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International Journal of Molecular... Sep 2020Osteoarthritis (OA) is the most common degenerative joint disease, predicted to increase in incidence year by year due to an ageing population. Due to the biological... (Review)
Review
Osteoarthritis (OA) is the most common degenerative joint disease, predicted to increase in incidence year by year due to an ageing population. Due to the biological complexity of the disease, OA remains highly heterogeneous. Although much work has been undertaken in the past few years, underlying molecular mechanisms leading to joint tissue structural deterioration are not fully understood, with only few validated markers for disease diagnosis and progression being available. Discovery and quantitation of various OA-specific biomarkers is still largely focused on the bodily fluids which does not appear to be reliable and sensitive enough. However, with the advancement of spatial proteomic techniques, several novel peptides and proteins, as well as N-glycans, can be identified and localised in a reliable and sensitive manner. To summarise the important findings from OA biomarker studies, papers published between 2000 and 2020 were searched via Google Scholar and PubMed. Medical subject heading (MeSH) terms 'osteoarthritis', 'biomarker', 'synovial fluid', 'serum', 'urine', 'matrix-assisted laser desorption/ionisation', 'mass spectrometry imaging', 'proteomic', 'glycomic', 'cartilage', 'synovium' AND 'subchondral bone' were selectively used. The literature search was restricted to full-text original research articles and written only in English. Two main areas were reviewed for OA biomarker studies: (1) an overview of disease-specific markers detected from different types of OA bio-samples, and (2) an up-to-date summary of the tissue-specific OA studies that have utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI). Overall, these OA biomarkers could provide clinicians with information for better the diagnosis, and prognosis of individual patients, and ultimately help facilitate the development of disease-modifying treatments.
Topics: Biomarkers; Cartilage, Articular; Humans; Osteoarthritis; Proteome; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Synovial Membrane
PubMed: 32899238
DOI: 10.3390/ijms21176414 -
Clinical and Experimental Immunology Feb 2019Osteoarthritis (OA) is the most common joint disease that strongly reduces the quality of life in patients; However, no disease-modifying therapy is available. For a... (Review)
Review
Osteoarthritis (OA) is the most common joint disease that strongly reduces the quality of life in patients; However, no disease-modifying therapy is available. For a long time, OA was considered a non-inflammatory disease that was the result of 'wear-and-tear' and abnormal mechanics, and therefore many considered the term 'osteoarthritis' a misnomer. However, during the last decades the notion arose that inflammation is not only present in the majority of OA patients but, rather, actively involved in the progression of the disease. Influx of immune cells is observed in the synovium and a plethora of inflammatory mediators is present in tissues and fluids from OA patients. These mediators cause the production of degrading enzymes that break down the cartilage matrix, which is the main hallmark of OA. Alarmins, which belong to the group of danger signals, have been implicated in many inflammatory diseases. They are among the first factors to be released upon cell stress due to, for example, infection, damage and inflammation. They attract and activate cells of the immune system and therefore lie at the base of the inflammatory reaction. In this narrative review, an overview of the history of OA, the evolving concept of inflammation as important factor in the OA pathogenesis, and particularly the central role that alarmins play in the initiation and maintenance of the low-grade inflammatory response in OA, is provided. Moreover, the targeting of alarmins as a promising approach to dampen the inflammation in OA is highlighted.
Topics: Alarmins; Humans; Inflammation; Osteoarthritis; Synovial Fluid; Synovial Membrane
PubMed: 30421798
DOI: 10.1111/cei.13237 -
Orthopaedics & Traumatology, Surgery &... Dec 2021The superior part of the glenohumeral joint capsule has an intimate relationship with the tendons of the rotator cuff and the tendon of the long head of the biceps. One...
INTRODUCTION
The superior part of the glenohumeral joint capsule has an intimate relationship with the tendons of the rotator cuff and the tendon of the long head of the biceps. One of the strategies currently proposed in the event of a massive cuff rupture is to reconstruct this superior capsule. The main objective of this anatomical study was to describe the superior joint capsule of the embryonic glenohumeral joint and its relationship to the tendons of the rotator cuff.
HYPOTHESIS
The hypothesis was that this structure was an anatomical entity, morphologically identifiable from the embryogenesis of the joint (more pronounced tissue boundaries in the fetus).
