scholarly journals Urolithin A Protects Chondrocytes From Mechanical Overloading-Induced Injuries

2021 ◽  
Vol 12 ◽  
Author(s):  
Yuchen He ◽  
Lauren Yocum ◽  
Peter G Alexander ◽  
Michael J Jurczak ◽  
Hang Lin
Keyword(s):  
Compressive Loading ◽  
Cartilage Degeneration ◽  
Cell Types ◽  
Cartilage Degradation ◽  
Cartilage Matrix ◽  
Matrix Deposition ◽  
Mechanistic Analysis ◽  
Urolithin A ◽  
Dynamic Compressive Loading

Physiological mechanical stimulation has been shown to promote chondrogenesis, but excessive mechanical loading results in cartilage degradation. Currently, the underlying mechanotransduction pathways in the context of physiological and injurious loading are not fully understood. In this study, we aim to identify the critical factors that dictate chondrocyte response to mechanical overloading, as well as to develop therapeutics that protect chondrocytes from mechanical injuries. Specifically, human chondrocytes were loaded in hyaluronic hydrogel and then subjected to dynamic compressive loading under 5% (DL-5% group) or 25% strain (DL-25% group). Compared to static culture and DL-5%, DL-25% reduced cartilage matrix formation from chondrocytes, which was accompanied by the increased senescence level, as revealed by higher expression of p21, p53, and senescence-associated beta-galactosidase (SA-β-Gal). Interestingly, mitophagy was suppressed by DL-25%, suggesting a possible role for the restoration mitophagy in reducing cartilage degeneration with mechanical overloading. Next, we treated the mechanically overloaded samples (DL-25%) with Urolithin A (UA), a natural metabolite previously shown to enhance mitophagy in other cell types. qRT-PCR, histology, and immunostaining results confirmed that UA treatment significantly increased the quantity and quality of cartilage matrix deposition. Interestingly, UA also suppressed the senescence level induced by mechanical overloading, demonstrating its senomorphic potential. Mechanistic analysis confirmed that UA functioned partially by enhancing mitophagy. In summary, our results show that mechanical overloading results in cartilage degradation partially through the impairment of mitophagy. This study also identifies UA’s novel use as a compound that can protect chondrocytes from mechanical injuries, supporting high-quality cartilage formation/maintenance.

scholarly journals Kartogenin prevents cartilage degradation and alleviates osteoarthritis progression in mice via the miR-146a/NRF2 axis

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Mingzhuang Hou ◽  
Yijian Zhang ◽  
Xinfeng Zhou ◽  
Tao Liu ◽  
Huilin Yang ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Cartilage Matrix ◽  
Related Factor ◽  
Dependent Manner ◽  
Matrix Degradation ◽  
Protein Levels ◽  
Bone Sclerosis

AbstractOsteoarthritis (OA) is a common articular degenerative disease characterized by loss of cartilage matrix and subchondral bone sclerosis. Kartogenin (KGN) has been reported to improve chondrogenic differentiation of mesenchymal stem cells. However, the therapeutic effect of KGN on OA-induced cartilage degeneration was still unclear. This study aimed to explore the protective effects and underlying mechanisms of KGN on articular cartilage degradation using mice with post-traumatic OA. To mimic the in vivo arthritic environment, in vitro cultured chondrocytes were exposed to interleukin-1β (IL-1β). We found that KGN barely affected the cell proliferation of chondrocytes; however, KGN significantly enhanced the synthesis of cartilage matrix components such as type II collagen and aggrecan in a dose-dependent manner. Meanwhile, KGN markedly suppressed the expression of matrix degradation enzymes such as MMP13 and ADAMTS5. In vivo experiments showed that intra-articular administration of KGN ameliorated cartilage degeneration and inhibited subchondral bone sclerosis in an experimental OA mouse model. Molecular biology experiments revealed that KGN modulated intracellular reactive oxygen species in IL-1β-stimulated chondrocytes by up-regulating nuclear factor erythroid 2-related factor 2 (NRF2), while barely affecting its mRNA expression. Microarray analysis further revealed that IL-1β significantly up-regulated miR-146a that played a critical role in regulating the protein levels of NRF2. KGN treatment showed a strong inhibitory effect on the expression of miR-146a in IL-1β-stimulated chondrocytes. Over-expression of miR-146a abolished the anti-arthritic effects of KGN not only by down-regulating the protein levels of NRF2 but also by up-regulating the expression of matrix degradation enzymes. Our findings demonstrate, for the first time, that KGN exerts anti-arthritic effects via activation of the miR-146a-NRF2 axis and KGN is a promising heterocyclic molecule to prevent OA-induced cartilage degeneration.

