scholarly journals Kelainan Matriks Ekstraseluler Agrekan pada Osteoarthritis

2020 ◽  
Vol 9 (1) ◽  
pp. 67-80
Author(s):  
Umiatin Umiatin ◽  
Jeanne A Diwinata Pawitan
Keyword(s):  
Extracellular Matrix ◽  
Enzyme Activity ◽  
Molecular Mechanisms ◽  
Cartilage Damage ◽  
Type Ii Collagen ◽  
Joint Disease ◽  
Joint Cartilage ◽  
Keywords Osteoarthritis ◽  
A Disintegrin And Metalloproteinase ◽  
Thrombospondin Motif

Abstrak Osteoarthritis (OA) merupakan penyakit sendi dengan prevalensi paling tinggi yang menyebabkan nyeri kronis dan disabilitas. Berbagai faktor antara lain faktor mekanik, biokimia dan faktor enzimatik berperan dalam perkembangan OA. Perkembangan OA dicirikan oleh degradasi berlebihan pada agrekan dalam matriks ekstraseluler tulang rawan sendi. Agrekan berfungsi menyediakan fleksibilitas, viskoelastisitas dan kompresibilitas jaringan. Struktur agrekan tidak konstan sepanjang hidup, namun mengalami perubahan yang disebabkan oleh aktivitas sintesis maupun degradasi. Degradasi agrekan merupakan penanda awal kerusakan tulang rawan sendi pada OA, yang diikuti oleh kerusakan kolagen tipe II. Sejauh ini mekanisme molekulernya belum diketahui pasti, sehingga diperlukan penelitian lebih lanjut mengenai mekanisme dan penyebab kerusakan agrekan. Tulisan ini merupakan suatu kajian naratif berdasarkan artikel dari jurnal nasional dan internasional yang bertujuan untuk memberikan informasi mengenai agrekan meliputi struktur, fungsi, dan faktor-faktor yang berperan pada perubahan struktur agrekan yang menginduksi terjadinya OA. Hasil kajian menunjukkan bahwa perubahan struktur agrekan erat kaitannya dengan perubahan fungsi mekanik tulang rawan sendi. Perubahan ini terjadi terutama karena degradasi yang disebabkan oleh aktivitas enzim, dari keluarga matriks metalloprotease (MMP) dan a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS). Dari kajian ini disimpulkan bahwa degradasi agrekan karena aktivitas enzim berperan penting dalam perkembangan OA, sehingga perlu dilakukan penelitian untuk mencari inhibitor enzim MMP dan ADAMTS sebagai agen terapeutik untuk menghambat perkembangan dan progresivitas OA. Kata kunci: osteoarthritis, matriks ektraseluler, agrekan, degradasi. Abstract Osteoarthritis (OA) is a joint disease with the highest prevalence and a major cause of chronic pain and disability. Many factors such as mechanical, biochemical, and enzymatic factors are involved in OA development. The development of OA is characterized by excessive degradation of aggrecan in the extracellular matrix of articular cartilage, which functions to provide flexibility, viscoelasticity, and tissue compressibility. The structure of aggrecan is not constant throughout life but undergoes changes caused by synthesis and degradation activities. Aggrecan degradation is an early marker of joint cartilage damage in OA, followed by type II collagen damage. However, the molecular mechanisms are not completely understood, so further research is needed on the mechanisms and causes of aggrecan damage. Here we provide a narrative review based on articles from national and international journals to describe the structure, function, and factors that contribute to the degradation of aggrecan. The results of the study show that changes in the structure of aggrecan are closely related to changes in the mechanical function of joint cartilage. This change occurs mainly due to degradation caused by enzyme activity, a family of matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS). The present study concludes that aggrecan degradation caused by enzyme activity was very crucial in the development of OA, it was needed to find MMP and ADAMTS inhibitors as a therapeutic agent to prevent the development and progression of OA. Keywords: osteoarthritis, extracellular matrix, aggrecan, degradation

scholarly journals Rat Chondrocyte Inflammation and Osteoarthritis Are Ameliorated by Madecassoside

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Safwat Adel Abdo Moqbel ◽  
Yuzhe He ◽  
Langhai Xu ◽  
Chiyuan Ma ◽  
Jisheng Ran ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Centella Asiatica ◽  
Type Ii Collagen ◽  
Cartilage Degeneration ◽  
Treated Group ◽  
Joint Disease ◽  
Inflammatory Factors ◽  
Protective Effects ◽  
Osteoarthritic Chondrocytes