MATERIAL AND METHODS
In total, 101 continuous fetal anatomical sections (4 fetuses of 336mm), in the frontal plane, made it possible to identify and measure: diameters of the humeral head and glenoid, dimensions of the joint capsule insertion zone at the level of the greater tubercle, as well as the different thicknesses of this insertion zone. The ratios above the head of the biceps and against the superior labrum were also measured.
RESULTS
At the level of its distal insertion on the greater tuberosity, the thickness of the superior joint capsule varies on average between 0.8mm laterally and 1.2mm next to the tendons of the supraspinatus and infraspinatus; the thickness is 0.9mm next to the middle part of the supraspinatus tendon (the "rotator cable" zone). For its insertion at the level of the glenoid labrum, the superior capsule measures 0.6mm thick on average. The capsule around the tendon of the long head of the biceps is 1.5mm thick on average.
DISCUSSION
Here, we confirm the existence of this superior joint capsule, which can potentially be reconstructed. It is inserted on the greater tubercle covering 30 to 60% of its surface with variations in thickness. The joint capsule is fused to the supraspinatus tendon at the rotator cuff insertion area, preventing independent reinsertion of the tendon.
LEVEL OF EVIDENCE
IV; anatomical study.
Topics: Cadaver; Fetus; Humans; Humeral Head; Joint Capsule; Rotator Cuff; Rotator Cuff Injuries; Shoulder Joint
PubMed: 34562650
DOI: 10.1016/j.otsr.2021.103073 -
Acta Orthopaedica Et Traumatologica... May 2022The aim of the study was to assess the relationship between the expression of elastin, collagen type I, II,III and the degenera- tion of the facet joint capsule and the...
OBJECTIVE
The aim of the study was to assess the relationship between the expression of elastin, collagen type I, II,III and the degenera- tion of the facet joint capsule and the ligamentum flavum.
METHODS
10 patients (4 male, 6 female) (mean age 61 ± 14,9) undergoing surgery for degenerative lumbar spine syndrome and 5 cadav- ers (3 male, 2 female) (age of death 87 ± 8,6 years) were included in this study. One set of tissue samples was taken from each patient in the patient group intraoperatively and two sets of samples were taken from each cadaver in the cadaver group posthumosly from the ligamentum flavum (medial and lateral) and from the facet joint capsules (superior and inferior articular process) at the L4/5 segment. Western blot analysis was performed for collagen types I, II, III and for elastin. Disc degeneration was scored according to the Pfirmann Classification, facet joint arthrosis was scored according to the Fujiwara Classification and their relationship with protein expression was investigated.
RESULTS
There was a strong expression of Collagen type I in the patient group (PG) compared to the body donor group (BDG) in the facet joint capsule (FJC) and in the lateral samples of the ligamentum flavum. Samples of the FJC showed lower expression of elastin in the PG compared with the BDG, but without statistical significance. An increased expression of collagen type I compared to elastin in the PG could be shown. In contrast, elastin predominated in the samples of the BDG group compared to collagen type I (collagen type I/ elastin PG: PAsup 2,78; PAinf 2,61; LFmed 2,23; 225 LFlat 1,83; BDG: PAsup 0,15; PAinf 0,2; LFmed 0,2; LFlat 0,27). Rank correlation coefficient according to Spearman showed low to moderate correlations for collagen type I, III and elastin for the degree of disc degeneration accord- ing to Pfirrmann and the degree of facet joint osteoarthritis according to Fujiwara, all of them without statistical significance.
CONCLUSION
This study has shown us that in the context of degenerative changes of the lumbar spine, there is an increased expression of collagen type I and a dominance over elastin.
LEVEL OF EVIDENCE
Level III, Diagnostic Study.
Topics: Aged, 80 and over; Cadaver; Collagen; Collagen Type I; Elastin; Female; Humans; Intervertebral Disc Degeneration; Joint Capsule; Ligamentum Flavum; Lumbar Vertebrae; Male; Middle Aged; Zygapophyseal Joint
PubMed: 35703510
DOI: 10.5152/j.aott.2022.21314 -
Current Opinion in Rheumatology May 2015Evidence accumulated since 2010 indicates that human osteoarthritis should now be reclassified as a systemic musculoskeletal disease rather than a focal disorder of... (Review)
Review
PURPOSE OF REVIEW
Evidence accumulated since 2010 indicates that human osteoarthritis should now be reclassified as a systemic musculoskeletal disease rather than a focal disorder of synovial joints.
