Search Results (128)

Background/Objectives: Malnutrition is an imbalance of nutrients required for growth, development, and organ function. Its impact on bone development is known, but its effects on cartilage remain unclear. This study aimed to evaluate the femoral cartilage thickness in children with primary malnutrition. Methods: In this cross-sectional observational study, 83 children with primary malnutrition and 62 age- and sex-matched healthy controls were included. Patients with primary malnutrition were classified as mild, moderate and severe. Femoral cartilage thickness measurements of all children were taken by ultrasound from the femoral lateral condyle, femoral medial condyle and intercondylar area for both knees with the patient in a supine position with the knees flexed 90 degrees. Results: The right lateral, right medial, left lateral, and left medial femoral cartilages were significantly thicker in patients with malnutrition compared to those without malnutrition (p = 0.002, 0.004, <0.001, and 0.001, respectively). A significant negative correlation was found between age, weight Z-score, and height Z-score and triceps skinfold thickness. Conclusions: Distal femoral cartilage thickness is significantly greater in children with primary malnutrition. This demonstrates the effect of nutritional factors on cartilage tissue and suggests that children with chronic malnutrition are at risk for both knee joint problems and short stature later in life. Full article

Current osteoarthritis (OA) therapies fail to yield long-term clinical benefits, due in part to the lack of a mechanism for the targeted and confined delivery of therapeutics to OA joints. This study evaluates if M2 macrophages are effective cell vehicles for the targeted and confined delivery of therapeutic genes to OA joints. CT bioluminescence in vivo cell tracing and fluorescent microscopy reveal that intraarticularly injected M2 macrophages were recruited to and retained at inflamed synovia. The feasibility of an M2 macrophage-based adoptive gene transfer strategy for OA was assessed using IL-1Ra as the therapeutic gene in a mouse tibial plateau injury model. Mouse M2 macrophages were transduced with lentiviral vectors expressing IL-1Ra or GFP. The transduced macrophages were intraarticularly injected into injured joints at 7 days post-injury and OA progression was monitored with plasma COMP and histology at 4 weeks. The IL-1Ra-expressing M2 macrophage treatment reduced plasma COMP, increased the area and width of the articular cartilage layer, decreased synovium thickness, and reduced the OARSI OA score without affecting the osteophyte maturity and meniscus scores when compared to the GFP-expressing M2 macrophage-treated or PBS-treated controls. When the treatment was given at 5 weeks post-injury, at which time OA should have developed, the IL-1Ra-M2 macrophage treatment also reduced plasma COMP, had a greater articular cartilage area and width, decreased synovial thickness, and reduced the OARSI OA score without an effect on the meniscus and osteophyte maturity scores at 8 weeks post-injury. In conclusion, the IL-1Ra-M2 macrophage treatment, given before or after OA was developed, delayed OA progression, indicating that the M2 macrophage-based adoptive gene transfer strategy for OA is tenable. Full article

Osteoarthritis (OA) is a leading cause of disability worldwide and is characterized by the gradual degradation of articular cartilage in weight-bearing joints, notably the knees and hips. However, the primary morphological and anatomical determinants of the disease onset and progression remain unclear. This narrative overview examines how variations in cartilage thickness—traditionally viewed as a biomechanical protective feature—can paradoxically compromise metabolic homeostasis during prolonged sedentary behavior. Intriguingly, compelling evidence suggests that despite its superior load-bearing capacity, thicker cartilage faces greater challenges in solute transport, a limitation further exacerbated by the formation of diffusion-resistant boundary layers at the cartilage–fluid interface during immobilization. This phenomenon restricts nutrient influx and impedes waste clearance, leading to the accumulation of catabolic byproducts in deep cartilage zones and accelerated extracellular matrix breakdown, potentially influencing OA pathogenesis. By critically synthesizing current debates on mechanical loading with emerging data on metabolic dysregulation, particularly nutrient diffusion limitations, this analysis underscores the urgent need for targeted investigation of synovial–cartilage interface dynamics and chondrocyte metabolism under low-motion conditions. This study further advocates for strategic research focusing on often-overlooked, silent metabolic imbalances among sedentary populations and recommends early-intervention strategies, such as periodic joint mobilization, ergonomic adaptations, and public-health campaigns, to reduce prolonged sitting, preserve joint function, and guide more effective prevention and management approaches for non-traumatic OA in contemporary contexts. Full article

