrow Cells; Cartilage; Cells, Cultured; Female; Humans; Joint Capsule; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Middle Aged; Osteoarthritis, Knee; Quality of Life; Synovitis; Treatment Outcome
PubMed: 30964245
DOI: 10.1002/sctm.18-0183 -
Frontiers in Endocrinology 2023Osteoarthritis (OA) is a disabling disease with significant morbidity worldwide. OA attacks the large synovial joint, including the peripheral joints and... (Review)
Review
Osteoarthritis (OA) is a disabling disease with significant morbidity worldwide. OA attacks the large synovial joint, including the peripheral joints and temporomandibular joint (TMJ). As a representative of peripheral joint OA, knee OA shares similar symptoms with TMJ OA. However, these two joints also display differences based on their distinct development, anatomy, and physiology. Extracellular vesicles (EVs) are phospholipid bilayer nanoparticles, including exosomes, microvesicles, and apoptotic bodies. EVs contain proteins, lipids, DNA, micro-RNA, and mRNA that regulate tissue homeostasis and cell-to-cell communication, which play an essential role in the progression and treatment of OA. They are likely to partake in mechanical response, extracellular matrix degradation, and inflammatory regulation during OA. More evidence has shown that synovial fluid and synovium-derived EVs may serve as OA biomarkers. More importantly, mesenchymal stem cell-derived EV shows a therapeutic effect on OA. However, the different function of EVs in these two joints is largely unknown based on their distinct biological characteristic. Here, we reviewed the effects of EVs in OA progression and compared the difference between the knee joint and TMJ, and summarized their potential therapeutic role in the treatment of OA.
Topics: Humans; Osteoarthritis; Temporomandibular Joint; Extracellular Vesicles; Synovial Membrane; Synovial Fluid
PubMed: 36950682
DOI: 10.3389/fendo.2023.1158744 -
Frontiers in Immunology 2020
Topics: Animals; Antirheumatic Agents; Arthritis, Rheumatoid; Humans; Inflammation Mediators; Phenotype; RNA, Long Noncoding; Signal Transduction; Synovial Membrane; Synoviocytes
PubMed: 32508834
DOI: 10.3389/fimmu.2020.00955 -
Arthritis & Rheumatology (Hoboken, N.J.) Nov 2018
Topics: Americas; Arthritis; Chikungunya Fever; Cross-Sectional Studies; Humans; Synovial Fluid
PubMed: 30003684
DOI: 10.1002/art.40664 -
Cellular and Molecular Life Sciences :... Oct 2019Articular cartilage is formed at the end of epiphyses in the synovial joint cavity and permanently contributes to the smooth movement of synovial joints. Most skeletal... (Review)
Review
Articular cartilage is formed at the end of epiphyses in the synovial joint cavity and permanently contributes to the smooth movement of synovial joints. Most skeletal elements develop from transient cartilage by a biological process known as endochondral ossification. Accumulating evidence indicates that articular and growth plate cartilage are derived from different cell sources and that different molecules and signaling pathways regulate these two kinds of cartilage. As the first sign of joint development, the interzone emerges at the presumptive joint site within a pre-cartilage tissue. After that, joint cavitation occurs in the center of the interzone, and the cells in the interzone and its surroundings gradually form articular cartilage and the synovial joint. During joint development, the interzone cells continuously migrate out to the epiphyseal cartilage and the surrounding cells influx into the joint region. These complicated phenomena are regulated by various molecules and signaling pathways, including GDF5, Wnt, IHH, PTHrP, BMP, TGF-β, and FGF. Here, we summarize current literature and discuss the molecular mechanisms underlying joint formation and articular development.
Topics: Animals; Bone Morphogenetic Proteins; Cartilage, Articular; Cell Differentiation; Cell Lineage; Cell Movement; Chondrocytes; Chondrogenesis; Fibroblast Growth Factors; Gene Expression Regulation; Growth Differentiation Factor 5; Hedgehog Proteins; Humans; Joint Capsule; Osteogenesis; Parathyroid Hormone-Related Protein; Transforming Growth Factor beta; Wnt Signaling Pathway
PubMed: 31201464
DOI: 10.1007/s00018-019-03191-5 -
Biomedical Journal Apr 2021Rheumatoid arthritis (RA) is an autoimmune disease affecting ∼1% of the general population. This disease is characterized by persistent articular inflammation and... (Review)
Review
Rheumatoid arthritis (RA) is an autoimmune disease affecting ∼1% of the general population. This disease is characterized by persistent articular inflammation and joint damage driven by the proliferating synovial tissue fibroblasts as well as neutrophil, monocyte and lymphocyte trafficking into the synovium. The factors leading to RA pathogenesis remain poorly elucidated although genetic and environmental factors have been proposed to be the main contributors to RA. The majority of the early studies focused on the role of lymphocytes and adaptive immune responses in RA. However, in the past two decades, emerging studies showed that the innate immune system plays a critical role in the onset and progression of RA pathogenesis. Various innate immune cells including monocytes, macrophages and dendritic cells are involved in inflammatory responses seen in RA patients as well as in driving the activation of the adaptive immune system, which plays a major role in the later stages of the disease. Here we focus the discussion on the role of different innate immune cells and components in initiation and progression of RA. New therapeutic approaches targeting different inflammatory pathways and innate immune cells will be highlighted here. Recent emergence and the significant roles of innate lymphoid cells and inflammasomes will be also discussed.