As a joint disease, osteoarthritis (OA) is caused by the breakdown of subchondral bone and cartilage damage. Inflammatory factors, such as interleukin- (IL-) 1β, mediate the progression of OA. Madecassoside (MA), a triterpenoid component derived from the gotu kola herb (Centella asiatica), exhibits various pharmacological effects, including antioxidative and anti-inflammatory properties. In the present study, the protective effects and possible mechanism of MA on the treatment of OA were investigated. MA was demonstrated to significantly suppress the IL-1β-induced overexpression of matrix metalloproteinase- (MMP-) 3, MMP-13, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) and to decrease the IL-1β-induced degradation of type II collagen and sox9. Additionally, MA was able to reduce the IL-1β-induced phosphorylation of p65 in osteoarthritic chondrocytes. Furthermore, in a rat OA model, MA prevented cartilage degeneration and reduced the OARSI score in the MA-treated group compared with the OA group. The present study showed that MA suppresses the nuclear factor-κB signaling pathway, reducing IL-1β-induced chondrocyte inflammation, which indicates the therapeutic potential of MA in patients with OA.

scholarly journals Undenatured Type II Collagen Ameliorates Inflammatory Responses and Articular Cartilage Damage in the Rat Model of Osteoarthritis

2021 ◽  
Vol 8 ◽  
Author(s):  
Cemal Orhan ◽  
Vijaya Juturu ◽  
Emre Sahin ◽  
Mehmet Tuzcu ◽  
Ibrahim Hanifi Ozercan ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Inflammatory Responses ◽  
Cartilage Damage ◽  
Joint Inflammation ◽  
Type Ii Collagen ◽  
Serum Levels ◽  
Joint Disease ◽  
Type Ii ◽  
Age Related ◽  
Undenatured Type Ii Collagen

Osteoarthritis (OA) is an age-related joint disease that includes gradual disruption of the articular cartilage and the resulting pain. The present study was designed to test the effects of undenatured type II collagen (UC-II®) on joint inflammation in the monoiodoacetate (MIA) OA model. We also investigated possible mechanisms underlying these effects. Female Wistar rats were divided into three groups: (i) Control; (ii) MIA-induced rats treated with vehicle; (iii) MIA-induced rats treated with UC-II (4 mg/kg BW). OA was induced in rats by intra-articular injection of MIA (1 mg) after seven days of UC-II treatment. UC-II reduced MIA-induced Kellgren-Lawrence scoring (53.3%, P < 0.05). The serum levels of inflammatory cytokines [IL-1β (7.8%), IL-6 (18.0%), TNF-α (25.9%), COMP (16.4%), CRP (32.4%)] were reduced in UC-II supplemented group (P < 0.0001). In the articular cartilage, UC-II inhibited the production of PGE2 (19.6%) and the expression of IL-1β, IL-6, TNF-a, COX-2, MCP-1, NF-κB, MMP-3, RANKL (P < 0.001). The COL-1 and OPG levels were increased, and MDA decreased in UC-II supplemented rats (P < 0.001). UC-II could be useful to alleviate joint inflammation and pain in OA joints by reducing the expression of inflammatory mediators.

scholarly journals MicroRNAs and Osteoarthritis

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 92 ◽  
Author(s):  
Charles Malemud
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Articular Cartilage ◽  
Extracellular Matrix Proteins ◽  
Type Ii Collagen ◽  
Matrix Proteins ◽  
Chondrocyte Apoptosis ◽  
A Disintegrin And Metalloproteinase ◽  
Chondrocyte Signaling

An imbalance in gene expressional events skewing chondrocyte anabolic and catabolic pathways toward the latter causes an aberrant turnover and loss of extracellular matrix proteins in osteoarthritic (OA) articular cartilage. Thus, catabolism results in the elevated loss of extracellular matrix proteins. There is also evidence of an increase in the frequency of chondrocyte apoptosis that compromises the capacity of articular cartilage to undergo repair. Although much of the fundamental OA studies over the past 20 years identified and characterized many genes relevant to pro-inflammatory cytokines, apoptosis, and matrix metalloproteinases (MMPs)/a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS), more recent studies focused on epigenetic mechanisms and the associated role of microRNAs (miRs) in regulating gene expression in OA cartilage. Thus, several miRs were identified as regulators of chondrocyte signaling pathways, apoptosis, and proteinase gene expression. For example, the reduced expression of miR-146a was found to be coupled to reduced type II collagen (COL2) in OA cartilage, whereas MMP-13 levels were increased, suggesting an association between MMP-13 gene expression and COL2A1 gene expression. Results of these studies imply that microRNAs could become useful in the search for diagnostic biomarkers, as well as providing novel therapeutic targets for intervention in OA.

scholarly journals Chondroitin 6-Sulfation Regulates Perineuronal Net Formation by Controlling the Stability of Aggrecan

