CARTILAGE最新文献

ObjectiveTo compare substantial clinical benefit (SCB) of a hydrogel-based, matrix-associated autologous chondrocyte implantation (M-ACI) method versus microfracture (MFx) in the treatment of knee cartilage defects.DesignPropensity score matched-pair analysis, using the MFx control group of a phase III study as comparator for M-ACI treatment in a single-arm phase III study, resulting in 144 patients in the matched-pair set.ResultsGroups were comparable regarding baseline Knee Injury and Osteoarthritis Outcome Score (KOOS), sex, age, body mass index, symptom duration, smoking status, and previous knee surgeries. Defect sizes in the M-ACI group were significantly larger than in the MFx group (6.4 cm² vs. 3.7 cm²). Other differences concerned location, number, and etiology of defects that were not considered to influence the interpretation of results. At 24 months, significantly more patients in the M-ACI group achieved SCB in KOOS pain (72.2% vs. 48.6%; P = 0.0108), symptoms (84.7% vs. 61.1%, P = 0.0039), sports/recreation (84.7% vs. 56.9%, P = 0.0008), and quality of life (QoL; 72.2% vs. 44.4%, P = 0.0014). The SCBs for KOOS activities in daily living and International Knee Documentation Committee score were higher for M-ACI but not significantly different from MFx. The SCB rates consistently favored M-ACI from 3 months onward. The highest improvements from baseline at 24 months in patients with SCB were observed for KOOS sports/rec. (M-ACI: 60.8 points, MFx: 55.9 points) and QoL (M-ACI: 58.1, MFx: 57.4).ConclusionHydrogel-based M-ACI demonstrated superior SCB in KOOS pain, symptoms, sports/rec., and QoL compared with MFx in patients with knee cartilage defects through 2 years follow-up.

ObjectiveIntegrin α10β1-selected mesenchymal stem cells (integrin α10-MSCs) have previously shown potential in treating cartilage damage and osteoarthritis (OA) in vitro and in animal models in vivo. The aim of this study was to further investigate disease-modifying effects of integrin α10-MSCs.DesignOA was surgically induced in 17 horses. Eighteen days after surgery, horses received 2 × 10⁷ integrin α10-MSCs intra-articularly or were left untreated. Lameness and response to carpal flexion was assessed weekly along with synovial fluid (SF) analysis. On day 52 after treatment, horses were euthanized, and carpi were evaluated by computed tomography (CT), MRI, histology, and for macroscopic pathology and integrin α10-MSCs were traced in the joint tissues.ResultsLameness and response to carpal flexion significantly improved over time following integrin α10-MSC treatment. Treated horses had milder macroscopic cartilage pathology and lower cartilage histology scores than the untreated group. Prostaglandin E2 and interleukin-10 increased in the SF after integrin α10-MSC injection. Integrin α10-MSCs were found in SF from treated horses up to day 17 after treatment, and in the articular cartilage and subchondral bone from 5 of 8 treated horses after euthanasia at 52 days after treatment. The integrin α10-MSC injection did not cause joint flare.ConclusionThis study demonstrates that intra-articular (IA) injection of integrin α10-MSCs appears to be safe, alleviate pathological changes in the joint, and improve joint function in an equine post-traumatic osteoarthritis (PTOA) model. The results suggest that integrin α10-MSCs hold promise as a disease-modifying osteoarthritis drug (DMOAD).

Intra-articular injections of hyaluronic acid (HA) are widely used in the treatment of osteoarthritis. HA half-life varies between products which might explain differences in effectiveness between viscosupplements.AimTo compare the resistance to degradation of linear and cross-linked viscosupplements using a rheological model combining mechanical and oxidative stresses, mimicking what happens inside the joint following HA injection.MethodsThe rheological properties of 8 HAs were measured using a stress-imposed Rheometer DHR3. Strain sweeps were carried out to evaluate the rheological properties at rest from 0.001 to 3000% at a frequency of 1 Hz. The complex modulus G*, in Pa, and the phase tangent tan δ, dimensionless, in the linear viscoelastic domain (LVED) were extracted. The oxidation tests were conducted by exposing the product to H₂O₂ for 30 minutes. The effect of oxidation was evaluated by measuring variations of G* and tan δ, using an oscillation time sweep. Those tests were carried out at a frequency of 1 Hz and at 1% strain in the LVED.ResultsAt rest, the different samples exhibited various viscous behaviors. During mixing process, G* decreased from -6.4% to -31.3%. G* of low-molecular-weight HAs decreased more than that of medium molecular weight (MW) and cross-linked products. After oxidative stress, G* variation ranged from -10.1% to -46.3%. Cross-linked HAs and those containing mannitol resisted the best to degradation.ConclusionsWe showed large variations in resistance to degradation between viscosupplements. The duration of effectiveness of these products deserves to be compared in randomized clinical studies.