Background/Objectives: This review analyzes the effects of invasive and non-invasive methods of knee joint unloading on knee loading, employing a biomechanical model to evaluate their impact. Methods: PubMed, Web of Science, Cochrane, and Scopus were searched up to 15 May 2024 to identify eligible clinical studies evaluating Joint Space Width, Cartilage Thickness, the Western Ontario and McMaster Universities Osteoarthritis Index, the Knee Injury and Osteoarthritis Outcome Score system, Gait velocity, Peak Knee Adduction Moment, time to return to sports and to work, ground reaction force, and the visual analogue scale pain score. A second search was conducted to select a biomechanical model that could be parametrized, including the modifications that each treatment would impose on the knee joint and was capable of estimate joint loading to compare the effectiveness of each method. Results: Analyzing 28 studies (1652 participants), including 16 randomized clinical trials, revealed significant improvements mainly when performing knee joint distraction surgery, increasing Joint Space Width even after removal, and high tibial osteotomy, which realigns the knee but does not reduce loading. Implantable shock absorbers are also an attractive option as they partially unload the knee but require further investigation. Non-invasive methods improve biomechanical indicators of knee joint loading; however, they lack quantitative analysis of cartilage volume or Joint Space Width. Conclusions: Current evidence indicates a clear advantage in knee joint unloading methods, emphasizing the importance of adapted therapy. However, more extensive research, particularly using non-invasive approaches, is required to further understand the underlying knee joint loading mechanisms and advance the state of the art. Full article

Unilateral vocal fold paralysis (UVFP) can lead to significant dysphonia. Medialization thyroplasty type 1 (TT1) is a common surgical intervention aiming at improving vocal quality by optimally positioning the paralyzed fold to generate the necessary vibrations for phonation. Implants are generally placed through the thyroid cartilage in a sedated patient and positioned either underneath the level of the vocal folds (infraglottal medialization or IM) or at the level of the vocal folds (glottal medialization or GM). Using high-speed three-dimensional digital image correlation (3D-DIC) in an ex vivo canine hemilarynx model, this study explores the impact of implant location, specifically IM versus GM on the pre-phonatory and dynamic vertical thickness, glottal divergence, flow rate (Q), and cepstral peak prominence (CPP) under varying adduction and subglottal pressure conditions. IM consistently increased glottal divergence and dynamic vertical thickness, particularly in under-adducted states (AL1), despite producing lower static thickness than GM. CPP remained unaffected by the implant condition, but Q decreased significantly with IM under AL1, indicating enhanced glottal resistance and closure. These findings suggest that IM may offer superior functional outcomes by restoring divergent glottal shaping and improving vibratory efficiency. This study also introduces a validated method for dynamically quantifying vocal fold thickness and emphasizes the importance of implant depth in medialization thyroplasty strategies. Full article

Background/Objectives: In the original canine groove model of osteoarthritis (OA), superficial scratches to the cartilage lead to slow progressive cartilage damage, with inflammation mimicking key aspects of human disease. The present study assesses a modified canine groove model with full-thickness cartilage grooves, gouged with a 3-mm biopsy punch, in the femoral condyles. This modified model enables the study of cartilage repair techniques, such as scaffold implantation. Methods: Cartilage defects were induced in the right knee of five mongrel dogs (four females, one male; 17 ± 4 months; 25.9 ± 2.0 kg) using the modified groove model, creating two full-thickness cartilage grooves on the femoral condyles. Data of a previously studied cohort of nine dogs (nine females; 18 ± 6 months; 17.6 ± 0.7 kg) with OA induced according to the original groove model served as the canine OA standard. Both groups were monitored up to 45 weeks post-surgery. Pain/function was assessed by force plate analysis, and cartilage integrity, chondrocyte activity, and synovial inflammation were evaluated on the surgically untouched tibial plateaus by macroscopic, histologic, and biochemical analyses. Results: Force plate analysis showed no significant changes in either group. Both models exhibited OA features. Experimental knees had more macroscopic and histologic damage, reduced proteoglycan content, and impaired retention of proteoglycans than controls. The modified groove model had less severe cartilage damage and synovial inflammation (p = 0.026, p = 0.017), with no other significant differences. Conclusions: The modified groove model induces OA at a slow pace, mirroring post-traumatic OA development in humans. It represents a mild OA model, comparable to the original groove model, and may be useful for evaluating cartilage repair strategies, such as scaffold implantation. Full article

