CARTILAGE最新文献

Objective: The superficial zone cells in articular cartilage (SFZCs) have been identified as stem/progenitor chondrocytes and promoted cell self-renewal in the osteoarthritis (OA). Several studies emphasized the involvement of senescence and autophagy in OA. Interleukin-1β (IL-1β) is one of the main inflammatory mediators of OA, and whether it induces senescence and autophagy in SFZCs remains unclear. The present study aimed to investigate autophagy flux, mitochondrial function, and intracellular reactive oxygen species (ROS) that resulted in senescence in SFZCs induced by IL-1β.

Methods: Using western blotting, reverse transcription-quantitative PCR, immunofluorescence, intracellular ROS detection, mitochondrial staining, and determination of mitochondrial membrane potential, we tested senescence and autophagy markers in SFZCs induced by IL-1β in vitro. The consequences of mitochondrial function and ROS were also studied with IL-1β-induced senescence.

Results: IL-1β treatment decreased SFZC proliferation, induced SFZC senescence, and reduced SFZCs' chondrogenic differentiation capacity. Moreover, IL-1β impaired autophagy flux, and the autophagy activator, rapamycin, attenuated the senescence of SFZCs. IL-1β-induced autophagy defect resulted in mitochondrial dysfunction and overproduction of ROS, and autophagy activation notably protected against mitochondrial dysfunction and reduced the levels of ROS. Moreover, antioxidant N-acetylcysteine reversed the senescence of IL-1β in SFZCs.

Conclusion: IL-1β promotes autophagy impairment and subsequently results in dysfunctional mitochondria and overproduction of ROS, which finally causes SFZC senescence.

Objective: Activation of sympathetic tone is important for cartilage degradation in osteoarthritis (OA). Recent studies reported that sympathetic signals can affect the mitochondrial function of target cells. It is unknown whether this effect exits in chondrocytes and affects chondrocyte catabolism. The contribution of mitochondrial dynamics in the activation of α2-adrenergic signal-mediated chondrocyte catabolism was investigated in this study.

Design: Primary chondrocytes were stimulated with norepinephrine (NE) alone, or pretreated with an α2-adrenergic receptor (Adra2) antagonist (yohimbine) and followed by stimulation with NE. Changes in chondrocyte metabolism and their mitochondrial dynamics were investigated.

Results: We demonstrated that NE stimulation induced increased gene and protein expressions of matrix metalloproteinase-3 and decreased level of aggrecan by chondrocytes. This was accompanied by upregulated mitochondriogenesis and the number of mitochondria, when compared with the vehicle-treated controls. Mitochondrial fusion and fission, and mitophagy also increased significantly in response to NE stimulation. Inhibition of Adra2 attenuated chondrocyte catabolism and mitochondrial dynamics induced by NE.

Conclusions: The present findings indicate that upregulation of mitochondrial dynamics through mitochondriogenesis, fusion, fission, and mitophagy is responsible for activation of α2-adrenergic signal-mediated chondrocyte catabolism. The hypothesis that "α2-adrenergic signal activation promotes cartilage degeneration in temporomandibular joint osteoarthritis (TMJ-OA) by upregulating mitochondrial dynamics in chondrocytes" is validated. This represents a new regulatory mechanism in the chondrocytes of TMJ-OA that inhibits abnormal activation of mitochondrial fusion and fission is a potential regulator for improving mitochondrial function and inhibiting chondrocyte injury and contrives a potentially innovative therapeutic direction for the prevention of TMJ-OA.

Objective: Obesity and associated low-level local systemic inflammation have been linked to an increased rate of developing knee osteoarthritis (OA). Aerobic exercise has been shown to protect the knee from obesity-induced joint damage. The aims of this study were to determine (1) if resistance training provides beneficial metabolic effects similar to those previously observed with aerobic training in rats consuming a high-fat/high-sucrose (HFS) diet and (2) if these metabolic effects mitigate knee OA in a diet-induced obesity model in rats.