Objectivesα2-Macroglobulin (A2M) can prevent cartilage degeneration by blocking many types of cartilage-degrading enzymes, but the mechanism remains to be clarified. This study aimed to test that A2M protects against cartilage degeneration by promoting chondrocyte proliferation and cartilage matrix synthesis via inducing proliferating cell nuclear antigen (PCNA).DesignThe cartilage degeneration of the anterior cruciate ligament transection (ACLT) model was evaluated by Safranin O-fast green staining, and articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI)-modified Mankin criteria. The chondrocyte proliferation was detected by 5-Bromodeoxyuridinc (BrdU), MTT, and Cell Counting Kit-8 (CCK8) methods. The chondrocyte apoptosis was detected by lactate dehydrogenase (LDH) assay and Annexin PI staining with the flow cytometer. The glycosaminoglycan (sGAG) and aggrecan in culture supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to analyze the type II collagen and aggrecan mRNA expression. The PCNA protein expression was analyzed by western blot and immunofluorescent staining.ResultsA2M can attenuate cartilage degeneration in ACLT rats. The OARSI scores for cartilage degeneration in the A2M group were lower than those in the phosphate-buffered saline (PBS) group. A2M can promote chondrocyte proliferation and inhibit chondrocyte apoptosis, promote the cartilage matrix synthesis in chondrocytes (type II collagen and aggrecan), and culture supernatant (sGAG and aggrecan). At the same time, it also up-regulated the PCNA protein expression in chondrocytes.ConclusionsA2M can promote chondrocyte proliferation and cartilage matrix synthesis via inducing PCNA expression.

ObjectiveNewer all-suture, all-inside meniscus repair devices utilize soft suture anchors. The purpose of this study was to compare the biomechanical performance of 4 meniscus repair devices in human cadaver menisci: the JuggerStitch (all-suture, all-inside), the FiberStitch (all-suture, all-inside), a polyether ether ketone (PEEK) all-inside, and an inside-out device.DesignForty human cadaver menisci were tested after creating 20 mm longitudinal tears in the posterior meniscus. Each knee was randomized to 1 of 4 meniscus repair groups: JuggerStitch (all-suture, all-inside), FiberStitch (all-suture, all-inside), FAST-FIX 360 (PEEK-based anchor all-inside), and inside-out (with Broadband^TM tape meniscus needles). For each meniscus, 2 devices were used to prepare vertical mattress repair construct. The specimens were tested by pre-conditioning 20 cycles between 5 N and 30 N and then the tear diastasis was measured, followed by distraction to failure phase after imposing a displacement at a rate of 0.5 mm/s.ResultsTen menisci were tested in each of the 4 groups. After pre-conditioning, there was no significant difference in the gap formation among groups (P = 0.212). The average failure load for the JuggerStitch, FiberStitch, PEEK all-inside, and inside-out was 384 N, 311 N, 207 N, and 261 N, respectively, with a significant difference between groups (P = 0.034). Post hoc analysis showed the JuggerStitch failure load was higher than the PEEK all-inside and inside-out (P = 0.005, and P = 0.045, respectively). There was no significant difference between the failure load of the JuggerStitch and FiberStitch (P = 0.225).ConclusionThe JuggerStitch all-suture device, FiberStitch all-suture device, PEEK all-inside, and inside-out devices have similar biomechanical properties for gapping and stiffness. The JuggerStitch all-suture, all-inside device has superior failure load compared with the PEEK all-inside and inside-out repair for longitudinal meniscus tear repair.

