Displaying publications 1 - 20 of 109 in total

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  1. Pingguan-Murphy B, Nawi I
    Clinics (Sao Paulo), 2012 Aug;67(8):939-44.
    PMID: 22948463
    OBJECTIVES: The promotion of extracellular matrix synthesis by chondrocytes is a requisite part of an effective cartilage tissue engineering strategy. The aim of this in vitro study was to determine the effect of bi-axial cyclic mechanical loading on cell proliferation and the synthesis of glycosaminoglycans by chondrocytes in three-dimensional cultures.

    METHOD: A strain comprising 10% direct compression and 1% compressive shear was applied to bovine chondrocytes seeded in an agarose gel during two 12-hour conditioning periods separated by a 12-hour resting period.

    RESULTS: The bi-axial-loaded chondrocytes demonstrated a significant increase in glycosaminoglycan synthesis compared with samples exposed to uni-axial or no loading over the same period (p<0.05). The use of a free-swelling recovery period prior to the loading regime resulted in additional glycosaminoglycan production and a significant increase in DNA content (p<0.05), indicating cell proliferation.

    CONCLUSIONS: These results demonstrate that the use of a bi-axial loading regime results in increased matrix production compared with uni-axial loading.

    Matched MeSH terms: Extracellular Matrix/genetics; Extracellular Matrix/metabolism*
  2. Nam HY, Pingguan-Murphy B, Abbas AA, Merican AM, Kamarul T
    Stem Cells Int, 2019;2019:9723025.
    PMID: 30918524 DOI: 10.1155/2019/9723025
    The present study was conducted to establish the amount of mechanical strain (uniaxial cyclic stretching) required to provide optimal tenogenic differentiation expression in human mesenchymal stromal cells (hMSCs) in vitro, in view of its potential application for tendon maintenance and regeneration. Methods. In the present study, hMSCs were subjected to 1 Hz uniaxial cyclic stretching for 6, 24, 48, and 72 hours; and were compared to unstretched cells. Changes in cell morphology were observed under light and atomic force microscopy. The tenogenic, osteogenic, adipogenic, and chondrogenic differentiation potential of hMSCs were evaluated using biochemical assays, extracellular matrix expressions, and selected mesenchyme gene expression markers; and were compared to primary tenocytes. Results. Cells subjected to loading displayed cytoskeletal coarsening, longer actin stress fiber, and higher cell stiffness as early as 6 hours. At 8% and 12% strains, an increase in collagen I, collagen III, fibronectin, and N-cadherin production was observed. Tenogenic gene expressions were highly expressed (p < 0.05) at 8% (highest) and 12%, both comparable to tenocytes. In contrast, the osteoblastic, chondrogenic, and adipogenic marker genes appeared to be downregulated. Conclusion. Our study suggests that mechanical loading at 8% strain and 1 Hz provides exclusive tenogenic differentiation; and produced comparable protein and gene expression to primary tenocytes.
    Matched MeSH terms: Extracellular Matrix
  3. Boyle ST, Mittal P, Kaur G, Hoffmann P, Samuel MS, Klingler-Hoffmann M
    J Proteome Res, 2020 10 02;19(10):4093-4103.
    PMID: 32870688 DOI: 10.1021/acs.jproteome.0c00511
    Tumorigenesis involves a complex interplay between genetically modified cancer cells and their adjacent normal tissue, the stroma. We used an established breast cancer mouse model to investigate this inter-relationship. Conditional activation of Rho-associated protein kinase (ROCK) in a model of mammary tumorigenesis enhances tumor growth and progression by educating the stroma and enhancing the production and remodeling of the extracellular matrix. We used peptide matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to quantify the proteomic changes occurring within tumors and their stroma in their regular spatial context. Peptides were ranked according to their ability to discriminate between the two groups, using a receiver operating characteristic tool. Peptides were identified by liquid chromatography tandem mass spectrometry, and protein expression was validated by quantitative immunofluorescence using an independent set of tumor samples. We have identified and validated four key proteins upregulated in ROCK-activated mammary tumors relative to those expressing kinase-dead ROCK, namely, collagen I, α-SMA, Rab14, and tubulin-β4. Rab14 and tubulin-β4 are expressed within tumor cells, whereas collagen I is localized within the stroma. α-SMA is predominantly localized within the stroma but is also expressed at higher levels in the epithelia of ROCK-activated tumors. High expression of COL1A, the gene encoding the pro-α 1 chain of collagen, correlates with cancer progression in two human breast cancer genomic data sets, and high expression of COL1A and ACTA2 (the gene encoding α-SMA) are associated with a low survival probability (COLIA, p = 0.00013; ACTA2, p = 0.0076) in estrogen receptor-negative breast cancer patients. To investigate whether ROCK-activated tumor cells cause stromal cancer-associated fibroblasts (CAFs) to upregulate expression of collagen I and α-SMA, we treated CAFs with medium conditioned by primary mammary tumor cells in which ROCK had been activated. This led to abundant production of both proteins in CAFs, clearly highlighting the inter-relationship between tumor cells and CAFs and identifying CAFs as the potential source of high levels of collagen 1 and α-SMA and associated enhancement of tissue stiffness. Our research emphasizes the capacity of MALDI-MSI to quantitatively assess tumor-stroma inter-relationships and to identify potential prognostic factors for cancer progression in human patients, using sophisticated mouse cancer models.