RECENT FINDINGS
Inflammation was seen as the key component promoting synovitis as well as progression of cartilage and bone destruction in osteoarthritis. Thus, metabolic-triggered inflammation involving cytokines, adipokines, abnormal metabolites, acute phase reactants and even complement, all appear to play major roles in osteoarthritis pathophysiology. Immune-mediated inflammation involving T cells and B cells as well as macrophages is now considered a common finding in osteoarthritis synovial tissue. Many experimental and clinical analyses showed that the proinflammatory cytokines, which stimulate matrix metalloproteinase and a disintegrin and metalloproteinase with thrombospondin motif gene transcription in normal and osteoarthritis human chondrocyte cultures, are also present at significantly elevated levels in the synovial fluid of osteoarthritis patients compared with nonarthritic synovial fluids.
SUMMARY
Human osteoarthritis is a systemic musculoskeletal disorder involving activation of innate and adaptive immune systems accompanied by inflammation exemplified by the elevated production of proinflammatory cytokines, which play a significant role in the progression of the disease. The future of novel therapies for osteoarthritis should consider developing drug development strategies designed to inhibit proinflammatory cytokine-induced signal transduction. These strategies have been successful in the development of drugs for the treatment of rheumatoid arthritis.
Topics: Humans; Inflammation Mediators; Osteoarthritis; Synovial Membrane
PubMed: 25784380
DOI: 10.1097/BOR.0000000000000162 -
Bone Research Feb 2024Osteoarthritis (OA) is a debilitating degenerative disease affecting multiple joint tissues, including cartilage, bone, synovium, and adipose tissues. OA presents... (Review)
Review
Osteoarthritis (OA) is a debilitating degenerative disease affecting multiple joint tissues, including cartilage, bone, synovium, and adipose tissues. OA presents diverse clinical phenotypes and distinct molecular endotypes, including inflammatory, metabolic, mechanical, genetic, and synovial variants. Consequently, innovative technologies are needed to support the development of effective diagnostic and precision therapeutic approaches. Traditional analysis of bulk OA tissue extracts has limitations due to technical constraints, causing challenges in the differentiation between various physiological and pathological phenotypes in joint tissues. This issue has led to standardization difficulties and hindered the success of clinical trials. Gaining insights into the spatial variations of the cellular and molecular structures in OA tissues, encompassing DNA, RNA, metabolites, and proteins, as well as their chemical properties, elemental composition, and mechanical attributes, can contribute to a more comprehensive understanding of the disease subtypes. Spatially resolved biology enables biologists to investigate cells within the context of their tissue microenvironment, providing a more holistic view of cellular function. Recent advances in innovative spatial biology techniques now allow intact tissue sections to be examined using various -omics lenses, such as genomics, transcriptomics, proteomics, and metabolomics, with spatial data. This fusion of approaches provides researchers with critical insights into the molecular composition and functions of the cells and tissues at precise spatial coordinates. Furthermore, advanced imaging techniques, including high-resolution microscopy, hyperspectral imaging, and mass spectrometry imaging, enable the visualization and analysis of the spatial distribution of biomolecules, cells, and tissues. Linking these molecular imaging outputs to conventional tissue histology can facilitate a more comprehensive characterization of disease phenotypes. This review summarizes the recent advancements in the molecular imaging modalities and methodologies for in-depth spatial analysis. It explores their applications, challenges, and potential opportunities in the field of OA. Additionally, this review provides a perspective on the potential research directions for these contemporary approaches that can meet the requirements of clinical diagnoses and the establishment of therapeutic targets for OA.
Topics: Humans; Osteoarthritis; Synovial Membrane; Metabolomics; Phenotype; Proteomics
PubMed: 38311627
DOI: 10.1038/s41413-023-00304-6 -
Journal of Orthopaedic Research :... Mar 2020Joint stiffness due to fibrosis/capsule contracture is a seriously disabling complication of articular injury that surgical interventions often fail to completely...
