UNASSIGNED: This study aims to prove the healing results (regeneration) in cartilage defects using a combination treatment of microfractures and transplantation synovium-platelet rich fibrin (S-PRF).
UNASSIGNED: A cartilage defect was made in the trochlear groove of the knee of adult New Zealand white rabbits, and was classified into three treatment groups. The group 1 was cartilage defect without treatment, 2 with microfracture treatment, and 3 with microfracture covered with a synovium-platelet rich fibrin (S-PRF) membrane. Twelve weeks after the intervention, the animals were macroscopically and histologically examined, and evaluated by the International Cartilage Repair Society (ICRS). Additionally, the expression of aggrecan and type 2 collagen was examined by real-time-PCR.
UNASSIGNED: The ICSR scores for macroscopic were significantly higher in the microfracture and S-PRF transplant group than in the other groups. Also, the ICSR scores for histology were significantly higher in this group. The expression of aggrecan and type 2 collagen was higher in the group that received complete treatment.
UNASSIGNED: Microfractures and transplantation of synovium-platelet rich fibrin (S-PRF) can regenerate knee cartilage defects which have been shown to increase the expression of mRNA aggrecan and mRNA type 2 collagen resulting in excellent repair.

OBJECTIVE: The aim of this study was to investigate the presence of synovial mast cells (MCs) in hip and knee tissue from osteoarthritis (OA) patients and to correlate them with clinical and radiological data.
METHODS: Synovial tissue was obtained during arthroplasty from 60 patients, 30 with knee OA and 30 with hip OA. Control synovial tissue was obtained from 30 patients without OA, 15 undergoing above-knee amputation and 15 receiving a hip replacement for fracture. Before surgery, the radiographic findings were graded according to the Kellgren-Lawrence system and clinical data including pain (VAS) and functional information (KOOS and HOOS) was collected. The tissue was stained with hematoxylin-eosin and toluidine blue for histochemistry and incubated with CD117 and CD31 antibodies for immunohistochemistry. MC and vessel number and synovitis score were determined in all samples.
RESULTS: Mean MC number, synovitis score and vessel number were significantly higher in the OA samples (p < 0.05) than in control tissue. MC number correlated with the synovitis score and disease severity in both patient groups.
CONCLUSIONS: The prevalence of MCs in synovium from OA patients and their association with synovial inflammation and pain suggest a role for them in OA pathophysiology.

Shoulder bursae are essential for normal movement and are also implicated in the pathogenesis of shoulder pain and dysfunction. The subacromial bursa (SAB), within the subacromial space, is considered a primary source of shoulder pain. Several other bursae related to the subcoracoid space, including the coracobrachial (CBB), subcoracoid (SCB) and subtendinous bursa of subscapularis (SSB), are also clinically relevant. The detailed morphology and histological characteristics of these bursae are not well described. Sixteen embalmed cadaveric shoulders from eight individuals (five females, three males; mean age 78.6 ± 7.9 years) were investigated using macro-dissection and histological techniques to describe the locations, dimensions and attachments of the bursae, their relationship to surrounding structures and neurovascular supply. Bursal sections were stained with haematoxylin and eosin to examine the synovium and with antibodies against von Willebrand factor and neurofilament to identify blood vessels and neural structures respectively. Four separate bursae were related to the subacromial and subcoracoid spaces. The SAB was large, with a confluent subdeltoid portion in all except one specimen, which displayed a distinct subdeltoid bursa. The SAB roof attached to the lateral edge and deep surface of the acromion and coracoacromial ligament, and the subdeltoid fascia; its floor fused with the supraspinatus tendon and greater tubercle. The CBB (15/16 specimens) was deep to the conjoint tendon of coracobrachialis and short head of biceps brachii and the tip of the coracoid process, while the inconstant SCB (5/16 specimens) was deep to the coracoid process. Located deep to the subscapularis tendon, the SSB was a constant entity that commonly displayed a superior extension. Synovial tissue was predominantly areolar (SAB and SSB) or fibrous (CBB and SCB), with a higher proportion of areolar synovium in the bursal roofs compared to their floors. Blood vessels were consistently present in the subintima with a median density of 3% of the tissue surface area, being greatest in the SSB and SAB roofs (4.9% and 3.4% respectively) and least in the SAB floor (1.8%) and CBB roof and floor (both 1.6%). Nerve bundles and free nerve endings were identified in the subintima in approximately one-third of the samples, while encapsulated nerve endings were present in deeper tissue layers. The extensive expanse and attachments of the SAB support adoption of the term subacromial-subdeltoid bursa. Morphologically, the strong attachments of the bursal roofs and floors along with their free edges manifest as fixed and mobile portions, which enable movement in relation to surrounding structures. The presence of neurovascular structures demonstrates that these bursae potentially contribute blood supply to surrounding structures and are involved in mechanoreception. The anatomical details presented in this study clarify the morphology of the shoulder bursae, including histological findings that offer further insight into their potential function.