    Matched MeSH terms: Extracellular Matrix
  4. Lee SY, Pereira BP, Yusof N, Selvaratnam L, Yu Z, Abbas AA, et al.
    Acta Biomater, 2009 Jul;5(6):1919-25.
    PMID: 19289306 DOI: 10.1016/j.actbio.2009.02.014
    A poly(vinyl alcohol) (PVA) hydrogel composite scaffold containing N,O-carboxymethylated chitosan (NOCC) was tested to assess its potential as a scaffold for cartilage tissue engineering in a weight-bearing environment. The mechanical properties under unconfined compression for different hydration periods were investigated. The effect of supplementing PVA with NOCC (20wt.% PVA:5vol.% NOCC) produced a porosity of 43.3% and this was compared against a non-porous PVA hydrogel (20g PVA: 100ml of water, control). Under non-hydrated conditions, the porous PVA-NOCC hydrogel behaved in a similar way to the control non-porous PVA hydrogel, with similar non-linear stress-strain response under unconfined compression (0-30% strain). After 7days' hydration, the porous hydrogel demonstrated a reduced stiffness (0.002kPa, at 25% strain), resulting in a more linear stiffness relationship over a range of 0-30% strain. Poisson's ratio for the hydrated non-porous and porous hydrogels ranged between 0.73 and 1.18, and 0.76 and 1.33, respectively, suggesting a greater fluid flow when loaded. The stress relaxation function for the porous hydrogel was affected by the hydration period (from 0 to 600s); however the percentage stress relaxation regained by about 95%, after 1200s for all hydration periods assessed. No significant differences were found between the different hydration periods between the porous hydrogels and control. The calculated aggregate modulus, H(A), for the porous hydrogel reduced drastically from 10.99kPa in its non-hydrated state to about 0.001kPa after 7days' hydration, with the calculated shear modulus reducing from 30.92 to 0.14kPa, respectively. The porous PVA-NOCC hydrogel conformed to a biphasic, viscoelastic model, which has the desired properties required for any scaffold in cartilage tissue engineering.
    Matched MeSH terms: Extracellular Matrix/chemistry*
  5. Dashtdar H, Murali MR, Selvaratnam L, Balaji Raghavendran H, Suhaeb AM, Ahmad TS, et al.
    PeerJ, 2016;4:e1650.
    PMID: 26966647 DOI: 10.7717/peerj.1650
    Chondrogenic differentiation of mesenchymal stromal cells (MSCs) in the form of pellet culture and encapsulation in alginate beads has been widely used as conventional model for in vitro chondrogenesis. However, comparative characterization between differentiation, hypertrophic markers, cell adhesion molecule and ultrastructural changes during alginate and pellet culture has not been described. Hence, the present study was conducted comparing MSCs cultured in pellet and alginate beads with monolayer culture. qPCR was performed to assess the expression of chondrogenic, hypertrophic, and cell adhesion molecule genes, whereas transmission electron microscopy (TEM) was used to assess the ultrastructural changes. In addition, immunocytochemistry for Collagen type II and aggrecan and glycosaminoglycan (GAG) analysis were performed. Our results indicate that pellet and alginate bead cultures were necessary for chondrogenic differentiation of MSC. It also indicates that cultures using alginate bead demonstrated significantly higher (p < 0.05) chondrogenic but lower hypertrophic (p < 0.05) gene expressions as compared with pellet cultures. N-cadherin and N-CAM1 expression were up-regulated in second and third weeks of culture and were comparable between the alginate bead and pellet culture groups, respectively. TEM images demonstrated ultrastructural changes resembling cell death in pellet cultures. Our results indicate that using alginate beads, MSCs express higher chondrogenic but lower hypertrophic gene expression. Enhanced production of extracellular matrix and cell adhesion molecules was also observed in this group. These findings suggest that alginate bead culture may serve as a superior chondrogenic model, whereas pellet culture is more appropriate as a hypertrophic model of chondrogenesis.
    Matched MeSH terms: Extracellular Matrix
  6. Papadaki V, Asada K, Watson JK, Tamura T, Leung A, Hopkins J, et al.
    Cancers (Basel), 2020 Nov 13;12(11).
