scholarly journals Histologically Confirmed Recellularization is a Key Factor that Affects Meniscal Healing in Immature and Mature Meniscal Tears

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenqiang Yan ◽  
Wenli Dai ◽  
Jin Cheng ◽  
Yifei Fan ◽  
Fengyuan Zhao ◽  
...  
Keyword(s):  
Cell Death ◽  
Femoral Condyle ◽  
Meniscal Repair ◽  
Region Of Interest ◽  
Cartilage Degeneration ◽  
Meniscal Tears ◽  
Matrix Deposition ◽  
Key Factor ◽  
Mature Group ◽  
Immature Group

Healing outcomes of meniscal repair are better in younger than in older. However, exact mechanisms underlying superior healing potential in younger remain unclear from a histological perspective. This study included 24 immature rabbits and 24 mature rabbits. Tears were created in the anterior horn of medial meniscus of right knee in each rabbit. Animals were sacrificed at 1, 3, 6, and 12 weeks postoperatively. We performed macroscopic and histological evaluations of post-meniscal repair specimens. Cells were counted within a region of interest to confirm cellularization at tear site in immature menisci. The width of cell death zone was measured to determine the region of cell death in mature menisci. Apoptosis was evaluated by TUNEL assay. Vascularization was assessed by CD31 immunofluorescence. The glycosaminoglycans and the types 1 and 2 collagen content was evaluated by calculating average optical density of corresponding histological specimens. Cartilage degeneration was also evaluated. Healing outcomes following untreated meniscal tears were superior in immature group. Recellularization with meniscus-like cell morphology was observed at tear edge in immature menisci. Superior recellularization was observed at meniscal sites close to joint capsule than at sites distant from the capsule. Recellularization did not occur at tear site in mature group; however, we observed gradual enlargement of cell death zone. Apoptosis was presented at 1, 3, 6, 12 weeks in immature and mature menisci after untreated meniscal tears. Vascularization was investigated along the tear edges in immature menisci. Glycosaminoglycans and type 2 collagen deposition were negatively affected in immature menisci. We observed glycosaminoglycan degradation in mature menisci and cartilage degeneration, specifically in immature cartilage of the femoral condyle. In conclusion, compared with mature rabbits, immature rabbits showed more robust healing response after untreated meniscal tears. Vascularization contributed to the recellularization after meniscal tears in immature menisci. Meniscal injury fundamentally alters extracellular matrix deposition.

scholarly journals POS0393 FIBRIN DEPOSITION IS AN ACTIVE TRIGGER OF CARTILAGE DEGENERATION IN RHEUMATOID ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 426.1-426
Author(s):  
T. Hügle ◽  
S. Nasi ◽  
D. Ehirchiou ◽  
P. Omoumi ◽  
A. So ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cartilage Damage ◽  
Cartilage Degeneration ◽  
Cartilage Explants ◽  
Fibrin Deposition ◽  
Qrt Pcr ◽  
Catabolic Genes ◽  
Key Factor ◽  
Calcific Deposits