Dynamic Compressive Loading and Crosslinking Density Influence the Chondrogenic and Hypertrophic Differentiation of Human Mesenchymal Stem Cells Seeded in Hyaluronic Acid Hydrogels

2012 ◽  
Author(s):  
Liming Bian ◽  
Robert L. Mauck ◽  
Jason A. Burdick
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hyaluronic Acid ◽  
Compressive Loading ◽  
Crosslinking Density ◽  
Cartilage Matrix ◽  
Human Mscs ◽  
Parathyroid Hormone Related Protein ◽  
And Cartilage ◽  
Dynamic Compressive Loading

While hyaluronic acid (HA) hydrogels provide a stable 3D environment that is conducive to the chondrogenesis of mesenchymal stem cells (MSCs) in the presence of growth factors [1], the neocartilage that is formed remains inferior to native tissue, even after long culture durations. Additionally, MSCs eventually transit into a hypertrophic phenotype after chondrogenic induction, resulting in the calcification of the ECM after ectopic transplantation [2]. From a material design perspective, variation in the HA hydrogel scaffold crosslinking density via changes in the HA macromer concentration can influence chondrogenesis of MSCs and neocartilage formation [3]. Recent studies have also demonstrated that dynamic compression enhances the expression of chondrogenic markers and cartilage matrix synthesis by MSCs encapsulated in various hydrogels, including agarose [4], alginate [5] and fibrin [6]. Furthermore, mechanical signals also regulate growth plate and articular cartilage chondrocyte hypertrophy via the IHH-PTHrP (India hedgehog, Parathyroid hormone-related protein) pathway [7]. In contrast to biologically inert scaffold materials, HA is capable of interacting with cells (including MSCs) via cell surface receptors (CD44, CD54, and CD168) [8; 9]. Therefore the objectives of this study were to (i) evaluate the effects of both hydrogel crosslinking and dynamic compressive loading on (i) chondrogenesis and cartilage matrix production/distribution of human MSCs encapsulated in HA gels and (ii) hypertrophic differentiation of human MSCs using an in vitro MSC hypertrophy model [10].

Texture dependencies on flow stress behavior of magnesium alloy under dynamic compressive loading

Vacuum ◽  
2021 ◽  
pp. 110323
Author(s):  
Faisal Nazeer ◽  
Syed Zohaib Hassan Naqvi ◽  
Abul Kalam ◽  
A.G. Al-Sehemi ◽  
Hussein Alrobi
Keyword(s):  
Flow Stress ◽  
Magnesium Alloy ◽  
Compressive Loading ◽  
Stress Behavior ◽  
Flow Stress Behavior ◽  
Dynamic Compressive Loading

scholarly journals Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yan Zhou ◽  
Jianghua Ming ◽  
Yaming Li ◽  
Bochun Li ◽  
Ming Deng ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Apoptotic Cell ◽  
Synovial Fibroblasts ◽  
Cartilage Degeneration ◽  
Cartilage Degradation ◽  
Exosomal Mirnas ◽  
Exosomal Mirna ◽  
And Control ◽  
And Cartilage

AbstractMicroRNAs (miRNAs) encapsulated within exosomes can serve as essential regulators of intercellular communication and represent promising biomarkers of several aging-associated disorders. However, the relationship between exosomal miRNAs and osteoarthritis (OA)-related chondrocytes and synovial fibroblasts (SFCs) remain to be clarified. Herein, we profiled synovial fluid-derived exosomal miRNAs and explored the effects of exosomal miRNAs derived from SFCs on chondrocyte inflammation, proliferation, and survival, and further assessed their impact on cartilage degeneration in a surgically-induced rat OA model. We identified 19 miRNAs within synovial fluid-derived exosomes that were differentially expressed when comparing OA and control patients. We then employed a microarray-based approach to confirm that exosomal miRNA-126-3p expression was significantly reduced in OA patient-derived synovial fluid exosomes. At a functional level, miRNA-126-3p mimic treatment was sufficient to promote rat chondrocyte migration and proliferation while also suppressing apoptosis and IL-1β, IL-6, and TNF-α expression. SFC-miRNA-126-3p-Exos were able to suppress apoptotic cell death and associated inflammation in chondrocytes. Our in vivo results revealed that rat SFC-derived exosomal miRNA-126-3p was sufficient to suppress the formation of osteophytes, prevent cartilage degeneration, and exert anti-apoptotic and anti-inflammatory effects on articular cartilage. Overall, our findings indicate that SFC exosome‐delivered miRNA-126-3p can constrain chondrocyte inflammation and cartilage degeneration. As such, SFC-miRNA-126-3p-Exos may be of therapeutic value for the treatment of patients suffering from OA.

scholarly journals PERITONEAL ADHESIONS TYPE I, III AND TOTAL COLLAGEN ON POLYPROPYLENE AND COATED POLYPROPYLENE MESHES: EXPERIMENTAL STUDY IN RATS