Design: Twelve-week-old Sprague-Dawley rats were randomized into 4 groups: (1) a group fed an HFS diet subjected to aerobic exercise (HFS+Aer), (2) a group fed an HFS diet subjected to resistance exercise (HFS+Res), (3) a group fed an HFS diet with no exercise (HFS+Sed), and (4) a chow-fed sedentary control group (Chow+Sed). HFS+Sed animals were heavier and had greater body fat, higher levels of triglycerides and total cholesterol, and more joint damage than Chow+Sed animals.

Results: The HFS+Res group had higher body mass and body fat than Chow+Sed animals and higher OA scores than animals from the HFS+Aer group. Severe bone lesions were observed in the HFS+Sed and Chow+Sed animals at age 24 weeks, but not in the HFS+Res and HFS+Aer group animals.

Conclosion: In summary, aerobic training provided better protection against knee joint OA than resistance training in this rat model of HFS-diet-induced obesity. Exposing rats to exercise, either aerobic or resistance training, had a protective effect against the severe bone lesions observed in the nonexercised rats.

Objective: Distraction treatment for severe osteoarthritis below the age of 65 successfully postpones arthroplasty. Most patients have been treated with a general external fixator or a device specifically intended for knee distraction. This study compares clinical efficacy of both devices in retrospect and their mechanical characteristics.

Design: Clinical efficacy 2 years posttreatment was compared using retrospective data from patients with severe knee osteoarthritis treated with knee distraction; 63 with the Dynamic Monotube (Stryker GmbH, Switzerland) and 65 with the KneeReviver (ArthroSave BV, the Netherlands). Changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, stiffness, and function, general well-being (SF-36), cartilage thickness by radiographic joint space widening, and adverse events during treatment were assessed. Axial stiffness of clinically feasible configurations was assessed by bench testing for the Dynamic Monotube triax system and the KneeReviver.

Results: No differences were observed in clinical efficacy, nor in mechanical characteristics and adverse events between the two devices. Although with large variation, both showed a clinically relevant improvement. In mechanical testing, contact between articular surfaces was observed for both devices at physiological loading. Stiffness of applied configurations strongly varied and primarily depended on bone pin length.

Conclusions: Patients treated with a general intended-use device or a distraction-specific device both experienced clinical and structural efficacy although with significant variation between patients. The latter may be the result of varying mechanical characteristics resulting from differences in clinical configurations of the devices and actual loading. The exact role of full/partial mechanical unloading of the joint during distraction treatment remains unclear.

Objective: Mechanical loading is an essential factor for the maintenance of joint inflammatory homeostasis and the sensitive catabolic-anabolic signaling cascade involved in maintaining cartilage tissue health. However, abnormal mechanical loading of the joint structural tissues can propagate joint metabolic dysfunction in the form of low-grade inflammation. To date, few studies have attempted to delineate the early cascade responsible for the initiation and perpetuation of stress-mediated inflammation and cartilage breakdown in human joints.

Design: Fifteen healthy human male participants performed a walking paradigm on a cross-tilting treadmill platform. Blood samples were collected before exercise, after 30 minutes of flat walking, after 30 minutes of tilted walking, and after an hour of rest. Serum concentrations of the following biomarkers were measured: interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor alpha (TNF)-α, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, MMP-13, transforming growth factor beta (TGF)-β, tissue inhibitor of matrix metalloproteinase 1 (TIMP)-1, and cartilage oligomeric protein (COMP).

Results: Luminex Multiplex analysis of serum showed increased concentrations of COMP, IL-1β, TNF-α, IL-10, and TGF-β from samples collected after flat and cross-tilted treadmill walking compared to baseline. Serum concentrations of MMP-1 and MMP-13 also increased, but primarily in samples collected after tilted walking. Pearson's correlation analysis showed positive correlations between the expression of COMP, TNF-α, IL-10, and MMP-13 at each study timepoint.

Conclusion: Stress-mediated increases in serum COMP during exercise are associated with acute changes in pro and anti-inflammatory molecular activity and subsequent changes in molecules linked to joint tissue remodeling and repair.