Background:Fibrin(ogen) maintains inflammation in various disorders but has never been linked to cartilage damage in rheumatoid arthritis (RA) or other forms of inflammatory arthritis.Objectives:To investigate the role of fibrin deposition on cartilage integrity in arthritis.Methods:Fibrin deposition on knee cartilage was analyzed by immunohistochemistry in RA patients and in murine adjuvant-induced arthritis (AIA). In chondrocytes, fibrinogen expression (Fgα, Fgβ, Fgγ) and procoagulant activity were evaluated by qRT-PCR and turbidimetry respectively. Fibrin-induced catabolic genes were assessed by qRT-PCR in chondrocytes. Fibrin-mediated chondro-synovial adhesion (CSA) with subsequent cartilage tears was studied in co-cultures of human RA cartilage with autologous synoviocytes, in the AIA model, and by MRI. The link between fibrin and calcification was examined in human RA cartilage stained for calcific deposits and in vitro in fibrinogen-stimulated chondrocytes.Results:Fibrin deposition on cartilage correlated with the severity of cartilage damage in human RA explants and in AIA wildtype (WT) mice, while fibrinogen deficient (Fg-/-) mice were protected. Accordingly, fibrin upregulated catabolic enzymes (Adamts5 and Mmp13) in chondrocytes. Secondly, CSA was present in fibrin-rich and damaged cartilage in AIA WT but not in Fg-/- mice. In line, autologous human synoviocytes, cultured on RA cartilage explants, adhered exclusively to fibrin-positive degraded areas. Gadolinium-enhanced MRI of human joints showed contrast-enhancement along cartilage surface in RA patients but not in controls. Finally, fibrin co-localized with calcification in human RA cartilage and triggered chondrocyte mineralization inducing pro-calcification genes (Anx5, Pit1, Pc1) and cytokine (IL-6). Although at a much lesser extent, we observed similar fibrin-mediated mechanisms in osteoarthritis (OA).Conclusion:Fibrin deposition directly impacts on cartilage integrity via induction of catabolism, mechanical stress, and calcification. Potentially, fibrin is a key factor of cartilage damage occurring in RA as a secondary consequence of inflammation.Disclosure of Interests:None declared

scholarly journals Total Meniscus Reconstruction Using a Polymeric Hybrid-Scaffold: Combined with 3D-Printed Biomimetic Framework and Micro-Particle

Polymers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 1910
Author(s):  
Hun-Jin Jeong ◽  
Se-Won Lee ◽  
Myoung Wha Hong ◽  
Young Yul Kim ◽  
Kyoung Duck Seo ◽  
...  
Keyword(s):  
Shape Matching ◽  
Femoral Condyle ◽  
Immunohistochemical Analysis ◽  
Cartilage Degeneration ◽  
Patient Specific ◽  
Hybrid Scaffold ◽  
Meniscus Tissue ◽  
Cell Source ◽  
3D Printed ◽  
Meniscus Regeneration

The meniscus has poor intrinsic regenerative capability, and its injury inevitably leads to articular cartilage degeneration. Although there are commercialized off-the-shelf alternatives to achieve total meniscus regeneration, each has its own shortcomings such as individualized size matching issues and inappropriate mechanical properties. We manufactured a polycaprolactone-based patient-specific designed framework via a Computed Tomography scan images and 3D-printing technique. Then, we completed the hybrid-scaffold by combining the 3D-printed framework and mixture micro-size composite which consists of polycaprolactone and sodium chloride to create a cell-friendly microenvironment. Based on this hybrid-scaffold with an autograft cell source (fibrochondrocyte), we assessed mechanical and histological results using the rabbit total meniscectomy model. At postoperative 12-week, hybrid-scaffold achieved neo-meniscus tissue formation, and its shape was maintained without rupture or break away from the knee joint. Histological and immunohistochemical analysis results showed obvious ingrowth of the fibroblast-like cells and chondrocyte cells as well as mature lacunae that were embedded in the extracellular matrix. Hybrid-scaffolding resulted in superior shape matching as compared to original meniscus tissue. Histological analysis showed evidence of extensive neo-meniscus cell ingrowth. Additionally, the hybrid-scaffold did not induce osteoarthritis on the femoral condyle surface. The 3D-printed hybrid-scaffold may provide a promising approach that can be applied to those who received total meniscal resection, using patient-specific design and autogenous cell source.

Isolated meniscus injuries in skeletally immature children and adolescents: state of the art

2021 ◽  
pp. jisakos-2020-000496
Author(s):  
Gustavo Vinagre ◽  
Flávio Cruz ◽  
Khalid Alkhelaifi ◽  
Pieter D'Hooghe
Keyword(s):  
Children And Adolescents ◽  
State Of The Art ◽  
Surgical Techniques ◽  
Meniscal Repair ◽  
Management Plan ◽  
Anatomical Location ◽  
Return To Sports ◽  
Meniscal Tears ◽  
Geographical Differences ◽  
Meniscal Healing