OBJECTIVE: Intermetatarsal bursitis (IMB) represents juxta-articular synovial inflammation of the intermetatarsal bursae. Recent MRI-studies identified IMB as feature of early RA, but whether IMB already occurs in the pre-arthritic phase is unknown. We performed a large MRI-study in clinically suspect arthralgia (CSA) to assess the occurrence and prognostic value of IMB.
METHODS: 577 consecutive CSA-patients underwent contrast-enhanced MRI of the forefoot, metacarpophalangeal joints and wrist. MRIs were evaluated for subclinical synovitis/tenosynovitis/osteitis in line with the RA MRI scoring system (summed as RAMRIS-inflammation) and for IMB. IMB was considered present if uncommon in the general population at the same location (i.e. size scored above the 95th-percentile in age-matched symptom-free controls). The relation of IMB with other MRI-detected subclinical inflammation synovitis/tenosynovitis/osteitis) was studied. Cox-regression assessed the association with clinical arthritis development during median 25 months follow-up. ACPA-stratification was performed.
RESULTS: At presentation with CSA, 23% had IMB. IMB was more frequent in ACPA-positive than ACPA-negative CSA (47% vs 19%,p< 0.001). Patients with IMB were more likely to also have subclinical synovitis (OR 3.4 (95%CI 1.8-6.5)) and tenosynovitis (5.9(2.8-12.6)). IMB conferred higher risk of developing arthritis (HR 1.6(1.0-2.7) adjusted for other subclinical inflammation). IMB-presence predicted arthritis development in ACPA-positive CSA (adjusted HR 2.2(1.0-4.7)), but not in ACPA-negative CSA-patients (0.8(0.4-1.7)).
CONCLUSIONS: Approximately a quarter of CSA-patients have IMB, which is frequently accompanied by subclinical synovitis and tenosynovitis. IMB precedes development of clinical arthritis, particularly in ACPA-positive CSA. These results reinforce the notion that juxta-articular synovial inflammation is involved in the earliest phases of RA-development.

UNASSIGNED: Shear-wave elastographic ultrasound (SW-EUS) assesses the stiffness of human tissues. It is used in liver, thyroid and breast imaging but has not been studied in synovium. Soft tissues have a slower shear-wave velocity (SWV) than stiff tissues. We hypothesised that rheumatoid arthritis (RA) patients would have softer synovium than controls and this could be quantified with a slower SWV. We also assessed whether SWV varied with disease activity.
UNASSIGNED: Nine patients with RA were consecutively recruited and matched with five controls. Participants underwent clinical assessment, blood sampling, grey scale ultrasound (GSUS), power Doppler ultrasound and SW-EUS of MCP joints 2-5 on the dominant hand.
UNASSIGNED: Average age was 60. Mean RA disease activity (DAS28-ESR) was moderate at 3.65. Patients with RA had lower maximum synovial SWV than controls (6.38 m/s vs. 6.99 m/s P = 0.042). Negative Pearson\'s correlation coefficients (PCC) were observed between maximum SWV and disease activity markers including GSUS graded synovial thickness (PCC = -0.57, P = 0.03) and ESR (PCC = -0.46, P = 0.095). Intra- and interobserver reliability was good with intraclass correlation coefficients (ICC) of 0.66 and 0.58, respectively, for quantitative maximum SWV and ICC > 0.80 for colour scale rated SWV.
UNASSIGNED: This is the first pilot study of SW-EUS in synovium. Maximum synovial SWV was significantly lower in RA than controls. There was a negative correlation between maximum SWV and GSUS synovial thickening. Further study is warranted to confirm the role of SW-EUS in diagnosing and assessing disease activity in RA.