Objective: Marrow stimulation is used to address knee cartilage defects. In this study, we used the fragility index (FI), reverse fragility index (rFI), and fragility quotient (FQ) to evaluate statistical fragility of outcomes reported in randomized controlled trials (RCTs) evaluating marrow stimulation.

Design: PubMed, Embase, and MEDLINE were queried for recent RCTs (January 1, 2010-September 5, 2023) assessing marrow stimulation for cartilage defects of the knee. The FI and rFI were calculated as the number of outcome event reversals required to alter statistical significance for significant and nonsignificant outcomes, respectively. The FQ was determined by dividing the FI by the study sample size.

Results: Across 155 total outcomes from 21 RCTs, the median FI was 3 (interquartile range [IQR], 2-5), with an associated median FQ of 0.067 (IQR, 0.033-0.010). Thirty-two outcomes were statistically significant, with a median FI of 2 (IQR, 1-3.25) and FQ of 0.050 (IQR, 0.025-0.069). Ten of the 32 (31.3%) outcomes reported as statistically significant had an FI of 1. In total, 123 outcomes were nonsignificant, with a median rFI of 3 (IQR, 2-5). Studies assessing stem cell augments were the most fragile, with a median FI of 2. In 55.5% of outcomes, the number of patients lost to follow-up was greater than or equal to the FI.

Conclusion: Statistical findings in RCTs evaluating marrow stimulation for cartilage defects of the knee are statistically fragile. We recommend combined reporting of P-values with FI and FQ metrics to aid in the interpretation of clinical findings in comparative trials assessing cartilage restoration.

Objective: After traumatic knee injuries, chondral fragments can avulse off bone with the progeny fragment becoming a loose body. The loose fragment may be larger than expected when trying to surgically repair the fragment back to its original site. The purpose of this study was to determine whether a loose chondral fragment from the lateral femur condyle would increase in size and weight after soaking in normal saline (NS) for 14 days.

Design: Twelve 6-mm OAT (osteoarticular transfer) plugs were harvested from 6 cadaver knees on the lateral femoral condyle to simulate a chondral fragment. The chondral fragments were then placed inside an airtight specimen container with NS (0.9% sodium chloride) and were measured over 14 days.

Results: After 14 days, the chondral fragments showed no increase in diameter as they measured an average of 5.567 ± 0.448 mm on Day 1 and 5.702 ± 0.253 mm on Day 14 (P = 0.183). The chondral fragments showed an increase in mass from an average of 0.058 ± 0.012 g on Day 1 to 0.073 ± 0.012 g on Day 14 (P < 0.001) and an increase in thickness from an average of 2.038 ± 0.346 mm on Day 1 to 2.229 ± 0.297 mm on Day 14 (P = 0.033).

Conclusions: Chondral fragments in NS increase in mass and thickness over time, but do not change in diameter. When surgeons are evaluating loose chondral fragments for fixation, they should consider that these fragments may appear thicker than the recipient location.

Objective: Ex vivo nanoindentation measurement has reported that elastic modulus decreases as cartilage degenerates, but no method has been established to macroscopically evaluate mechanical properties in vivo. The objective of this study was to evaluate the elastic modulus of knee joint cartilage based on macroscopic methods and to compare it with gross and histological findings of degeneration.

Design: Osteochondral sections were taken from 50 knees with osteoarthritis (average age, 75 years) undergoing total knee arthroplasty. The elastic modulus of the cartilage was measured with a specialized elasticity tester. Gross findings were recorded as International Cartilage Repair Society (ICRS) grade. Histological findings were graded as Mankin score and microscopic cartilage thickness measurement.

