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Current Opinion in Rheumatology Jul 2023To summarize recently discovered novel cell states in rheumatoid arthritis (RA) synovium that could have important implications for disease treatment. (Review)
Review
PURPOSE OF REVIEW
To summarize recently discovered novel cell states in rheumatoid arthritis (RA) synovium that could have important implications for disease treatment.
RECENT FINDINGS
The use of multiomic technologies, including single-cell and spatial transcriptomics and mass cytometry, has led to the discovery of several novel cell states, which could have important implications for the treatment of RA. These cells can be found in patient blood, synovial fluid, or synovial tissue and span several immune cell subsets as well as stromal cell types. These diverse cell states may represent the targets of current or future therapeutics, while their fluctuations may inform the ideal timing for therapy. Future efforts are needed to implicate how each cell state functions in the pathophysiologic network within affected joints and how medications perturb each cell state and ultimately the tissue.
SUMMARY
Multiomic molecular technologies have afforded the discovery of numerous novel cellular states in RA synovium; the next challenge will be to link these states to pathophysiology and treatment response.
Topics: Humans; Arthritis, Rheumatoid; Synovial Membrane; Synovial Fluid; Stromal Cells
PubMed: 37040654
DOI: 10.1097/BOR.0000000000000940 -
Frontiers in Immunology 2022Synovial inflammation in knee osteoarthritis (OA) causes disorganized synovial angiogenesis and complement activation in synovial fluid, but links between complement and...
PURPOSE
Synovial inflammation in knee osteoarthritis (OA) causes disorganized synovial angiogenesis and complement activation in synovial fluid, but links between complement and synovial microvascular pathology have not been established. Since complement causes vascular pathology in other diseases and since sex-differences exist in complement activation and in OA, we investigated sex differences in synovial fluid complement factors, synovial tissue vascular pathology, and associations between complement and synovial vascular pathology in patients with late-stage knee OA.
METHODS
Patients with symptomatic, late-stage radiographic knee OA undergoing total knee arthroplasty or high tibial osteotomy provided matched synovial fluid and tissue biopsies during surgery. Complement factors (C2, C5, adipsin, MBL, and CFI) and terminal complement complex (sC5b-C9) were measured in synovial fluid by multiplex or enzyme-linked immunosorbent assay, respectively. Features of synovial vascular pathology (vascularization, perivascular edema, and vasculopathy) were assessed by histopathology. Multivariate linear regression models were used to assess associations between synovial fluid complement factors and histopathological features of vascular pathology, with adjustment for age, sex, body mass index, and sex interaction. Sex-disaggregated comparisons were completed.
RESULTS
Synovial fluid biomarker and histopathology data were included from 97 patients. Most synovial fluid complement factors and synovial tissue histopathological features were similar between sexes. Synovial fluid C5 trended to lower levels in males (-20.93 ng/mL [95%CI -42.08, 0.23] 0.05). Median vasculopathy scores (0.42 [95%CI 0.07, 0.77] 0.02) were higher in males. In the full cohort, C5 concentration was associated with lower vascularization scores (-0.005 [95%CI -0.010, -0.0001] 0.04) while accounting for sex*C5 interaction. In sex-disaggregated analyses, increased C5 concentration was associated with lower vascularization scores (-0.005 [95%CI -0.009, -0.0001] 0.04) in male patients, but not in female patients. Males had higher sC5b-C9 compared to females. Additionally, males with high C5 had a higher synovial fluid concentration of sC5b-C9 compared to males with low C5. No differences were found in females.
CONCLUSION
Higher synovial fluid C5 levels were associated with increased complement activation and decreased synovial vascularization in males but not in females with OA. Future studies should test whether synovial fluid complement activation suppresses synovial angiogenesis and identify mechanisms accounting for C5-related sex-differences in synovial fluid complement activation in patients with knee OA.
Topics: Complement Activation; Female; Humans; Male; Osteoarthritis, Knee; Sex Characteristics; Synovial Fluid; Synovial Membrane
PubMed: 35686134
DOI: 10.3389/fimmu.2022.890094 -
The Bone & Joint Journal Sep 2016A variety of operative techniques have been described as under the term 'Bristow-Latarjet' procedure. This review aims to define the original procedure, and compare the... (Comparative Study)
Comparative Study Review
OBJECTIVES
A variety of operative techniques have been described as under the term 'Bristow-Latarjet' procedure. This review aims to define the original procedure, and compare the variation in techniques described in the literature, assessing any effect on clinical outcomes.