Background/Objectives: This scoping review explores the relationship between ultra-processed food (UPF), bone health, and joint diseases, focusing on its potential impact on bone mineral density (BMD), osteoporosis, osteoarthritis, and inflammatory arthritis, including rheumatoid arthritis (RA), gout, and spondyloarthritis. Methods: A search strategy was developed using key terms such as “ultra-processed food” and related terms like “fast food,” alongside various definitions of bone health impairment, chronic degenerative joint diseases, and inflammatory arthritis. Results: A total of 19 studies were included: 12 on bone health, 3 on osteoarthritis, and 4 on inflammatory arthritis. Preclinical studies showed that UPF consumption negatively affects bone structure and strength. In studies on children and adults, four investigations (2013–2017) found no association between fast food intake and BMD. However, more recent large-scale cross-sectional studies linked higher UPF consumption to lower BMD, increased osteoporosis risk, and greater prevalence of osteopenia, particularly in postmenopausal women. UPF intake was associated with knee osteoarthritis risk, with evidence suggesting an interaction with cartilage thickness, though no association was found for hip osteoarthritis. In inflammatory arthritis, UK Biobank data indicated a higher risk of RA and gout in UPF consumers, while a Brazilian study reported worse metabolic profiles in RA patients. No significant differences in UPF intake were found in spondyloarthritis. Conclusions: This review highlights relevant considerations about the deleterious role of UPF on bone health and joint diseases, providing additional evidence to suggest healthier dietary patterns to patients and to the general population. Full article

Aim: This study aims to assess the suitability of the Göttingen Mini-pig (G-MP) as a large animal model for preclinical research on articular cartilage treatment procedures. Additionally, this study compares the G-MP to the domestic pig (DP) regarding surgical anatomy, postoperative care, and the challenges associated with the follow-up period. Materials and methods: Six G-MPs and four DPs underwent a two-stage surgical procedure: first, cartilage was harvested using a superolateral approach, followed by cartilage implantation via a medial parapatellar tendon approach. Results: The superolateral approach exposed 11% (SD ± 5) of the trochlea in G-MPs and 20% in DPs. The medial parapatellar tendon approach exposed 63% (SD ± 4) of the trochlear surface and 34% (SD ± 13) of the medial femoral condyle in G-MPs, allowing for the creation of four 6 mm trochlear lesions and one medial condyle lesion in four out of six G-MPs and all DPs. Cartilage thickness was less than 1 mm in G-MPs, compared to over 2 mm in DPs. Weight gain was +4 kg/week in DPs and +0.2 kg/week in G-MPs. Conclusion: Overall, the G-MP proves to be a viable model for cartilage research, offering sufficient joint access via the dual approach, which allows for 4–5 lesions of 6 mm each. However, the thinner cartilage in G-MPs should be taken into account. Full article

The mandibular condyle cartilage serves as a principal zone for mandible growth, and any dysplasia could contribute to skeletal mandibular hypoplasia (SMH). The aim of the study was to further explore how TFRC signaling regulates condylar cartilage development. In this study, TFRC, SLC39A14, chondrogenic markers and ferroptosis-related signals were detected in the condylar cartilage of postnatal mice and Tfrc cartilage conditional knockout (Tfrc-cKO) mice at different time points through immunofluorescence, immunohistochemical staining and qPCR assays. The overexpression and knockdown of TFRC in the ATDC5 cell line were used to investigate its role in a specific biological process. Co-immunoprecipitation was used to verify protein–protein interaction in vitro. Ferroptosis inhibitor Fer1, Ac-Met-OH and DFP were used for an in vitro rescue assay. The temporomandibular joint injection of DFP was used to rescue the cartilage phenotype in vivo. Our results verified that TFRC was crucial for condylar cartilage development. TFRC ablation led to condylar cartilage thickness and condyle length alterations and induced the ferroptosis of chondrocyte by upregulating SLC39A14. Mitochondrial p53 translocation was involved in the TFRC–SLC39A14 switch by SLC39A14 ubiquitination degradation. Fer1, Ac-Met-OH and DFP inhibited ferroptosis and restored chondrogenic differentiation in vivo. The temporomandibular joint injection of DFP could rescue the cartilage phenotype. In summary, this study reveals that TFRC influences postnatal condylar cartilage development through mitochondrial p53 translocation-mediated ferroptosis, which provides insights into the etiology, pathogenesis, and therapy of mandibular hypoplasia and even systemic articular cartilage dysplasia. Full article