    PMID: 33202923 DOI: 10.3390/cancers12113362
    Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-β and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer.
    Matched MeSH terms: Extracellular Matrix Proteins
  7. Chong PP, Chin VK, Wong WF, Madhavan P, Yong VC, Looi CY
    Genes (Basel), 2018 Nov 07;9(11).
    PMID: 30405082 DOI: 10.3390/genes9110540
    Candida albicans is an opportunistic fungal pathogen, which causes a plethora of superficial, as well as invasive, infections in humans. The ability of this fungus in switching from commensalism to active infection is attributed to its many virulence traits. Biofilm formation is a key process, which allows the fungus to adhere to and proliferate on medically implanted devices as well as host tissue and cause serious life-threatening infections. Biofilms are complex communities of filamentous and yeast cells surrounded by an extracellular matrix that confers an enhanced degree of resistance to antifungal drugs. Moreover, the extensive plasticity of the C. albicans genome has given this versatile fungus the added advantage of microevolution and adaptation to thrive within the unique environmental niches within the host. To combat these challenges in dealing with C. albicans infections, it is imperative that we target specifically the molecular pathways involved in biofilm formation as well as drug resistance. With the advent of the -omics era and whole genome sequencing platforms, novel pathways and genes involved in the pathogenesis of the fungus have been unraveled. Researchers have used a myriad of strategies including transcriptome analysis for C. albicans cells grown in different environments, whole genome sequencing of different strains, functional genomics approaches to identify critical regulatory genes, as well as comparative genomics analysis between C. albicans and its closely related, much less virulent relative, C. dubliniensis, in the quest to increase our understanding of the mechanisms underlying the success of C. albicans as a major fungal pathogen. This review attempts to summarize the most recent advancements in the field of biofilm and antifungal resistance research and offers suggestions for future directions in therapeutics development.
    Matched MeSH terms: Extracellular Matrix
  8. Agarwal P, Agarwal R
    Expert Opin Ther Targets, 2018 07;22(7):629-638.
    PMID: 29883239 DOI: 10.1080/14728222.2018.1486822
    INTRODUCTION: Disturbances of extracellular matrix (ECM) homeostasis in trabecular meshwork (TM) cause increased aqueous outflow resistance leading to elevated intraocular pressure (IOP) in glaucomatous eyes. Therefore, restoration of ECM homeostasis is a rational approach to prevent disease progression. Since renin-angiotensin system (RAS) inhibition positively alters ECM homeostasis in cardiovascular pathologies involving pressure and volume overload, it is likely that RAS inhibitors reduce IOP primarily by restoring ECM homeostasis. Areas covered: Current evidence showing the presence of RAS components in ocular tissue and its role in regulating aqueous humor dynamics is briefly summarized. The role of RAS in ECM remodeling is discussed both in terms of its effects on ECM synthesis and its breakdown. The mechanisms of ECM remodeling involving interactions of RAS with transforming growth factor-β, Wnt/β-catenin signaling, bone morphogenic proteins, connective tissue growth factor, and matrix metalloproteinases in ocular tissue are discussed. Expert opinion: Current literature strongly indicates a significant role of RAS in ECM remodeling in TM of hypertensive eyes. Hence, IOP-lowering effect of RAS inhibitors may primarily be attributed to restoration of ECM homeostasis in aqueous outflow pathways rather than its vascular effects. However, the mechanistic targets for RAS inhibitors have much wider distribution and consequences, which remain relatively unexplored in TM.
    Matched MeSH terms: Extracellular Matrix/drug effects*; Extracellular Matrix/metabolism
  9. Ayele T, Zuki AB, Noorjahan BM, Noordin MM
    J Mater Sci Mater Med, 2010 May;21(5):1721-30.
    PMID: 20135201 DOI: 10.1007/s10856-010-4007-7
    The aim of this study was to engineer skeletal muscle tissue for repair abdominal wall defects. Myoblast were seeded onto the scaffolds and cultivated in vitro for 5 days. Full thickness abdominal wall defects (3 x 4 cm) were created in 18 male New Zealand white rabbits and randomly divided into two equal groups. The defects of the first group were repaired with myoblast-seeded-bovine tunica vaginalis whereas the second group repaired with non-seeded-bovine tunica vaginalis and function as a control. Three animals were sacrificed at 7th, 14th, and 30th days of post-implantation from each group and the explanted specimens were subjected to macroscopic and microscopic analysis. In every case, seeded scaffolds have better deposition of newly formed collagen with neo-vascularisation than control group. Interestingly, multinucleated myotubes and myofibers were only detected in cell-seeded group. This study demonstrated that myoblast-seeded-bovine tunica vaginalis can be used as an effective scaffold to repair severe and large abdominal wall defects with regeneration of skeletal muscle tissue.