ObjectiveThis study aimed to isolate and compare the mesenchymal stem cell characteristics of CD90⁺ cells from different fibrocartilage tissues in the temporomandibular joint (TMJ), the knee joint, and the intervertebral joint to further understand the similarities and differences of these 4 fibrocartilage tissues.MethodsCD90⁺ cells were isolated from TMJ disc, condylar cartilage, meniscus, and intervertebral disc by using magnetic-activated cell sorting. Cellular assays including 4.5-ethynyl-2'-deoxyuridine labeling, multilineage differentiation, colony formation, and cell migration were conducted to compare their mesenchymal stem cell characteristics. Immunofluorescent staining was performed for observing the expression of actively proliferating CD90⁺ cells within the tissues. H&E staining and Safranine O staining were used to compare the histological features.ResultsThe CD90⁺ cells derived from these 4 fibrocartilage tissues exhibited comparable cell proliferation abilities. However, the cells from the TMJ disc displayed limited multilineage differentiation potential, colony formation, and cell migration abilities in comparison with the cells from the other fibrocartilage tissues. In vivo, there was relatively more abundant expression of CD90⁺ cells in the TMJ disc during the early postnatal stage. The limited EDU⁺ cell numbers signified a low proliferation capacity of CD90⁺ cells in the TMJ disc. In addition, we observed a significant decrease in cell density and a restriction in the synthesis of extracellular proteoglycans in the TMJ disc.ConclusionOur study highlights the spatial heterogeneity of CD90⁺ cells in the fibrocartilages of different joint tissues, which may contribute to the limited cartilage repair capacity in the TMJ disc.

ObjectiveOsteochondral defects develop into osteoarthritis without intervention. Costal cartilage can be utilized as an alternative source for repairing osteochondral defect. Our previous clinical study has shown the successful osteochondral repair by costal cartilage graft with integration into host bone bed. In this study, we investigate how cartilaginous graft adapt to osteochondral environment and the mechanism of bone-cartilage interface formation.DesignCostal cartilage grafting was performed in C57BL/6J mice and full-thickness osteochondral defect was made as control. 3D optical profiles and micro-CT were applied to evaluate the reconstruction of articular cartilage surface and subchondral bone as well as gait analysis to evaluate articular function. Histological staining was performed at 2, 4, and 8 weeks after surgery. Moreover, costal cartilage from transgenic mice with fluorescent markers were transplanted into wild-type mice to observe the in vivo changes of costal chondrocytes.ResultsAt 8 weeks after surgery, 3D optical profiles and micro-CT showed that in the graft group, the articular surface and subchondral bone were well preserved. Gait analysis and International Cartilage Repair Society (ICRS) score evaluation showed a good recovery of joint function and histological repair in the graft group. Safranin O staining showed the gradual integration of graft and host tissue. Costal cartilage from transgenic mice with fluorescent markers showed that donor-derived costal chondrocytes turned into osteocytes in the subchondral area of host femur.ConclusionCostal cartilage grafting shows both functional and histological repair of osteochondral defect in mice. Graft-derived costal chondrocytes differentiate into osteocytes and contribute to endochondral ossification.

ObjectiveHyaluronic acid (HA) in synovial fluid (SF) contributes to boundary lubrication with altered levels in osteoarthritis (OA) and rheumatoid arthritis (RA). SF extracellular vesicles (EVs) may participate in arthritis by affecting inflammation and cartilage degradation. It remains unknown whether HA and EVs display joint-specific alterations in arthritic SFs.DesignWe investigated the numbers and characteristics of HA-particles and large EVs in SF from knees and shoulders of 8 OA and 8 RA patients and 8 trauma controls, and in plasma from 10 healthy controls and 11 knee OA patients. The plasma and SF HA concentrations were determined with a sandwich-type enzyme-linked sorbent assay, and EVs and HA-particles were characterized from plasma and unprocessed and centrifuged SFs with confocal microscopy. The data were compared according to diagnosis, location, and preanalytical processing.ResultsThe main findings were: (1) OA and RA SFs can be distinguished from trauma joints based on the distinctive profiles of HA-particles and large EVs, (2) there are differences in the SF HA and EV characteristics between shoulder and knee joints that could reflect their dissimilar mobility, weight-bearing, and shock absorption properties, (3) EV counts in SF and plasma can positively associate with pain parameters independent of age and body adiposity, and (4) low-speed centrifugation causes alterations in the features of HA-particles and EVs, complicating their examination in the original state.ConclusionsArthritis and anatomical location can affect the characteristics of HA-particles and large EVs that may have potential as biomarkers and effectors in joint degradation and pain.