(1) Background: Osteoarthritis is a degenerative disease of the whole joint marked by cartilage–bone interface (CBI) remodeling, but methods to monitor subtle changes in mineralization are lacking. We optimized a non-destructive ultrasound imaging method to monitor incremental shifts in mineralization, using brief decalcification as a mimetic of CBI remodeling. (2) Methods: We used a 35-MHz transducer to scan 3 mm diameter bovine osteochondral explants wrapped with parafilm to produce surface-directed decalcification and dedicated 3D-printed holders to maintain sample orientation. Customized MATLAB codes and a matched pair design were used for quantitative hypothesis testing. (3) Results: Optimal scan precision was obtained when the High-Frequency Ultrasound (HFUS) focal distance was trained at the CBI. HFUS cartilage thickness increased by 53 ± 21 µm or 97 ± 28 µm after three or seven hours of ethylene diamine tetra-acetic acid (EDTA) (but not PBS), respectively, and was highly correlated with histological cartilage thickness (R = 0.98). The en face CBI backscatter pattern was irregular and shifted after the EDTA-displacement of the mineral front. Collective data suggested that the −10 dB echogenic CBI signal originated from the mineral front and varied topographically with undulating mineral thickness. (4) Conclusions: This imaging approach could be used to monitor tidemark remodeling in live explant cultures, toward identifying new treatments that inhibit tidemark advancement and slow osteoarthritis progression. Full article

Osteoarthritis (OA), caused by the long-term use of joints, is a representative degenerative disease in the elderly. However, recently, the age of onset has been decreasing owing to excessive activities among young people in their 20s and 30s. Gynostemma pentaphyllum (Thunb.) Makino (GP), a perennial herb of the Cucurbitaceae family, has been used since the Ming dynasty as a medicinal material to treat various ailments, such as rheumatism, liver disease, and diabetes. In this study, we investigated the anti-arthritic effects of heat-processed Gynostemma pentaphyllum extract (Actiponin (AP)) and its derivatives, damulin A (DA) and damulin B (DB), using in vitro (primary rat chondrocytes and SW1353 cells) and in vivo (destabilization of the medial meniscus (DMM)-induced OA model) systems. Histological analysis results from the in vivo study showed that the group that underwent DMM surgery induced degeneration by the loss of proteoglycan and the destruction of cartilage (OARSI score 14 ± 0.57), whereas the group that received AP daily for 8 weeks maintained an intact condition (OARSI score 5 ± 0.28 at 200 mg/kg, p < 0.001). In addition, cartilage thickness and chondrocytes were reduced in the DMM group, but were restored in the AP-administered group. Furthermore, the von Frey analysis results showed that the pain threshold of the DMM group was considerably low (54.5 g at 8 weeks), whereas that of the AP group was dose-dependently increased (65.5, 69.5, 70.3, and 71.8 at 8 weeks for 30, 50, 100, and 200 mg/kg, respectively). In vitro studies showed that AP, DA, and DB reduced the expression of interleukin-1β alone-induced nitrite; inducible nitric oxide synthase; cyclooxygenase-2; matrix metallopeptidase 1/3/13; and a disintegrin and metalloproteinase with thrombospondin motifs 4/5. They also restored the expression of collagen type II and aggrecan, which are components of the extracellular matrix. The anti-arthritic effects of AP, DA, and DB were confirmed to be mediated by the mitogen-activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cell signaling pathways. Collectively, these results suggest that AP is a potential therapeutic agent for mitigating OA progression and chondroprotection. Full article

Extracellular vesicles (EVs), particularly exosomes (EXOs) of various skeletal and stem cells, were shown to delay osteoarthritis (OA) progression, and apoptotic bodies (ABs), another EV subtype, of osteoclasts showed osteoanabolic actions and were involved in the osteoclastic-regulation of local bone formation. Moreover, this study demonstrates that microvesicles (MVs) released by osteoclasts displayed potent pro-chondrogenic, pro-osteogenic, and anti-inflammatory activities. These activities were unique to osteoclastic MVs and were not shared by osteoclastic ABs and EXOs or MVs of other cell types. Because chronic synovial inflammation, progressive articular cartilage erosion, abnormal subchondral bone remodeling, and inability to regenerate articular cartilage are key etiologies of OA, we postulate that the foregoing activities of osteoclastic MVs could simultaneously target multiple etiologies of OA and could thereby be an effective therapy for OA. Accordingly, this study sought to assess the feasibility of an osteoclastic MV-based strategy for OA with a mouse tibial plateau injury model of OA. Briefly, tibial plateau injuries were created on the right knees of adult C57BL/6J mice, MVs were intraarticularly injected into the injured joints biweekly, and the OA progression was monitored histologically at five weeks post-injury. The MV treatment reduced the OA-induced losses of articular cartilage area and thickness, decreased irregularity in the articular cartilage surface, reduced loss of gliding/intermediate zone of articular cartilage, reduced osteophyte formation, suppressed synovial inflammation, and decreased the OARSI OA score. In summary, treatment with osteoclastic MVs delayed or reversed OA progression. Thus, this study supports the feasibility of an osteoclastic MV-based therapy for OA. Full article