The prevalence of isolated meniscal injuries in children and adolescents is low; however, we see an increase mainly due to intensified sports-related activities at an early age. A meniscal repair should be attempted whenever possible as children present with increased meniscal healing potential. The diagnosis and management of meniscal tears involve both patient factors and tear characteristics: size, anatomical location and associated injuries. Special attention should be given to the feature of discoid menisci and related tears as they require a specific management plan. This state-of-the-art review highlights the most recent studies on clinical evaluation, surgical techniques, tips and tricks, pitfalls, outcomes, return-to-sports, geographical differences and future perspectives related to meniscal injuries in children and adolescents.

scholarly journals sFasL—The Key to a Riddle: Immune Responses in Aging Lung and Disease

2021 ◽  
Vol 22 (4) ◽  
pp. 2177
Author(s):  
Shulamit B. Wallach-Dayan ◽  
Dmytro Petukhov ◽  
Ronit Ahdut-HaCohen ◽  
Mark Richter-Dayan ◽  
Raphael Breuer
Keyword(s):  
Cell Death ◽  
Lung Disease ◽  
Fas Ligand ◽  
Death Receptor ◽  
Mesenchymal Cells ◽  
Soluble Form ◽  
Cell Accumulation ◽  
Key Factor ◽  
Aged Subjects

By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL+ T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment.

Long-Term Outcome After Arthroscopic Meniscal Repair Versus Arthroscopic Partial Meniscectomy for Traumatic Meniscal Tears

2010 ◽  
Vol 38 (8) ◽  
pp. 1542-1548 ◽  
Author(s):  
Thomas Stein ◽  
Andreas Peter Mehling ◽  
Frederic Welsch ◽  
Rüdige von Eisenhart-Rothe ◽  
Alwin Jäger
Keyword(s):  
Meniscal Repair ◽  
Partial Meniscectomy ◽  
Meniscal Tears ◽  
Arthroscopic Partial Meniscectomy ◽  
Term Outcome ◽  
Long Term Outcome

scholarly journals Return to Play After Isolated Meniscal Repairs in Athletes: A Systematic Review

2020 ◽  
Vol 8 (11) ◽  
pp. 232596712096209
Author(s):  
Erica R. Blanchard ◽  
Christopher J. Hadley ◽  
Eric D. Wicks ◽  
William Emper ◽  
Steven B. Cohen
Keyword(s):  
Systematic Review ◽  
Data Extraction ◽  
Cruciate Ligament ◽  
Meniscal Repair ◽  
Return To Play ◽  
Meniscal Tears ◽  
Arthroscopic Technique ◽  
Level Of Evidence ◽  
Study Results ◽  
Anterior Cruciate

Background: Meniscal tears are a common knee injury. Isolated meniscal tears are less common; however, unaddressed tears can be troublesome, particularly for athletes. There is currently a lack of data in the literature on athletes returning to play after isolated meniscal repair. Purpose: To evaluate the return to play rate and time to return to play for athletes with isolated meniscal injuries. Study Design: Systematic review; Level of evidence, 4. Methods: A search of the PubMed, EMBASE, and Cochrane electronic databases was conducted to identify studies that reported the time and the rate of return to play in athletes after repair of isolated meniscal tears. Studies were excluded if there was a concomitant anterior cruciate ligament reconstruction, if there was a meniscectomy instead of a meniscal repair, or if the study was a systematic review. Quality assessment and data extraction were performed by 2 examiners. Results: Overall, 21 studies were included in this review. There were 355 athletes (358 knees) with a mean age of 22.5 years (range, 9-68 years). A sex breakdown was noted in 16 of the 21 (76.2%) studies with 224 men and 71 women. The specific repair technique was described in 259 (72.3%) knees. Of the total knees, 109 (30.4%) had an open repair, 128 (35.8%) had an inside-out arthroscopic technique repair, and 22 (6.1%) had an all-inside arthroscopic technique repair. Complications were addressed in 11 studies, with 13 out of 155 (8.4%) patients across the 11 articles having a postoperative complication. Of the total 355 patients, 295 (83.1%) returned to play, and 17 of these 21 (81.0%) articles reported the time it took for athletes to return to play, with a mean return of 8.7 months. Conclusion: The study results indicate that return to play rates after isolated meniscal repair are high, with an overall return to play rate of 83.1% and a mean return to play time of 8.7 months. However, the limited number of studies, particularly ones with larger patient numbers, highlights the need for further investigation regarding isolated meniscal repair in athletes.