Introduction. Bone marrow lesions (BMLs) are MRI-visible subchondral bone alterations, highly correlated with symptoms in the knee. Subchondroplasty (SCP) is able to fill the subchondral defects associated with BMLs using an injectable bone substitute material. The aim of the present study is to evaluate the 12-month outcomes of the SCP in the treatment of symptoms of mild-to-moderate knee osteoarthritis (OA) patients with persistent BMLs of the knee. Materials and Methods. Subjects affected by BMLs of the femoral condyle or tibial plateau that were present for >3 months and not responsive to conservative treatments were enrolled in this prospective multicenter trial. All the patients underwent SCP. Follow-up was conducted at 1, 3, 6 and 12 months. All subjects completed Numerical Rating Scale (NRS) for pain, Knee Injury and Osteoarthritis Outcome (KOOS) score, Euro Quality of life-5 dimensions (EQ-5D) score, and a subject global satisfaction scale. Demographic information of the patients was also collected. Results. A total of 79 patients completed the 12-month follow-up. Statistically significant improvements on all clinical scales were registered from baseline to the 12-month follow-up. No severe adverse events were reported. Four patients were considered failed. A 12-month subgroup analysis was performed to evaluate the possible correlation between all the KOOS subscales and age, gender, number of BMLs, location of BMLs, and Kellgren-Lawrence grade: no statistically significant associations were observed. Conclusion. SCP is a safe and effective procedure for the treatment of symptoms related to persisting BMLs in mild-to-moderate osteoarthritic knees, with a low failure rate up to 12 months' evaluation.

ObjectiveTo investigate how running, cycling, and sedentary cardiovascular stress impact biomarkers of cartilage turnover acutely in subjects with knee osteoarthritis (OA).DesignThis was a sequential, cross-over, clinical study. Forty subjects with primary knee OA underwent moderate-to-high-intensity cycling, running, and adrenaline infusion on separate days. Blood was sampled before, during, and at 6-time points after intervention. On a control day, similar samples were taken. Biomarkers of type II collagen degradation (C2M, T2CM, Coll2-1, Coll2-1NO2), formation (PRO-C2), and aggrecan degradation (ARGS) were measured.ResultsMean age was 60.4 years, 40% were male, 45% had cumulated Kellgren-Lawrence (KL)-grade (Right + Left knee) of 2 to 3 and 55% had 4 to 6. Analyzing overall changes, area under the curve was significantly lower compared with resting values for ARGS and C2M after cycling and for ARGS after running. Considering individual time points, peak changes in biomarker levels showed reduction in C2M shortly following cycling (T_20min = -12.3%, 95% confidence interval [CI]: -19.3% to -5.2%). PRO-C2 increased during cycling (T_10min = 14.0%, 95% CI = 4.1% to 23.8%) and running (T_20min = 16.5%, 95% CI = 4.3% to 28.6%). T2CM decreased after cycling (T_50min = -19.9%, 95% CI = -29.2% to -10.6%), running (T_50min = -22.8%, 95% CI = -32.1% to -13.5%), and infusion of adrenaline (peak, T_50min = -9.8%, 95% CI = -20.0% to 0.4%). A latent increase was seen in Coll2-1 240 minutes after running (T_260min = 21.7%, 95% CI = -1.6% to 45.1%).ConclusionExercise had an impact on cartilage markers, but it did not suggest any detrimental effect on cartilage. Changes following adrenaline infusion suggest a sympathomimetic influence on the serological composition of biomarkers.