The shortage of tissues and damaged organs led to the development of tissue engineering. Biological scaffolds, created from the extracellular matrix (ECM) of organs and tissues, have emerged as a promising solution for transplants. The ECM of decellularized auricular cartilage is a potential tool for producing ideal scaffolds for the recellularization and implantation of new tissue in damaged areas. In order to be classified as an ideal scaffold, it must be acellular, preserving its proteins and physical characteristics necessary for cell adhesion. This study aimed to develop a decellularization protocol for pig ear cartilage and evaluate the integrity of the ECM. Four tests were performed using different methods and protocols, with four pig ears from which the skin and subcutaneous tissue were removed, leaving only the cartilage. The most efficient protocol was the combination of trypsin with a sodium hydroxide solution (0.2 N) and SDS (1%) without altering the ECM conformation or the collagen architecture. In conclusion, it was observed that auricular cartilage is difficult to decellularize, influenced by material size, exposure time, and the composition of the solution. Freezing and thawing did not affect the procedure. The sample thickness significantly impacted the decellularization time. Full article

Background: Osteoarthritis is caused by damage to the articular cartilage due to bone-on-bone collisions and friction. The length, width, and thickness of the ligaments are expected to change in order to regulate excessive bone-to-bone movement. We aimed to clarify the relationship between ligament morphology and joint surface degeneration in the ankle joints using macroscopic observations and measurements. Methods: The participants were 50 feet of 45 Japanese cadavers. The lengths, widths, and thicknesses of the tibionavicular, tibiospring, tibiocalcaneal, posterior tibiotalar, anterior tibiotalar, and calcaneofibular ligaments (CFLs) were measured. The degeneration of the talonavicular joint surface was investigated macroscopically and classified into two groups: the Degeneration (+) group and Degeneration (−) group. Unpaired t-tests were performed for each measurement. Logistic regression analysis was performed on the significantly different items to obtain cutoff values, sensitivity, and specificity. Results: Only the width of the CFL differed significantly between the Degeneration (+) (20 feet) and Degeneration (−) groups (p < 0.001). In the logistic regression analysis, the width of the CFL had an R2 of 0.262, sensitivity of 75.0%, and specificity of 83.3%, with a cutoff value of 8.7 mm. Conclusions: A wide CFL indicates a high likelihood of talonavicular articular surface degeneration. Full article

Background/Objectives: Cartilage injuries and osteoarthritis are prevalent public health problems, due to their disabling nature and economic impact. Mesenchymal stromal cells (MSCs) isolated from different tissues have the immunomodulatory capacity to regulate local joint environment. This translational study aims to compare cartilage restoration from MSCs from the synovial membrane (SM) and dental pulp (DP) by a tissue-engineered construct with Good Manufacturing Practices. Methods: A controlled experimental study was conducted on fourteen miniature pigs, using scaffold-free Tissue Engineering Constructs (TECs) from DP and SM MSCs, with a 6-month follow-up. Total thickness cartilage defects were created in both hind knees; one side was left untreated and the other received a TEC from either DP (n = 7) or SM (n = 7). An MRI assessed the morphology using the MOCART scoring system, T2 mapping evaluated water, and collagen fiber composition, and histological analysis was performed using the ICRS-2 score. Results: The untreated group had a mean MOCART value of 46.2 ± 13.4, while the SM-treated group was 65.7 ± 15.5 (p < 0.05) and the DP-treated group was 59.0 ± 7.9 (n.s.). The T2 mapping indicated a mean value of T2 of 54.9 ± 1.9 for native cartilage, with the untreated group at 50.9 ± 2.4 (p < 0.05). No difference was found between the T2 value of native cartilage and the treated groups. The ICRS-2 mean values were 42.1 ± 14.8 for the untreated group, 64.3 ± 19.0 for SM (p < 0.05), and 54.3 ± 12.2 for DP (n.s.). Conclusion: MRI and histological analysis indicated that TEC treatment led to superior cartilage coverage and quality compared to the defect group. TECs from SM demonstrated better results than the defect group in the histological assessment. Full article