MATERIALS AND METHODS
A systematic review of 24 studies was performed to compare specific steps of the technique (coracoid osteotomy site, subscapularis approach, orientation and position of coracoid graft fixation and fixation method, additional labral and capsular repair) and detect any effect this variability had on outcomes.
RESULTS
Overall recurrence rate was 5.36% (2.94% to 43%). Half of the studies performed the procedure for recurrent shoulder instability, with only five studies documenting glenoid bone loss as an indication: 12 studies used the procedure as the primary surgical intervention for recurrent instability. No change in outcome was noted when examining variation in the coracoid osteotomy site, the fixation site on the scapular neck, the fixation method or whether a capsular repair was also performed. Performing a horizontal split in subscapularis may preserve external rotation compared with performing a tenotomy.
CONCLUSIONS
This is the first review to examine various operative techniques of the Bristow-Latarjet procedure, and their effect on outcome. We found that other than the approach through subscapularis, outcome was independent of the surgical technique, and depended more on patient selection. We would commend future publications on this procedure to provide a detailed description of the surgical technique, and as a minimum present rates of recurrence as an outcome measure. Cite this article: Bone Joint J 2016;98-B:1208-14.
Topics: Adult; Arthroscopy; Bone Screws; Female; Humans; Joint Capsule; Joint Instability; Male; Orthopedic Procedures; Osteotomy; Pain Measurement; Patient Selection; Prognosis; Range of Motion, Articular; Recurrence; Risk Assessment; Shoulder Dislocation; Young Adult
PubMed: 27587522
DOI: 10.1302/0301-620X.98B9.37948 -
PloS One 2016The natural history of rotator cuff tears can be unfavorable as patients develop fatty infiltration and muscle atrophy that is often associated with a loss of muscle...
BACKGROUND
The natural history of rotator cuff tears can be unfavorable as patients develop fatty infiltration and muscle atrophy that is often associated with a loss of muscle strength and shoulder function. To facilitate study of possible biologic mechanisms involved in early degenerative changes to rotator cuff muscle and tendon tissues, the objective of this study was to develop a joint capsule injury model in the canine shoulder using arthroscopy.
METHODS
Arthroscopic surgical methods for performing a posterior joint capsulectomy in the canine shoulder were first defined in cadavers. Subsequently, one canine subject underwent bilateral shoulder joint capsulectomy using arthroscopy, arthroscopic surveillance at 2, 4 and 8 weeks, and gross and histologic examination of the joint at 10 weeks.
RESULTS
The canine subject was weight-bearing within eight hours after index and follow-up surgeries and had no significant soft tissue swelling of the shoulder girdle or gross lameness. Chronic synovitis and macroscopic and microscopic evidence of pathologic changes to the rotator cuff bony insertions, tendons, myotendinous junctions and muscles were observed.
CONCLUSIONS
This study demonstrates feasibility and proof-of-concept for a joint capsule injury model in the canine shoulder. Future work is needed to define the observed pathologic changes and their role in the progression of rotator cuff disease. Ultimately, better understanding of the biologic mechanisms of early progression of rotator cuff disease may lead to clinical interventions to halt or slow this process and avoid the more advanced and often irreversible conditions of large tendon tears with muscle fatty atrophy.
Topics: Animals; Arthroscopy; Disease Models, Animal; Dogs; Female; Joint Capsule; Joint Diseases; Shoulder Joint
PubMed: 26808837
DOI: 10.1371/journal.pone.0147949 -
Clinical Anatomy (New York, N.Y.) Nov 2021The zona orbicularis, which comprises the inner circular fibers of the joint capsule, is vital for hip stability in distraction. Despite the proximity of the whole joint...
