CARTILAGE最新文献

Objective: This study aimed to decipher the temporal and spatial signaling code for clinical cartilage and bone regeneration. We investigated the effects of continuous equal dosages of a single, dual, or triplicate growth factor combination of bone morphogenetic protein (BMP)-2, transforming growth factor (TGF)-β3, and/or BMP-7 on muscle tissue over a culturing period. The hypothesis was that specific growth factor combinations at specific time points direct tissue transformation toward endochondral bone or cartilage formation.

Design: The harvested muscle tissues from F-344 adult male rats were cultured in 96-well plates maintained in a specific medium and cultured at specific conditions. And the multidimensional and multi-time point analyses were performed at both the genetic and protein levels.

Results: The results insinuate that the application of growth factor stimulates a chaotic tissue response that does not follow a chronological signaling cascade. Both osteogenic and chondrogenic genes showed upregulation after induction, a similar result was also observed in the semiquantitative analysis after immunohistochemical staining against different antigens.

Conclusions: The study showed that multiple TGF-β superfamily proteins applied to tissue stimulate developmental tissue processes that do not follow current tissue formation rules. The findings contribute to the understanding of the chronological order of signals and expression patterns needed to achieve chondrogenesis, articular chondrogenesis, or osteogenesis, which is crucial for the development of treatments that can regrow bone and articular cartilage clinically.

Objective: Ultra-short TE (UTE) sequences on MRI are a technique that improves the visualization of tissues with short T2 relaxation time, such as deep cartilage layers. In addition, T2* relaxation time calculated from the UTE has the potential to evaluate water molecules bound to the cartilage matrix. This study was performed to determine if there is an association between UTE-T2* relaxation time by cartilage layer and histological degeneration in knee osteoarthritis (OA).

Design: Seven knees that had undergone total knee arthroplasty (TKA) were included in the study, and the lateral tibial cartilage, which had the least degeneration of the resected bones, was used as the sample. The T2* relaxation time of 4 patients with no abnormal findings on MRI was the reference relaxation time. Histological degeneration of TKA samples was assessed by the Mankin score and graded as the early OA group (≤3 points) and the advanced OA group (≥4 points). The association between T2* relaxation time and Mankin grade in each cartilage layer was compared. The effect of angiogenesis to the tidemark on T2* relaxation time was also compared.

Results: T2* relaxation time of the cartilage layer was significantly longer in early OA than that in the control group. In the deep cartilage layer, the mean T2* relaxation time for angiogenesis (-) was 15.7 ms, whereas it was significantly shorter for angiogenesis (+) at 8.2 ms.

Conclusions: The UTE-T2* relaxation time was associated with histological cartilage degeneration, suggesting a potential application in monitoring early cartilage degeneration.

Objective: The medial meniscus extrusion (MME) is associated with increased stress on the knee joint, which leads to cartilage degeneration. To evaluate the etiology of knee osteoarthritis, it is extremely important to create animal models of the disease that more closely resemble actual clinical conditions in terms of symptomatology, molecular biology, and histology. This study aimed to create a clinically relevant model of MME in rats.

Design: Behavioral, molecular biological, and histological changes in the newly developed rat MME model were compared with those in sham and medial meniscus transection and medial collateral ligament transection (MMT) models to examine the characteristics of this model.

Results: In the MME rat model, behavioral evaluation shows abnormalities in gait compared with the other 2 groups, and molecular biological evaluation of the infrapatellar synovia of rats shows that gene expression of inflammatory cytokines, matrix-degrading enzymes, and pain-related nerve growth factor was increased compared with the sham group. Furthermore, histological evaluation reveals that cartilage degeneration was the most severe in the MME group.

Conclusions: The newly developed MME model reproduced the characteristic pathology of MME in clinical practice, such as severe pain, inflammation, and rapid progression of osteoarthritis. The MME model, which might more closely mimic human knee osteoarthritis (OA), could be a useful model for elucidating the pathophysiology and considering therapeutic management for knee OA.

Objective: The main objective of this study is to assess the safety and clinical efficacy of a cell-free bilayer scaffold (MaioRegen Chondro+ by Fin-Ceramica) in patients affected by chondral knee lesions of different origin and localization.

Design: Thirty-one patients with focal chondral lesions of the knee were arthroscopically treated with MaioRegen Chondro+. All patients were prospectively evaluated for a minimum of 2 years using the International Knee Documentation Committee (IKDC) Questionnaire and the Tegner Activity Scale. Cartilage repair was assessed based on the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score at 12 months. Follow-up at 36 months was available for 25 out of 31 patients.