Joint stiffness due to fibrosis/capsule contracture is a seriously disabling complication of articular injury that surgical interventions often fail to completely resolve. Fibrosis/contracture is associated with the abnormal persistence of myofibroblasts, which over-produce and contract collagen matrices. We hypothesized that intra-articular therapy with drugs targeting myofibroblast survival (sulfasalazine), or collagen production (β-aminopropionitrile and cis-hydroxyproline), would reduce joint stiffness in a rabbit model of fibrosis/contracture. Drugs were encapsulated in poly[lactic-co-glycolic] acid pellets and implanted in joints after fibrosis/contracture induction. Capsule α-smooth muscle actin (α-SMA) expression and intimal thickness were evaluated by immunohistochemistry and histomorphometry, respectively. Joint stiffness was quantified by flexion-extension testing. Drawer tests were employed to determine if the drugs induced cruciate ligament laxity. Joint capsule fibroblasts were tested in vitro for contractile activity and α-SMA expression. Stiffness in immobilized joints treated with blank pellets (control) was significantly higher than in non-immobilized, untreated joints (normal) (p = 0.0008), and higher than in immobilized joints treated with sulfasalazine (p = 0.0065). None of the drugs caused significant cruciate ligament laxity. Intimal thickness was significantly lower than control in the normal and sulfasalazine-treated groups (p = 0.010 and 0.025, respectively). Contractile activity in the cells from controls was significantly increased versus normal (p = 0.001). Sulfasalazine and β-aminopropionitrile significantly inhibited this effect (p = 0.005 and 0.0006, respectively). α-SMA expression was significantly higher in control versus normal (p = 0.0021) and versus sulfasalazine (p = 0.0007). These findings support the conclusion that sulfasalazine reduced stiffness by clearing myofibroblasts from fibrotic joints. Statement of clinical significance: The results provide proof-of-concept that established joint stiffness can be resolved non-surgically. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:629-638, 2020.
Topics: Aminopropionitrile; Animals; Collagen; Contracture; Disease Models, Animal; Fibrosis; Hydroxyproline; Joint Capsule; Joint Diseases; Male; Muscle Contraction; Myofibroblasts; Rabbits; Stress, Mechanical; Sulfasalazine
PubMed: 31692083
DOI: 10.1002/jor.24499 -
Journal of Orthopaedic Research :... Nov 2021This study aimed to quantify the long-term progression of blunt and sharp cartilage defects and their effect on joint homeostasis and function of the equine carpus. In...
This study aimed to quantify the long-term progression of blunt and sharp cartilage defects and their effect on joint homeostasis and function of the equine carpus. In nine adult Shetland ponies, the cartilage in the radiocarpal and middle carpal joint of one front limb was grooved (blunt or sharp randomized). The ponies were subjected to an 8-week exercise protocol and euthanized at 39 weeks. Structural and compositional alterations in joint tissues were evaluated in vivo using serial radiographs, synovial biopsies, and synovial fluid samples. Joint function was monitored by quantitative gait analysis. Macroscopic, microscopic, and biomechanical evaluation of the cartilage and assessment of subchondral bone parameters were performed ex vivo. Grooved cartilage showed higher OARSI microscopy scores than the contra-lateral sham-operated controls (p < 0.0001). Blunt-grooved cartilage scored higher than sharp-grooved cartilage (p = 0.007) and fixed charge density around these grooves was lower (p = 0.006). Equilibrium and instantaneous moduli trended lower in grooved cartilage than their controls (significant for radiocarpal joints). Changes in other tissues included a threefold to sevenfold change in interleukin-6 expression in synovium from grooved joints at week 23 (p = 0.042) and an increased CPII/C2C ratio in synovial fluid extracted from blunt-grooved joints at week 35 (p = 0.010). Gait analysis outcome revealed mild, gradually increasing lameness. In conclusion, blunt and, to a lesser extent, sharp grooves in combination with a period of moderate exercise, lead to mild degeneration in equine carpal cartilage over a 9-month period, but the effect on overall joint health remains limited.