The zona orbicularis, which comprises the inner circular fibers of the joint capsule, is vital for hip stability in distraction. Despite the proximity of the whole joint capsule to the zona orbicularis, their anatomical relationship remains unclear. The aim of this study is to investigate the characteristics of the inner side of the joint capsule comprehensively. Twelve hips from nine bodies donated to science were examined. Six and three of the donated bodies, respectively, were embalmed using 8% formalin and Thiel's method. The joint capsules in three formalin-embalmed bodies were sturied by micro-computed tomography. During formalin fixation of six hips from these three bodies, one side was maintained at hip extension and the other at flexion. The remaining three formalin-embalmed bodies were examined histologically. Micro-computed tomography images revealed that the inward protrusion of the joint capsule narrowed the articular cavity, and the ratio of its narrowest area to that of the femoral neck was less at hip extension than at hip flexion. The Thiel's method specimens showed that the inner surface of the joint capsule protruded inward toward the femoral neck during hip extension. This inward protrusion was not histologically independent of the joint capsule. The zona orbicularis was interpreted as the inward protrusion caused by dynamic change of the joint capsule, rather than the local collar. In other words, the joint capsule could change its morphology dynamically depending on the hip position.
Topics: Aged; Aged, 80 and over; Cadaver; Female; Hip Joint; Humans; Joint Capsule; Male; Middle Aged; X-Ray Microtomography
PubMed: 34309921
DOI: 10.1002/ca.23767 -
The Anatomical Record Mar 1998The capsule of the proximal interphalangeal joint consists of the central slip of the extensor tendon dorsally, the collateral ligaments at the sides and the palmar...
BACKGROUND
The capsule of the proximal interphalangeal joint consists of the central slip of the extensor tendon dorsally, the collateral ligaments at the sides and the palmar ligament ventrally. Fibrocartilaginous menisci have been reported extending into the joint cavity and the central slip has a sesamoid fibrocartilage articulating with the proximal phalanx. This study relates ECM composition in the joint capsule to function.
METHODS
Each part of the capsule from 24 fingers amputated because of trauma, carcinoma, isthaemia, fixed-flexion deformities or Dupuytren's contracture, was dissected out. Sections were prepared for routine histology or immunolabelled with a panel of monoclonal and polyclonal antibodies against collagens and glycosaminoglycans using the avidin/biotin/peroxidase procedure.
RESULTS
All parts of the capsule consistently labelled for types I, III and VI collagens and for dermatan and keratan sulphate, though labelling was more pericellular in fibrocartilaginous regions. In contrast, only certain regions of the capsule in some fingers labelled for type II collagen, chondroitin 4 or 6 sulphate. The sesamoid fibrocartilage in the central slip showed the greatest degree of fibrocartilage differentiation, especially in fixed-flexion deformity fingers, and the palmar ligament the least.
CONCLUSIONS
The immunolabelling patterns suggest that there is an ordered sequence of matrix changes accompanying fibrocartilage differentiation. Chondroitin sulphate-containing proteoglycans accumulate first, and type II collagen appears later. The presence or absence of type II collagen probably relates to different levels of compressive loading. No fibrocartilaginous menisci were found in normal joints and those described previously are regarded as synovial folds.
Topics: Adolescent; Adult; Aged; Collagen; Finger Joint; Glycosaminoglycans; Humans; Immunohistochemistry; Joint Capsule; Ligaments, Articular; Male; Middle Aged; Tissue Distribution
PubMed: 9517845
DOI: 10.1002/(SICI)1097-0185(199803)250:3<281::AID-AR3>3.0.CO;2-3 -
The Journal of Bone and Joint Surgery.... Aug 2014Recurrent shoulder instability is commonly associated with glenoid bone defects. Coracoid transfer procedures, such as the Bristow and Latarjet procedures, are... (Comparative Study)
Comparative Study
BACKGROUND
Recurrent shoulder instability is commonly associated with glenoid bone defects. Coracoid transfer procedures, such as the Bristow and Latarjet procedures, are frequently used to address these bone deficiencies. Despite the frequent synonymous labeling of these transfers as the "Bristow-Latarjet" procedure, their true equivalence has not been demonstrated. Therefore, our purpose was to compare the biomechanical effects of these two procedures.
METHODS
Eight cadaveric specimens were tested on a custom shoulder simulator capable of loading nine muscle groups and of accurately orienting the joint throughout shoulder motion. The specimens were tested in the intact state, following Bristow and Latarjet reconstructions of a capsulolabral injury (0% glenoid defect), and following each procedure after creation of 15% and 30% glenoid bone defects. The reconstruction order was randomized. In each condition, joint stiffness (anterior stability) and occurrence of dislocation were assessed in shoulder adduction and abduction with neutral and external rotation.