Results: In ICRS grades 0 to 2 knees with normal to moderate cartilage abnormalities, the elastic modulus of cartilage decreased significantly as cartilage degeneration progressed. The elastic modulus of cartilage was 12.2 ± 3.8 N/mm for ICRS grade 0, 6.3 ± 2.6 N/mm for ICRS grade 1, and 3.8 ± 2.4 N/mm for ICRS grade 2. Similarly, elastic modulus was correlated with Mankin score (r = -0.51, P < 0.001). Multiple regression analyses showed that increased Mankin score is the most relevant factor associated with decreased elastic modulus of the cartilage (t-value, -4.53; P < 0.001), followed by increased histological thickness of the cartilage (t-value, -3.15; P = 0.002).

Conclusions: Mechanical properties of damaged knee cartilage assessed with new macroscopic methods are strongly correlated with histological findings. The method has potential to become a nondestructive diagnostic modality for early cartilage damage in the clinical setting.

Objective: The various functionalities of collagen peptides have generated a large interest in utilizing the bioactive peptides as a nutritional therapy to ameliorate various physiological degenerative conditions. Collagen peptides are observed to reduce the pain and aligned difficulties with respect to osteoarthritis. Here we report the enhanced ameliorating property of novel high-functional "Wellnex" Type J collagen peptides following a double-blind randomized active and placebo-controlled 5-arm clinical trial (n = 100) by using it as a nutritional supplement in subjects with knee joint osteoarthritis in comparison with conventional bovine collagen peptides. The efficacy, safety, and tolerability were also studied.

Design: Dosages of 2.5, 5.0, and 10.0 g of high-functional Type J bovine collagen peptides, 10.0 g of conventional collagen peptides, and 10.0 g of placebo were given to the 5 groups for a period of 90 days. The Western Ontario McMaster Universities Arthritis Index (WOMAC) score, Pain Scale, Quality of Life (QoL), Physician's Impression of change Score (PICS), serum C-terminal cross-linked telopeptide of type II collagen (CTX-II) levels and Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) parameters were monitored.

Results: Type J 2.5 g showed significant improvement in WOMAC, QoL, CTX, and MOAKS and observed to be equivalent to conventional collagen peptide 10-g supplementation in terms of efficacy.

Conclusion: The two significant outcomes of the study were that Type J 10.0 g, Type J 5.0 g, Type J 2.5 g and conventional collagen peptides 10.0 g supplementation were observed to be beneficial nutraceutical therapies for knee joint osteoarthritis, and Type J 2.5 g supplementation was equivalent to conventional collagen peptides 10.0-g supplementation in terms of efficacy.

Objective: To analyze the prognostic factors for clinical outcomes and cartilage regeneration after the implantation of allogeneic human umbilical cord blood mesenchymal stem cell (hUCB-MSC) for treating large-sized cartilage defects with osteoarthritis.

Design: This study is a case-series with multiple subgroup analyses that divides the included patients into multiple subgroups based on various factors. Overall, 47 patients who underwent hUCB-MSC implantation were included. The patient-reported outcomes, magnetic resonance imaging (MRI), and second-look arthroscopy were used to assess the outcomes.

Results: Combined realignment surgery significantly correlated with clinical outcomes, particularly pain. No other factors significantly influenced the clinical outcomes in short-term period. Subgroups with large defect sizes or meniscal insufficiency showed significantly poor MRI and arthroscopy outcomes (MRI, P = 0.001, P = 0.001; arthroscopy, P = 0.032, P = 0.042). The logistic regression showed that patients with a 1 cm² larger defect size were 1.91 times less likely to achieve favorable MRI outcomes (P = 0.017; odds ratio [OR], 1.91). Cut-off value to predict the poor outcome was >5.7 cm² (area under the curve, 0.756). A cartilage defect size >5.7 cm² was the major poor prognostic factor for cartilage regeneration on MRI (P = 0.010; OR, 17.46). If the postoperative alignment shifted by 1° opposite to the cartilage defect, it was 1.4 times more likely to achieve favorable MRI outcomes (P = 0.028; OR, 1.4).

Conclusion: Combining realignment surgery showed a better prognosis for pain improvement. Cartilage defect size, meniscal function, and postoperative alignment are significant prognostic factors for cartilage regeneration. A cartilage defect size >5.7 cm² was significantly related to poor cartilage regeneration.