Results: From baseline to 6-, 12-, and 24-month follow-up, IKDC score significantly improved by 19.5 ± 7.27 (95% confidence interval [CI]: 16.9-22.2, P < 0.001), 30.8 ± 7.63 (95% CI: 28.0-33.6, P < 0.001), and 36.2 ± 8.00 points (95% CI: 33.3-39.2, P < 0.001), respectively. Tegner scores documented a substantial clinical improvement as early as 12 months after surgery (change of -0.6 ± 0.62; 95% CI: -0.8 to -0.4, P < 0.001), reaching the preinjury values. There was a statistically significant increase in the MOCART scores (P < 0.001). Comparable results were observed regardless of preintervention demographic characteristics, lesion site or etiology, or the number of treated sites. Notably, the significant clinical benefit was maintained in a subset of patients who reached 3-year follow-up. No adverse events were reported in the entire analyzed population.

Conclusion: MaioRegen Chondro+ is a safe and effective device for the treatment of knee chondral lesions, enabling a significant clinical improvement for at least 2 years.

Objective: Osteoarthritis (OA) is a common degenerative joint disease. The occurrence of OA slowly destroys the soft tissue structure of the patient's joint. Severe cases could lead to disability. Current studies had shown that inhibition of chondrocytes pyroptosis could slow down the progression of OA. Our work aimed to explore the specific mechanisms and ways of regulating this process.

Design: In this work, the level of N⁶-methyladenosine (m⁶A) in clinical tissues was detected by ribonucleic acid (RNA) m⁶A dot blot. qRT-PCR (quantitative real-time polymerase chain reaction) was used to detect the messenger RNA (mRNA) expression level of m⁶A modified enzyme in clinical tissues. MTT (3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromid) and flow cytometry were used to detect the effect of sh-METTL3 (methyltransferase like 3) and NIMA-related kinase 7 (NEK7) transfection on chondrocytes pyroptosis in OA. Western blot was used to detect the protein expression levels of pyroptosis-related proteins. ELISA (enzyme-linked immunosorbent assay) was used to measure the protein concentration of inflammatory cytokines. The SRAMP online database was used to predict the m⁶A site of NEK7. HE staining was used to assess the progression of OA in mice.

Results: The level of m⁶A in clinical samples of OA patients was higher, and METTL3 was significantly higher expressed in clinical samples of OA patients. We provided evidence that low expression of METTL3 inhibited chondrocytes pyroptosis. In addition, Rescue experiments and in vivo experiments had shown that METTL3 in combination with NEK7 inhibited the progression of OA by promoting chondrocytes pyroptosis.

Conclusions: METTL3 regulates m⁶A modification of NEK7 and inhibits OA progression.

Objective: Extrachromosomal circular DNA (eccDNA) has been shown to be involved in several physiological and pathological processes including immunity, inflammation, aging, and tumor. However, the expression of eccDNA in cartilage has not been reported until now. In this study, we aimed to investigate the landscape of eccDNA in articular cartilage and analyze the potential roles in osteoarthritis (OA).

Methods: The samples of articular cartilage were obtained from total knee arthroplasty (TKA) donors with OA. The mitochondrial DNA (mtDNAs) and the linear DNAs from chondrocytes of articular cartilage were removed. Then the eccDNAs were enriched for cir-DNA sequencing. After quality control evaluation, we systematically revealed the identified eccDNA data including size distribution, the size range, and sequence pattern. Moreover, we explored and discussed the potential roles of eccDNA in OA via motif analysis and Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.

Results: The chondrocytes from OA cartilage contained an abundance of eccDNAs, which was termed as OC-eccDNAs (OA cartilage-derived eccDNA). The characteristics of OC-eccDNAs were tissue-specific, including the distribution, the size range, and sequence pattern. Moreover, the functional analysis indicated that eccDNA may be involved in the homeostasis maintenance of chondrocytes and participated in the process of OA.

Conclusions: Our data first showed the landscape of eccDNA in articular cartilage and preliminarily indicated the potential roles of eccDNA in OA.

Objective: Treatment strategies for osteochondral defects, for which particulated autologous cartilage transplantation (PACT) is an emerging treatment strategy, aim to restore the structure and function of the hyaline cartilage. Herein, we compared the efficacy of PACT with control or human transforming growth factor-β (rhTGF-β), and clarified the necessity of bone graft (BG) with PACT to treat shallow osteochondral defects in a porcine model.