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Shinji Miyata ◽  
Hiroshi Kitagawa
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulfate ◽  
Neural Plasticity ◽  
Adult Brain ◽  
Chondroitin Sulfate Proteoglycans ◽  
Perineuronal Nets ◽  
Perineuronal Net ◽  
A Disintegrin And Metalloproteinase ◽  
The Stability ◽  
Thrombospondin Motif

Perineuronal nets (PNNs) are lattice-like extracellular matrix structures composed of chondroitin sulfate proteoglycans (CSPGs). The appearance of PNNs parallels the decline of neural plasticity, and disruption of PNNs reactivates neural plasticity in the adult brain. We previously reported that sulfation patterns of chondroitin sulfate (CS) chains on CSPGs influenced the formation of PNNs and neural plasticity. However, the mechanism of PNN formation regulated by CS sulfation remains unknown. Here we found that overexpression of chondroitin 6-sulfotransferase-1 (C6ST-1), which catalyzes 6-sulfation of CS chains, selectively decreased aggrecan, a major CSPG in PNNs, in the aged brain without affecting other PNN components. Both diffuse and PNN-associated aggrecans were reduced by overexpression of C6ST-1. C6ST-1 increased 6-sulfation in both the repeating disaccharide region and linkage region of CS chains. Overexpression of 6-sulfation primarily impaired accumulation of aggrecan in PNNs, whereas condensation of other PNN components was not affected. Finally, we found that increased 6-sulfation accelerated proteolysis of aggrecan by a disintegrin and metalloproteinase domain with thrombospondin motif (ADAMTS) protease. Taken together, our results indicate that sulfation patterns of CS chains on aggrecan influenced the stability of the CSPG, thereby regulating formation of PNNs and neural plasticity.

scholarly journals Baicalin Promotes Chondrocyte Viability and the Synthesis of Extracellular Matrix through TGF-β/Smad3 Pathway in Mouse Chondrocytes

2021 ◽  
Author(s):  
Pengzhen Wang ◽  
Shaoheng Zhang ◽  
Chaosheng Yu ◽  
Xifeng Xiong ◽  
Aiguo Li ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Nuclear Translocation ◽  
Type Ii Collagen ◽  
The Elderly ◽  
Joint Disease ◽  
Down Regulation ◽  
Chondrocyte Viability ◽  
Scutellaria Baicalensis Georgi ◽  
Smad3 Phosphorylation ◽  
Flavonoid Monomer

Abstract Background: Osteoarthritis (OA) is epidemic in the elderly people as a common chronic joint disease. By now, drug and surgical treatments are two main therapies for OA worldwidely. Baicalin (BA) is a flavonoid monomer extracted from Scutellaria baicalensis Georgi and is reported that BA has anti-inflammatory, anti-deformation and anti-bacterial effects. Methods: Micromass culture, alcian blue and Safran O (SO)/fast green staining were used to investigate chondrocyte viability and ECM synthesis in chondrocytes of all groups. The expression of SOX9 and Smad3 in chondrocytes of all groups were detected by western blot and RT-qPCR, the expression of aggrecan (AGG), type II collagen (Col2α), MMP9/13 and ADAMTS5 were detected by RT-qPCR. In current study, we demonstrated that BA neutralized the down-regulation of chondrocyte viability and extracellular matrix (ECM) secretion, including AGG and Col2α, induced by IL-1β. As the key regulators of ECM, the down-regulation of SOX9, and the up-regulation of MMP9/13 and ADAMTS5 induced by IL-1β were abolished by BA. Moreover, BA increased the nuclear translocation and phosphorylation of Smad3, one key mediator of TGF-β/Smads pathway. Interestingly, the addition of Smad3 inhibitor SIS3 reversed the promotions of BA on chondrocyte viability, ECM secretion, SOX9 expression, Smad3 nuclear translocation and Smad3 phosphorylation, and the down-regulation of BA on the expressions of MMP9/13 and ADAMTS5. Conclusions: These results imply that BA can protect chondrocytes against IL-1β-induced inflammatory injury through the acceleration of Smad3 phosphorylation and nuclear translocation in chondrocytes. This study demonstrates that BA may be a potential drug for OA clinical treatment.