Topics: Animals; Carpal Joints; Cartilage Diseases; Cartilage, Articular; Horse Diseases; Horses; Synovial Fluid; Synovial Membrane
PubMed: 33368588
DOI: 10.1002/jor.24971 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2019This observational study was conducted to evaluate the anatomic relationship between the proximocaudal femoral joint capsule insertion and the femoral caudolateral...
This observational study was conducted to evaluate the anatomic relationship between the proximocaudal femoral joint capsule insertion and the femoral caudolateral curvilinear osteophyte (CCO), across ancient and modern domestic and non-domestic canids. Museum specimens of proximal femora were screened for presence of remnant enthesophytes of the caudal joint capsule insertion (first inclusion criterion) and then for the CCO (second inclusion criterion). The initially screened population included 267 dry bone specimens: Six Canis species, hybrid coyote × domestic dog, and five vulpines (three Vulpes species, one Urocyon, and one Nyctereutes). Proximocaudal joint capsule insertion remnant enthesophytes were limiting at n = 19 specimens: Seven ancient domestic dogs, four modern coyotes, two ancient coyotes, two modern hybrid coyote × dog, two modern red foxes, and two modern raccoon dogs. The joint capsule enthesophytes are associated with inflammation, but are observed far less frequently than the CCO. The CCO is seen radiographically but is visible more frequently by direct inspection. The primary inclusion criterion necessarily was a visible caudal joint capsule insertion; spatial relationships of the CCO can be assigned with confidence only when a capsule insertion line can be recognized clearly. We demonstrate that the anatomic CCO associates with the joint capsule insertion being nonspecific and species-independent. A joint capsule insertion-CCO spatial relationship across species is an important new observation, strongly indicating that both are pathological features. Our data indicate need for new research to characterize the canid coxofemoral joint and its overt and incipient pathology in a phylogenetic context. Anat Rec, 302:2164-2170, 2019. © 2019 American Association for Anatomy.
Topics: Animals; Coyotes; Dogs; Femur; Foxes; Hip Joint; Joint Capsule
PubMed: 31433562
DOI: 10.1002/ar.24231 -
Pediatric Rheumatology Online Journal Jan 2017The usefulness of musculoskeletal ultrasonography (MSUS) in paediatric population is limited by lack of reference values. One of such parameters is hip joint capsule...
BACKGROUND
The usefulness of musculoskeletal ultrasonography (MSUS) in paediatric population is limited by lack of reference values. One of such parameters is hip joint capsule thickness, postulated as an early measure for synovitis. However, the joint capsule is hardly a distinguished structure from slit synovial cavity in patients with little or no fluid collection. Therefore, in patients without effusion, it is more convenient to measure hip joint capsule thickness together with synovial cavity. The aim of the study was to establish percentile chart for hip joint capsule and synovial cavity thickness (HJC&SCT) in apparently healthy children.
MATERIAL AND METHODS
The analysis included 816 US of hip joint in 408 children without musculoskeletal disorders, distributed equally throughout the whole developmental period in 18 one-year subgroups. Hip joints US was performed according to standard protocol including measurement of HJC&SCT in a single rheumatology centre by three investigators.
RESULTS
The 3rd, 10th, 25th, 50th, 75th, 90th, and 97th HJC&SCT percentile curves were depicted in the age and height charts for the combined group of girls and boys. The median HJC&SCT values were increasing with age from 3.7 (C10 - C90: 3.3 - 4.2) mm in the first year of life up to 6.7 (5.8 - 7.3) in 16 years old, and above. In a similar way the increase was seen with height from 3.9 (3.5 - 4.7) mm in shorter than 95 cm to 6.9 (6.2 - 7.4) mm in taller than 169 cm subjects. Intra-observer and inter-observer mean precision was less than 1.8 and 12.5%, respectively.
CONCLUSION
The developed centile chart for hip joint capsule and synovial cavity thickness in the paediatric population is expected to improve detection of hip joint capsule disorders, including synovitis in juvenile idiopathic arthritis.
Topics: Adolescent; Child; Child Development; Child, Preschool; Female; Hip Joint; Humans; Joint Capsule; Male; Observer Variation; Reference Values; Regression Analysis; Ultrasonography
PubMed: 28143500
DOI: 10.1186/s12969-017-0136-6