Design: Two skeletally mature male micropigs received 4 osteochondral defects in each knee. The 16 defects were randomized to (1) empty control, (2) PACT, (3) PACT with BG, or (4) rhTGF-β. Animals were euthanized after 2 months and histomorphometry, immunofluorescence analysis, semiquantitative evaluation (O'Driscoll score), and magnetic resonance observation of cartilage repair tissue (MOCART) score were performed.

Results: Hyaline cartilages, glycosaminoglycan synthesis, and collagen type II staining were more abundant in the PACT than in the control and rhTGF-β groups. The O'Driscoll score was significantly different between groups (P < 0.001), with both PACT groups showing superiority (P = 0.002). PACT had the highest score (P = 0.002), with improved restoration of subchondral bone compared with PACT with BG. The MOCART score showed significant differences between groups (P = 0.021); MOCART and O'Driscoll scores showed high correlation (r = 0.847, P < 0.001).

Conclusion: Treatment of osteochondral defects with PACT improved tissue quality compared with that with control or rhTGF-β in a porcine model. BG, in addition to PACT, may be unnecessary for shallow osteochondral defects. Clinical Relevance. BG may not be necessary while performing PACT.

Introduction: The use of autologous human primary articular chondrocytes (hPACs) for repairing damaged cartilage is the golden standard; however, their 2-dimensional (2D) expansion induces dedifferentiation, making it challenging to create hyaline cartilage. Spinner flasks are efficient for generating cartilage organoids, allowing hPACs to proliferate without dedifferentiation; however, porcine notochordal cell-derived matrix (NCM) is needed for aggregation, limiting clinical application. Human articular chondroprogenitor cells (hACPCs) can be expanded many fold while maintaining chondrogenic potential. Therefore, the scalable production of hACPC cartilage organoids without NCM in spinner flasks was investigated in this study.

Methods: hPAC organoids with NCM and hACPC organoids using bone morphogenetic protein 9 (BMP-9) were produced in spinner flasks in 14 days. Thereafter, approximately 20 organoids were fused in low adhesive wells for 21 days. Organoids underwent mechanical testing, and both organoids and fused constructs were evaluated using biochemical, histological, and immunohistochemical analysis.

Results: The hACPCs self-assembled and synthesized abundant extracellular matrix once stimulated with BMP-9. The hPAC and hACPC organoids showed similar mechanical properties, but hACPC organoids and fused constructs showed a more uniform matrix and cell distribution.

Conclusion: The hACPC organoids fused into a neo-hyaline cartilage-like tissue, demonstrating their potential for improved, scalable cartilage tissue repair.

Background: Accurate donor-recipient matching of the femoral condyle radius of curvature (ROC) in osteochondral allograft (OCA) transplantation may aid in minimizing articular surface incongruities. Matching linear femorotibial dimensions, such as the femoral condyle anterior-posterior length (APL), femoral condyle width (lateral-medial length, LML), femoral hemicondyle width (HCW), and tibial plateau width (TPW), can provide similar results if they correlate well with ROC. This study investigates the relationship between femorotibial dimensions and ROC at the cartilage surface using magnetic resonance imaging (MRI).

Methods: Deidentified MRI images of 63 patients (35 men, 33 ± 10 years old, and 28 women, 27 ± 8 years old) were analyzed. Axial images were used for APL, LML, and TPW (TPW-Ax) measurements, while coronal images were used for HCW and TPW (TPW-Cor) measurements. Cartilage was segmented in true sagittal images at the medial femoral condyle (MFC) and lateral femoral condyle (LFC) to calculate their specific cartilage surface ROCs. Linear regression models were used to determine the relationship between the femorotibial dimensions and ROC.

Results: Cartilage ROC was significantly correlated with all the linear femorotibial dimensions at the MFC (P < 0.01, R² = 0.78, 0.69, 0.67, 0.59, and 0.37 for ROC correlations with APL, LML, TPW-Ax, TPW-Cor, and HCW, respectively), and the LFC (P < 0.01, R² = 0.81, 0.61, 0.56, 0.54, and 0.41 for ROC correlations with APL, LML, TPW-Ax, TPW-Cor, and HCW, respectively).

Conclusions: The APL was the most predictive femorotibial dimension of the cartilage surface ROC. Donor-recipient APL matching in OCA transplantation may provide a similar level of matching to that achievable by direct ROC measurements. The APL matching may help reduce cartilage incongruities, particularly for patients with large osteochondral lesions, in which the ROC measurement cannot be accurately determined.