microRNA-181a-5p antisense oligonucleotides attenuate osteoarthritis in facet and knee joints

2018 ◽  
Vol 78 (1) ◽  
pp. 111-121 ◽  
Author(s):  
Akihiro Nakamura ◽  
Yoga Raja Rampersaud ◽  
Sayaka Nakamura ◽  
Anirudh Sharma ◽  
Fanxing Zeng ◽  
...  
Keyword(s):  
Cell Death ◽  
Antisense Oligonucleotides ◽  
Apoptotic Cell ◽  
Cartilage Degeneration ◽  
Apoptotic Cell Death ◽  
Knee Joints ◽  
Protective Effects ◽  
Knee Oa ◽  
Articular Cartilage Degeneration

ObjectivesWe recently identified microRNA-181a-5p (miR-181a-5p) as a critical mediator involved in the destruction of lumbar facet joint (FJ) cartilage. In this study, we tested if locked nucleic acid (LNA) miR-181a-5p antisense oligonucleotides (ASO) could be used as a therapeutic to limit articular cartilage degeneration.MethodsWe used a variety of experimental models consisting of both human samples and animal models of FJ and knee osteoarthritis (OA) to test the effects of LNA-miR-181a-5p ASO on articular cartilage degeneration. Histopathological analysis including immunohistochemistry and in situ hybridisation were used to detect key OA catabolic markers and microRNA, respectively. Apoptotic/cell death markers were evaluated by flow cytometry. qPCR and immunoblotting were applied to quantify gene and protein expression.ResultsmiR-181a-5p expression was increased in human FJ OA and knee OA cartilage as well as injury-induced FJ OA (rat) and trauma-induced knee OA (mouse) cartilage compared with control cartilage, correlating with classical OA catabolic markers in human, rat and mouse cartilage. We demonstrated that LNA-miR-181a-5p ASO in rat and mouse chondrocytes reduced the expression of cartilage catabolic and chondrocyte apoptotic/cell death markers in vitro. Treatment of OA-induced rat FJ or mouse knee joints with intra-articular injections of in vivo grade LNA-miR-181a-5p ASO attenuated cartilage destruction, and the expression of catabolic, hypertrophic, apoptotic/cell death and type II collagen breakdown markers. Finally, treatment of LNA-miR-181a-5p ASO in cultures of human knee OA chondrocytes (in vitro) and cartilage explants (ex vivo) further demonstrated its cartilage protective effects.ConclusionsOur data demonstrate, for the first time, that LNA-miR-181a-5p ASO exhibit cartilage-protective effects in FJ and knee OA.

scholarly journals Characterization of Synovial Cytokine Patterns in Bucket-Handle and Posterior Horn Meniscal Tears

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Marco Turati ◽  
Davide Maggioni ◽  
Nicolò Zanchi ◽  
Marta Gandolla ◽  
Massimo Gorla ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Meniscal Tear ◽  
Meniscal Repair ◽  
Posterior Horn ◽  
Meniscal Tears ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Tear Pattern ◽  
Cytokine Responsiveness ◽  
Bucket Handle