RESULTS
No significant differences (p < 0.05) in joint stiffness or stability were found between the Bristow and Latarjet reconstructions for the 0% glenoid defect in any joint position. However, substantially greater joint stiffness occurred following the Latarjet procedure, as compared with the Bristow procedure, for the 15% and 30% glenoid bone-loss conditions in adduction with neutral rotation, adduction with external rotation, and abduction with external rotation (average across the three joint positions: 8.6 ± 4.4 N/mm versus 3.9 ± 1.26.7 N/mm [p = 0.034] with 15% bone loss and 7.5 ± 4.4 N/mm versus 3.4 ± 1.5 N/mm [p = 0.045] with 30% bone loss). The Latarjet reconstruction restored the stiffness that had been measured in the intact state in eleven of the twelve tested conditions, whereas the Bristow procedure was successful in only four of the twelve conditions. In addition, during instability testing, three more specimens dislocated following the Bristow reconstruction, compared with the Latarjet procedure, in the 15% defect condition and five more dislocated in the 30% defect condition.
CONCLUSIONS
The Bristow and Latarjet procedures are not equivalent in terms of their effects on glenohumeral joint stiffness and stability in cases of glenoid osseous deficiency.
CLINICAL RELEVANCE
The Bristow and Latarjet procedures have equivalent stabilizing effects in unstable shoulders with preserved glenoid osseous anatomy. However, the Latarjet procedure confers superior stabilization in the setting of substantial glenoid bone loss.
Topics: Aged; Analysis of Variance; Biomechanical Phenomena; Bone Transplantation; Cadaver; Humans; Joint Capsule; Joint Instability; Models, Anatomic; Range of Motion, Articular; Shoulder Dislocation; Shoulder Joint
PubMed: 25143494
DOI: 10.2106/JBJS.M.00627 -
Arthritis Research & Therapy Aug 2022Traumatic knee injuries in humans trigger an immediate increase in synovial fluid levels of inflammatory cytokines that accompany impact damage to joint tissues. We...
BACKGROUND
Traumatic knee injuries in humans trigger an immediate increase in synovial fluid levels of inflammatory cytokines that accompany impact damage to joint tissues. We developed a human in vitro cartilage-bone-synovium (CBS) coculture model to study the role of mechanical injury and inflammation in the initiation of post-traumatic osteoarthritis (PTOA)-like disease.
METHODS
Osteochondral plugs (cartilage-bone, CB) along with joint capsule synovium explants (S) were harvested from 25 cadaveric distal femurs from 16 human donors (Collin's grade 0-2, 23-83years). Two-week monocultures (cartilage (C), bone (B), synovium (S)) and cocultures (CB, CBS) were established. A PTOA-like disease group was initiated via coculture of synovium explants with mechanically impacted osteochondral plugs (CBS+INJ, peak stress 5MPa) with non-impacted CB as controls. Disease-like progression was assessed through analyses of changes in cell viability, inflammatory cytokines released to media (10-plex ELISA), tissue matrix degradation, and metabolomics profile.
RESULTS
Immediate increases in concentrations of a panel of inflammatory cytokines occurred in CBS+INJ and CBS cocultures and cultures with S alone (IL-1, IL-6, IL-8, and TNF-α among others). CBS+INJ and CBS also showed increased chondrocyte death compared to uninjured CB. The release of sulfated glycosaminoglycans (sGAG) and associated ARGS-aggrecan neoepitope fragments to the medium was significantly increased in CBS and CBS+INJ groups. Distinct metabolomics profiles were observed for C, B, and S monocultures, and metabolites related to inflammatory response in CBS versus CB (e.g., kynurenine, 1-methylnicotinamide, and hypoxanthine) were identified.
CONCLUSION
CBS and CBS+INJ models showed distinct cellular, inflammatory, and matrix-related alterations relevant to PTOA-like initiation/progression. The use of human knee tissues from donors that had no prior history of OA disease suggests the relevance of this model in highlighting the role of injury and inflammation in earliest stages of PTOA progression.