Self-immobilization of coacervate droplets by enzyme-mediated hydrogelation

2021 ◽  
Author(s):  
Yufeng Chen ◽  
Yan-Wen Zhang ◽  
Mei Li ◽  
Songyang Liu ◽  
Xiaohai Yang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Enzyme Activity ◽  
The Self

An artificial protocell model mimicking stimuli-triggered extracellular matrix formation is demonstrated based on the self-immobilization of coacervate microdroplets. Endogenous enzyme activity within the microdroplets results in the release of Ca2+...

scholarly journals Molecular Mechanisms of Fetal Tendon Regeneration Versus Adult Fibrous Repair

2021 ◽  
Vol 22 (11) ◽  
pp. 5619
Author(s):  
Iris Ribitsch ◽  
Andrea Bileck ◽  
Alexander D. Aldoshin ◽  
Maciej M. Kańduła ◽  
Rupert L. Mayer ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Tendon Healing ◽  
Tendon Injury ◽  
Inflammatory Factors ◽  
Large Animal ◽  
Post Injury ◽  
Tendon Regeneration ◽  
Large Animal Models

Tendinopathies are painful, disabling conditions that afflict 25% of the adult human population. Filling an unmet need for realistic large-animal models, we here present an ovine model of tendon injury for the comparative study of adult scarring repair and fetal regeneration. Complete regeneration of the fetal tendon within 28 days is demonstrated, while adult tendon defects remained macroscopically and histologically evident five months post-injury. In addition to a comprehensive histological assessment, proteome analyses of secretomes were performed. Confirming histological data, a specific and pronounced inflammation accompanied by activation of neutrophils in adult tendon defects was observed, corroborated by the significant up-regulation of pro-inflammatory factors, neutrophil attracting chemokines, the release of potentially tissue-damaging antimicrobial and extracellular matrix-degrading enzymes, and a response to oxidative stress. In contrast, secreted proteins of injured fetal tendons included proteins initiating the resolution of inflammation or promoting functional extracellular matrix production. These results demonstrate the power and relevance of our novel ovine fetal tendon regeneration model, which thus promises to accelerate research in the field. First insights from the model already support our molecular understanding of successful fetal tendon healing processes and may guide improved therapeutic strategies.

Cellular modulation by the elasticity of biomaterials

2016 ◽  
Vol 4 (1) ◽  
pp. 9-26 ◽  
Author(s):  
Fengxuan Han ◽  
Caihong Zhu ◽  
Qianping Guo ◽  
Huilin Yang ◽  
Bin Li
Keyword(s):  
Extracellular Matrix ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Matrix Elasticity ◽  
Recent Advances

The elasticity of the extracellular matrix has been increasingly recognized as a dominating factor of cell fate and activities. This review provides an overview of the general principles and recent advances in the field of matrix elasticity-dependent regulation of a variety of cellular activities and functions, the underlying biomechanical and molecular mechanisms, as well as the pathophysiological implications.

Abstract MP254: Decellularized Extracellular Matrix Hydrogel Lowers Fibrosis And Fibroblast Differentiation In Post-injury Mice Hearts Through Capg

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Xinming Wang ◽  
Samuel Senyo
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Smooth Muscle Actin ◽  
Growth Factor Receptor ◽  
Inhibitory Effect ◽  
Extracellular Proteins ◽  
Collagen Deposition ◽  
Post Injury ◽  
Capping Protein ◽  
Decellularized Extracellular Matrix

Hypothesis and objective: We hypothesize that transplantation of decellularized cardiac extracellular matrix (dECM) lowers fibrosis and fibroblast differentiation. In this study we investigated collagen deposition and fibroblast differentiation in post-MI hearts and heart explants of various stiffness after dECM hydrogel treatments. The objectives are 1) determining if dECM derived from fetal and adult porcine hearts reduces fibrosis in injured hearts; and 2) identifying specific signaling pathways that regulate fibroblasts differentiation induced by extracellular proteins. Methods: Porcine dECM was injected immediately after ligating coronary artery in P1 mice. Histology was conducted on day 7 post-myocardial infarction (MI). A mice ventricle explant model was used to investigate the molecular mechanisms. Results: We observed that fetal dECM treatment lowered fibrosis and fibroblast differentiation in post-MI hearts (Fig.1). Fibroblast differentiation as indicated by α-smooth muscle actin expression in vimentin or platelet derived growth factor receptor α positive cells showed an inhibitory effect of fetal dECM on fibroblast differentiation. Using a heart explant model of modulated microenvironment stiffness, we demonstrated that increasing tissue stiffness stimulates fibroblast differentiation and collagen deposition. Fetal dECM treatment, however, inhibited fibroblast differentiation induced by increasing microenvironment stiffness. Transcriptome analysis revealed that two cytoskeleton-related genes, macrophage capping protein (CAPG) and leupaxin (LPXN), are modulated by dECM treatments. Using cytoskeleton polymerization modulators and siRNA, we demonstrated that fetal dECM lowers fibroblast differentiation through CAPG.

scholarly journals Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiyuan Yan ◽  
Yingchi Zhang ◽  
Gaohong Sheng ◽  
Bowei Ni ◽  
Yifan Xiao ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Cartilage Damage ◽  
Cartilage Degradation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Therapeutic Effects ◽  
Exact Role

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

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