2017 ◽  
Vol 30 (2) ◽  
pp. 77-82 ◽  
Author(s):  
Lucas Félix ROSSI ◽  
Manoel Roberto Maciel TRINDADE ◽  
Armando José D`ACAMPORA ◽  
Luise MEURER
Keyword(s):  
Type I Collagen ◽  
Cell Types ◽  
Type Iii Collagen ◽  
Type I ◽  
Abdominal Adhesions ◽  
Peritoneal Adhesions ◽  
Type Iii ◽  
Total Collagen

ABSTRACT Background: Hernia correction is a routinely performed treatment in surgical practice. The improvement of the operative technique and available materials certainly has been a great benefit to the quality of surgical results. The insertion of prostheses for hernia correction is well-founded in the literature, and has become the standard of treatment when this type of disease is discussed. Aim: To evaluate two available prostheses: the polypropylene and polypropylene coated ones in an experimental model. Methods: Seven prostheses of each kind were inserted into Wistar rats (Ratus norvegicus albinus) in the anterior abdominal wall of the animal in direct contact with the viscera. After 90 days follow-up were analyzed the intra-abdominal adhesions, and also performed immunohistochemical evaluation and videomorphometry of the total, type I and type III collagen. Histological analysis was also performed with hematoxylin-eosin to evaluate cell types present in each mesh. Results: At 90 days the adhesions were not different among the groups (p=0.335). Total collagen likewise was not statistically different (p=0.810). Statistically there was more type III collagen in the coated polypropylene group (p=0.039) while type I was not different among the prostheses (p=0.050). The lymphocytes were statistically more present in the polypropylene group (p=0.041). Conclusion: The coated prosthesis was not different from the polypropylene one regarding the adhesion. Total and type I collagen were not different among the groups, while type III collagen was more present on the coated mesh. There was a greater number of lymphocytes on the polypropylene mesh.

scholarly journals Melanotic Neuroectodermal Tumor of Infancy: a Clinicopathological Case Report

2018 ◽  
Vol 29 (4) ◽  
pp. 400-404
Author(s):  
Patrícia Maria Fernandes ◽  
Rogério de Andrade Elias ◽  
Alan Roger Santos-Silva ◽  
André Caroli Rocha ◽  
Pablo Augustin Vargas ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cell Types ◽  
Neuroectodermal Tumor ◽  
Alveolar Ridge ◽  
Incisional Biopsy ◽  
Epithelioid Cells ◽  
Melanin Pigmentation ◽  
Immunohistochemical Analyses

Abstract Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that affects mainly children under 1 year of age. A 4-month-old boy was referred for evaluation of a lesion with 1 month of evolution. Intra-oral examination detected a firm upon palpation submucosal nodular mass, measuring 1.5 cm in diameter, affecting the anterior maxillary alveolar ridge and covered by a slightly blue mucosa with evident telangiectasia. The patient underwent an incisional biopsy and histological and immunohistochemical analyses revealed nests of AE1/AE3 positive epithelioid cells with abundant melanin pigmentation. Other cell types, resembling neuroblasts, were also present and positive for CD56, synaptophysin and enolase. The diagnosis of MNTI was established and the patient was referred for treatment. Conservative surgical resection was performed along with 3 adjacent teeth under general anesthesia. The patient is in follow-up for 1,5 year without recurrence. Conservative surgical management of MNTI may be an alternative to maxillectomy, contributing to the patient´s quality of life.

scholarly journals Prolactin inhibits the apoptosis of chondrocytes induced by serum starvation

2006 ◽  
Vol 189 (2) ◽  
pp. R1-R8 ◽  
Author(s):  
C Zermeño ◽  
J Guzmán-Morales ◽  
Y Macotela ◽  
G Nava ◽  
F López-Barrera ◽  
...  
Keyword(s):  
Articular Chondrocytes ◽  
Cell Types ◽  
Cartilage Degradation ◽  
Chondrocyte Apoptosis ◽  
Heat Inactivation ◽  
Serum Starvation ◽  
Endochondral Bone Formation ◽  
Endochondral Bone ◽  
Therapeutic Value ◽  
Apoptotic Effect

The apoptosis of chondrocytes plays an important role in endochondral bone formation and in cartilage degradation during aging and disease. Prolactin (PRL) is produced in chondrocytes and is known to promote the survival of various cell types. Here we show that articular chondrocytes from rat postpubescent and adult cartilage express the long form of the PRL receptor as revealed by immunohistochemistry of cartilage sections and by RT-PCR and Western blot analyses of the isolated chondrocytes. Furthermore, we demonstrate that PRL inhibits the apoptosis of these same chondrocytes cultured in low-serum. Chondrocyte apoptosis was measured by hypodiploid DNA content determined by flow cytometry and by DNA fragmentation evaluated by the ELISA and the TUNEL methods. The anti-apoptotic effect of PRL was dose-dependent and was prevented by heat inactivation. These data demonstrate that PRL can act as a survival factor for chondrocytes and that it has potential preventive and therapeutic value in arthropathies characterized by cartilage degradation.

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