Topics: Cartilage, Articular; Cytokines; Humans; Inflammation; Osteoarthritis; Synovial Membrane
PubMed: 35982461
DOI: 10.1186/s13075-022-02881-z -
Scientific Reports Sep 2021Joint contracture leads to major patient discomfort. Metformin, one of the most extensively used oral drugs against type 2 diabetes has recently been found to suppress...
Joint contracture leads to major patient discomfort. Metformin, one of the most extensively used oral drugs against type 2 diabetes has recently been found to suppress tissue fibrosis as well. However, its role in suppressing tissue fibrosis in joint contractures remains unknown. In this study, we examined the role of metformin treatment in suppressing joint capsular fibrosis and the most effective time of its administration. Joint capsular fibrosis was induced by immobilizing the knee joints of mice using splints and tapes. Metformin was administered intraperitoneally every alternate day after immobilization. Histological and immunohistochemical changes and expression of fibrosis-related genes were evaluated. Metformin treatment significantly suppressed fibrosis in joint capsules based on histological and immunohistochemical evaluation. Joint capsular tissue from metformin-treated mice also showed decreased expression of fibrosis-related genes. Early, but not late, metformin administration showed the same effect on fibrosis suppression in joint capsule as the whole treatment period. The expression of fibrosis-related genes was most suppressed in mice administered with metformin early. These studies demonstrated that metformin treatment can suppress joint capsular fibrosis and the most effective time to administer it is early after joint immobilization; a delay of more than 2 weeks of administration is less effective.
Topics: Animals; Contracture; Disease Models, Animal; Fibrosis; Gene Expression; Immobilization; Immunohistochemistry; Injections, Intraperitoneal; Joint Capsule; Knee Joint; Male; Metformin; Mice; Mice, Inbred C57BL; Range of Motion, Articular; Time Factors; Transforming Growth Factor beta1; Treatment Outcome
PubMed: 34504209
DOI: 10.1038/s41598-021-97445-7 -
Spine Apr 2014Nonrandomized controlled cohort.
STUDY DESIGN
Nonrandomized controlled cohort.
OBJECTIVE
To characterize subaxial cervical facet joint kinematics and facet joint capsule (FJC) deformation during in vivo, dynamic flexion-extension. To assess the effect of single-level anterior arthrodesis on adjacent segment FJC deformation.
SUMMARY OF BACKGROUND DATA
The cervical facet joint has been identified as the most common source of neck pain, and it is thought to play a role in chronic neck pain related to whiplash injury. Our current knowledge of cervical facet joint kinematics is based on cadaveric mechanical testing.
METHODS
Fourteen asymptomatic controls and 9 C5-C6 arthrodesis patients performed full range of motion flexion-extension while biplane radiographs were collected at 30 Hz. A volumetric model-based tracking process determined 3-dimensional vertebral position with submillimeter accuracy. FJC fibers were modeled and grouped into anterior, lateral, posterior-lateral, posterior, and posterior-medial regions. FJC fiber deformations (total, shear, and compression-distraction) relative to the static position were determined for each cervical motion segment (C2-C3 through C6-C7) during flexion-extension.
RESULTS
No significant differences in the rate of fiber deformation in flexion were identified among motion segments (P = 0.159); however, significant differences were observed among fiber regions (P < 0.001). Significant differences in the rate of fiber deformation in extension were identified among motion segments (P < 0.001) and among fiber regions (P = 0.001). The rate of FJC deformation in extension adjacent to the arthrodesis was 45% less than that in corresponding motion segments in control subjects (P = 0.001).
CONCLUSION
In control subjects, FJC deformations are significantly different among vertebral levels and capsule regions when vertebrae are in an extended orientation. In a flexed orientation, FJC deformations are different only among capsule regions. Single-level anterior arthrodesis is associated with significantly less FJC deformation adjacent to the arthrodesis when the spine is in an extended orientation.
LEVEL OF EVIDENCE
4.
Topics: Adult; Biomechanical Phenomena; Case-Control Studies; Cervical Vertebrae; Female; Humans; Imaging, Three-Dimensional; Joint Capsule; Male; Middle Aged; Radiographic Image Interpretation, Computer-Assisted; Range of Motion, Articular; Spinal Diseases; Spinal Fusion; Tomography, X-Ray Computed; Treatment Outcome; Zygapophyseal Joint
PubMed: 24480943
DOI: 10.1097/BRS.0000000000000235