Topics: Arthritis, Rheumatoid; Humans; Immunity, Innate; Lymphocytes; Macrophages; Synovial Membrane
PubMed: 32798211
DOI: 10.1016/j.bj.2020.06.010 -
BMC Musculoskeletal Disorders Jul 2022Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism... (Review)
Review
Arthrofibrosis, or rigid contracture of major articular joints, is a significant morbidity of many neurodegenerative disorders. The pathogenesis depends on the mechanism and severity of the precipitating neuromuscular disorder. Most neuromuscular disorders, whether spastic or hypotonic, culminate in decreased joint range of motion. Limited range of motion precipitates a cascade of pathophysiological changes in the muscle-tendon unit, the joint capsule, and the articular cartilage. Resulting joint contractures limit functional mobility, posing both physical and psychosocial burdens to patients, economic burdens on the healthcare system, and lost productivity to society. This article reviews the pathophysiology of arthrofibrosis in the setting of neuromuscular disorders. We describe current non-surgical and surgical interventions for treating arthrofibrosis of commonly affected joints. In addition, we preview several promising modalities under development to ameliorate arthrofibrosis non-surgically and discuss limitations in the field of arthrofibrosis secondary to neuromuscular disorders.
Topics: Contracture; Fibrosis; Humans; Joint Capsule; Joint Diseases; Joints; Knee Joint; Range of Motion, Articular
PubMed: 35906570
DOI: 10.1186/s12891-022-05677-z -
Stem Cell Research & Therapy Sep 2023Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease of unknown etiology. The most common form of this disease is chronic inflammatory arthritis, which... (Review)
Review
Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease of unknown etiology. The most common form of this disease is chronic inflammatory arthritis, which begins with inflammation of the synovial membrane of the affected joints and eventually leads to disability of the affected limb. Despite significant advances in RA pharmaceutical therapies and the availability of a variety of medicines on the market, none of the available medicinal therapies has been able to completely cure the disease. In addition, a significant percentage (30-40%) of patients do not respond appropriately to any of the available medicines. Recently, mesenchymal stromal cells (MSCs) have shown promising results in controlling inflammatory and autoimmune diseases, including RA. Experimental studies and clinical trials have demonstrated the high power of MSCs in modulating the immune system. In this article, we first examine the mechanism of RA disease, the role of cytokines and existing medicinal therapies. We then discuss the immunomodulatory function of MSCs from different perspectives. Our understanding of how MSCs work in suppressing the immune system will lead to better utilization of these cells as a promising tool in the treatment of autoimmune diseases.
Topics: Humans; Arthritis, Rheumatoid; Synovial Membrane; Mesenchymal Stem Cells; Cytokines; Inflammation
PubMed: 37741991
DOI: 10.1186/s13287-023-03473-7 -
Anatomical Record (Hoboken, N.J. : 2007) Sep 2022We continued direct morphological studies of the canid coxofemoral joint, considering early-life spatial relationships around the locus of the proximocaudal joint...
We continued direct morphological studies of the canid coxofemoral joint, considering early-life spatial relationships around the locus of the proximocaudal joint capsule insertion. Our primary goal was to elucidate the postnatal developmental gross anatomy of the proximocaudal femur, among juveniles across Canidae. From an original database of 267 independent (museum) specimens from 11 canid taxa and 1 hybrid taxon, we identified 29 ancient or modern candidate juvenile specimens (nine taxa and one hybrid taxon). Based on optimal ability to recognize landmarks, the best photographic data were categorized into five groups of four each (n = 20). The data groups approximated early juvenile, early-mid juvenile, mid-juvenile, mid-late juvenile; and young adult stages. In this descriptive photographic essay, we demonstrate the developmental spatial proximity among (a) the dorsal meeting of the respective lateral and medial extensions from the growth centers of the femoral head and greater trochanter; (b) the caudodorsal aspect of the coxofemoral joint capsule attachment; (c) a segment of the proximocaudal femoral shaft physis; and (d) an eventual associated mineralized prominence. The latter occurs frequently but not universally, suggesting natural population variability across taxa. Across taxa and juvenile age categories, the morphology thus supports developmental conservation among ancient and modern Canidae. The biomechanical and biological cause-effect implications are not yet clear. For zoological purposes, we apply the term postdevelopmental mineralized prominence to the residual caudolateral surface feature. We extend the original anatomical work of Morgan in zoological and phylogenic arenas, using direct observation of cleared skeletal specimens.
Topics: Animals; Canidae; Femur; Femur Head; Hip Joint; Joint Capsule
PubMed: 34854568
DOI: 10.1002/ar.24848