The specific etiology of meniscal tears, including the mechanism of lesion, location, and orientation, is considered for its contribution to subsequent joint cytokine responsiveness, healing outcomes, and by extension, appropriate lesion-specific surgical remediation. Meniscal repair is desirable to reduce the probability of development of posttraumatic osteoarthritis (PTOA) which is strongly influenced by the coordinate generation of pro- and anti-inflammatory cytokines by the injured cartilage. We now present biochemical data on variation in cytokine levels arising from two particular meniscal tears: bucket-handle (BH) and posterior horn (PH) isolated meniscal tears. We selected these two groups due to the different clinical presentations. We measured the concentrations of TNF-α, IL-1β, IL-6, IL-8, and IL-10 in knee synovial fluid of 45 patients with isolated meniscal lesions (BH tear, n = 12 ; PH tear, n = 33 ). TNF-α levels were significantly ( p < 0.05 ) greater in the BH group compared with the PH group, whereas IL-1β levels were significantly greater ( p < 0.05 ) in the PH group compared with the BH group. Both BH and PH groups were consistent in presenting a positive correlation between concentrations of IL-6 and IL-1β. A fundamental difference in IL-10 responsiveness between the two groups was noted; specifically, levels of IL-10 were positively correlated with IL-6 in the BH group, whereas in the PH group, levels of IL-10 were positively correlated with IL-1β. Collectively, our data suggest a possible influence of the meniscal tear pattern to the articular cytokine responsiveness. This differential expression of inflammatory cytokines may influence the risk of developing PTOA in the long term.

Ultrastructural Imaging Analysis of the Zona Pellucida Surface in Bovine Oocytes

2019 ◽  
Vol 25 (4) ◽  
pp. 1032-1036 ◽  
Author(s):  
Francisco Báez ◽  
Álvaro A. Camargo ◽  
Gustavo D.A. Gastal
Keyword(s):  
Zona Pellucida ◽  
Ultrastructural Change ◽  
Early Embryo ◽  
Imaging Analysis ◽  
Mature Group ◽  
Immature Group ◽  
Imagej Software ◽  
Bovine Oocytes ◽  
Objective Methodology

AbstractThe aims of the present study were to: (i) evaluate the ultrastructural differences in the zona pellucida (ZP) surface between immature and mature bovine oocytes, and (ii) describe a new objective technique to measure the pores in the outer ZP. Intact cumulus–oocyte complexes (COCs) obtained from a local abattoir were immediately fixed (immature group) or submitted to in vitro maturation (IVM) at 38.5 °C for 24 h in a humidified atmosphere of 5% CO2 in air (mature group). Oocytes from both groups were morphologically evaluated via Scanning Electron Microscopy (SEM) and the images were processed in the Fiji/ImageJ software using a new objective methodology through the Trainable Weka Segmentation plugin. The average number of pores in ZP was greater (p < 0.05) in the mature group than the immature group. However, the size and circularity of pores in ZP did not differ (p > 0.05) between groups. In conclusion, it has been shown that the number of pores highlighted the main ultrastructural change in the morphology of the ZP surface of bovine oocytes during the IVM process. We have described an objective method that can be used to evaluate ultrastructural modifications of the ZP surface during oocyte maturation and early embryo development.

scholarly journals Mutant p53 and Cellular Stress Pathways: A Criminal Alliance That Promotes Cancer Progression

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 614 ◽  
Author(s):  
Gabriella D’Orazi ◽  
Mara Cirone
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Survival ◽  
Cellular Stress ◽  
Hypoxia Inducible Factor ◽  
Related Factor ◽  
Protective Mechanisms ◽  
Key Factor ◽  
The Unfolded Protein Response

The capability of cancer cells to manage stress induced by hypoxia, nutrient shortage, acidosis, redox imbalance, loss of calcium homeostasis and exposure to drugs is a key factor to ensure cancer survival and chemoresistance. Among the protective mechanisms utilized by cancer cells to cope with stress a pivotal role is played by the activation of heat shock proteins (HSP) response, anti-oxidant response induced by nuclear factor erythroid 2-related factor 2 (NRF2), the hypoxia-inducible factor-1 (HIF-1), the unfolded protein response (UPR) and autophagy, cellular processes strictly interconnected. However, depending on the type, intensity or duration of cellular stress, the balance between pro-survival and pro-death pathways may change, and cell survival may be shifted into cell death. Mutations of p53 (mutp53), occurring in more than 50% of human cancers, may confer oncogenic gain-of-function (GOF) to the protein, mainly due to its stabilization and interaction with the above reported cellular pathways that help cancer cells to adapt to stress. This review will focus on the interplay of mutp53 with HSPs, NRF2, UPR, and autophagy and discuss how the manipulation of these interconnected processes may tip the balance towards cell death or survival, particularly in response to therapies.

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