UNASSIGNED: Synovium has been documented as a primary site of inflammation and a major effector organ in a variety of joint diseases. Study of simple technique like synovial biopsy can help in early diagnosis and treatment of diseases significantly improving outcome of patient in cases of rheumatoid arthritis, osteoarthritis, etc., Only limited data exist on utility of synovial biopsies.
UNASSIGNED: To analyze the pattern of synovial lesions to differentiate between different kinds of arthritis. Also, to identify early stages of arthritis so as to prevent unnecessary invasive surgical procedure.
UNASSIGNED: It\'s a retrospective study to analyze 103 cases of synovial lesions diagnosed in last five years at a tertiary care orthopedic center. All synovial biopsies obtained mainly by open method and few by arthroscopic method, that came to the Dept of Pathology were included. Lesions were classified into four categories that is, inflammatory joint diseases, degenerative joint diseases, tumor-like conditions and tumors.
UNASSIGNED: Age group most affected was between 61 and 70 years, with male predominance. Osteoarthritis (OA) was the most common histopathological diagnosis. Early OA tissues showed greater lining layer thickness, vessel proliferation, and inflammation, while surface fibrin deposition along with fibrosis was noted in later stages.
UNASSIGNED: The histo-morphological observations made in this study may have important therapeutic implications for some patients during the early evolution of arthritis and could prevent unnecessary operative intervention of later stages.

OBJECTIVE: The purpose of this study was to compare the potential effects of pedunculated and free synovial grafts in the repair of full-thickness articular cartilage defects on an animal model with histological and immunohistochemical analysis.
METHODS: A comparative study in an animal model was performed with 24 rabbits, divided into two groups. Full-thickness cartilage defects were created bilaterally on the knees of all rabbits. Pedunculated and free synovial grafts were applied to the right knees of Group 1 and Group 2, respectively. Left knees were left as the control group. Six rabbits from each group were randomly selected for euthanasia 4 and 8 weeks postoperatively. All samples were examined histologically with a cartilage scoring system. For immunohistochemical analysis, the degree of collagen 2 staining was determined using a staging system. All data were statistically compared between the study groups with Student\'s t-test or Mann-Whitney U-test. The correlations between categorical variables were analyzed with Fisher\'s exact test and Chi-square test.
RESULTS: In Group 1, the mean defect size had significantly decreased at 8 weeks postsurgery. It was also significantly smaller than that of Group 2. Both pedunculated and free synovial grafts had significantly better histological and immunohistochemical outcomes compared with the controls. Contrastingly, the results of comparison between the study groups (Group 1 vs. 2) at the 4th and 8th week were not statistically significant with regard to histological scores and immunohistochemical staining.
CONCLUSIONS: Synovial tissue, whether pedunculated or free, provided much better cartilage recovery compared with the control. It can be used as a mesenchymal stem cell (MSC) source, and synovium-derived MSCs have the chondrogenic potential for the in vivo treatment of full-thickness cartilage defects.

To identify biomarkers of treatment change and radiographic progression in patients with RA under remission.
RA patients in remission (DAS28-ESR <2.6) were selected and followed up for 5 years. An MRI of the dominant hand and an US assessment of knees/hands and serum levels of inflammation/angiogenesis biomarkers were performed at baseline and at 12th month. Synovial biopsies were obtained in patients with Power Doppler signal. Conventional radiographies of hands/feet were taken at baseline and after 5 years. Radiographic progression was defined as the change in the modified Sharp van der Heijde Score at 5 years >10.47 (small detectable change).
Sixty patients were included, 81.6% were ACPA+ and 45% were taking biological DMARDs. At baseline, 66.6% had Power Doppler signal. After 5 years, 73.3% of patients remained in remission. Change of therapy was performed in 20 patients (33.3%) and was associated with BMI [odds ratio (OR) 1.3, 95% CI: 1, 1.7], lack of biological DMARD therapy (OR 24.7, 95% CI: 2.3, 257.2), first-year progression of MRI erosions (OR 1.2, 95% CI: 1, 1.3) and calprotectin serum levels (OR 2.8, 95% CI: 1, 8.2). Radiographic progression occurred in six (10%) patients. These patients had higher first-year progression of MRI erosions (P =  0.03) and bone oedema (P = 0.04). Among 23 patients undergoing synovial biopsy, mast cell density was independently associated with clinical flares.
One-third of RA patients lost clinical remission and changed therapy throughout the 5 years of follow-up, which was independently associated with BMI, lack of biological DMARDs therapy and first-year progression of MRI erosion score and calprotectin serum levels. Significant radiographic progression was uncommon.

There is an increasing number of reports on the treatment of knee osteoarthritis (OA) using mesenchymal stem cells (MSCs). However, it is not known what would better drive osteoarthritis stabilization to postpone total knee arthroplasty (TKA): targeting the synovial fluid by injection or targeting on the subchondral bone with MSCs implantation.
A prospective randomized controlled clinical trial was carried out between 2000 and 2005 in 120 knees of 60 patients with painful bilateral knee osteoarthritis with a similar osteoarthritis grade. During the same anaesthesia, a bone marrow concentrate of 40 mL containing an average 5727 MSCs/mL (range 2740 to 7540) was divided in two equal parts: after randomization, one part (20 mL) was delivered to the subchondral bone of femur and tibia of one knee (subchondral group) and the other part was injected in the joint for the contralateral knee (intra-articular group). MSCs were counted as CFU-F (colony fibroblastic unit forming). Clinical outcomes of the patient (Knee Society score) were obtained along with radiological imaging outcomes (including MRIs) at two year follow-up. Subsequent revision surgeries were identified until the most recent follow-up (average of 15 years, range 13 to 18 years).
At two year follow-up, clinical and imaging (MRI) improvement was higher on the side that received cells in the subchondral bone. At the most recent follow-up (15 years), among the 60 knees treated with subchondral cell therapy, the yearly arthroplasty incidence was 1.3% per knee-year; for the 60 knees with intra-articular cell therapy, the yearly arthroplasty incidence was higher (p = 0.01) with an incidence of 4.6% per knee-year. For the side with subchondral cell therapy, 12 (20%) of 60 knees underwent TKA, while 42 (70%) of 60 knees underwent TKA on the side with intra-articular cell therapy. Among the 18 patients who had no subsequent surgery on both sides, all preferred the knee with subchondral cell therapy.
Implantation of MSCs in the subchondral bone of an osteoarthritic knee is more effective to postpone TKA than injection of the same intra-articular dose in the contralateral knee with the same grade of osteoarthritis.

During meniscal tissue repair, the origin of the reparative cells of damaged meniscal tissue remains unclear.
Comparison of the influence between meniscal and synovial tissues on meniscal repair by the in vivo freeze-thaw method would clarify the origin of meniscal reparative cells.
Controlled laboratory study.
A total of 48 mature Japanese white rabbits were divided into 4 groups according to the tissue (meniscal or synovial) that received freeze-thaw treatment. The meniscus of each group had a 2 mm-diameter cylindrical defect filled with alginate gel. Macroscopic and histologic evaluations of the reparative tissues were performed at 1, 3, and 6 weeks postoperatively. Additional postoperative measurements included cell density, which was the number of meniscal cells in the cut area per cut area (mm2) of meniscus; cell density ratio, which was the cell density of the sample from each group per the average cell density of the intact meniscus; and cell death rate, which was the number of cells stained by propidium iodide per the number of cells stained by Hoechst 33342 of the meniscal tissue adjacent to the defect.
The macroscopic and histologic evaluations of the non-synovium freeze-thaw groups were significantly superior to those of the synovium freeze-thaw groups at 3 and 6 weeks postoperatively. Additionally, the meniscal cell density ratio and cell death rate in the freeze-thaw groups were significantly lower than those in the non-meniscal freeze-thaw groups at 3 and 6 weeks postoperatively.
The freeze-thawed meniscus recovered few cells in its tissue even after 6 weeks. However, the defect was filled with fibrochondrocytes and proteoglycan when the synovium was intact. On the basis of these results, it is concluded that synovial cells are the primary contributors to meniscal injury repair.
In meniscal tissue engineering, there is no consensus on the best cell source for meniscal repair. Based on this study, increasing the synovial activity and contribution should be the main objective of meniscal tissue engineering. This study can establish the foundation for future meniscal tissue engineering.