    Matched MeSH terms: Extracellular Matrix
  10. Rothan HA, Djordjevic I, Bahrani H, Paydar M, Ibrahim F, Abd Rahmanh N, et al.
    Int J Med Sci, 2014;11(10):1029-38.
    PMID: 25136258 DOI: 10.7150/ijms.8895
    Platelet rich plasma clot- releasate (PRCR) shows significant influence on tissue regeneration in clinical trials. Although, the mechanism of PRCR effect on fibroblast differentiation has been studied on 2D culture system, a detailed investigation is needed to establish the role of PRCR in cell seeded in 3D scaffolds. Therefore, a study was conducted to evaluate the influence of PRCR in fibroblasts (DFB) differentiation and extracellular matrix formation on both 3D and 2D culture systems. Cell viability was measured using MTT assay and DFB differentiation was evaluated by determining the expression levels of nucleostamin and alpha smooth muscle actin (α-SMA), using indirect immunostaining and Western blotting. The expression levels of extracellular matrix genes (collagen-I, collagen-III, fibronectin and laminin) and focal adhesion formation gene (integrin beta-1) were measured using Real-time PCR. The PRCR at 10% showed significant effect on cells viability compared with 5% and 20% in both culture environments. The decrease in the expression levels of nucleostamin and the increase in α-SMA signify the DFB differentiation to myofibroblast-like cells that was prominently greater in 3D compared to 2D culture. In 3D culture systems, the total collage production, expression levels of the extracellular matrix gene and the focal adhesion gene were increased significantly compared to 2D culture. In conclusion, 3D culture environments enhances the proliferative and differentiation effects of PRCR on DFB, thereby potentially increases the efficacy of DFB for future tissue engineering clinical application.
    Matched MeSH terms: Extracellular Matrix/metabolism*
  11. Lee, Soo Leng, Zainal Ariff Abdul Rahman, Tsujigiwa, Hidetsugu, Takabatake, Kiyofumi, Nakano, Keisuke, Chai, Wen Lin, et al.
    Ann Dent, 2016;23(1):13-22.
    MyJurnal
    In recent years, three-dimensional (3D) in vitro cell culture models have earned great attention, especially in the field of human cancer disease modelling research as they provide a promising alternative towards the conventional two-dimensional (2D) monolayer culture of cells with improved tissue organization. In 2D cell culture systems, the complexity of cells on a planar surface does not accurately reflects the in vivo cellular microenvironment. Cells propagated in 3D cell culture model, on the other hand, exhibit physiologically relevant cell-to-cell interactions and cell-to-extracellular matrix (ECM) interactions, important in maintaining a normal homeostasis and specificity of tissues. This review gives an overview on 2D models and their limitations, followed by 3D cell culture models, their advantages, drawbacks and challenges in present perspectives. The review also highlights the dissimilarities of 2D and 3D models and the applicability of 3D models in current cancer research
    Matched MeSH terms: Extracellular Matrix
  12. Baie SH, Sheikh KA
    J Ethnopharmacol, 2000 Nov;73(1-2):15-30.
    PMID: 11025135
    Haruan has been proved to influence the different phases of wound healing process. The current research focuses on the effects of haruan on the different constituents of extracellular matrix of healing wounds in normal and diabetic rats. Anaesthetized normal and streptozotocin induced diabetic rats were provided with excision wounds at the back and then animals were divided into four groups as: group 1, wounds treated with cetrimide+haruan cream; group 2, wounds treated with haruan cream; group 3, wounds treated with cetrimide (commercial) cream; and group 4, wounds untreated and served as control. Animals were sacrificed after 3, 6, 9 and 12 days. These wounds were used to determine the hexosamine, protein, uronic acid and glycosaminoglycan contents and the wound contraction. The results suggested a marked increase (P<0.05) in the uronic acid, hexosamine and dermatan sulfate contents on day 3 of group 1 when compared with groups 2-4. Wound contraction of group 1 was also markedly enhanced of group 1 (P<0.01) when compared with groups 2- 4. On the basis of these results, we conclude that haruan enhances the synthesis of different glycosaminoglycans in healing wounds, which are the first component of extracellular matrix to be synthesized during the wound healing process. The enhanced levels of glycosaminoglycans may help in the formation of a resistant scar and enhanced wound contraction represents the positive influence of haruan on the fibroplastic phase of wound healing.
    Matched MeSH terms: Extracellular Matrix/metabolism*
  13. Azhim A, Syazwani N, Morimoto Y, Furukawa KS, Ushida T
    J Biomater Appl, 2014 Jul;29(1):130-41.
    PMID: 24384523 DOI: 10.1177/0885328213517579
    A novel decellularization method using sonication treatment is described. Sonication treatment is the combination of physical and chemical agents. These methods will disrupt cell membrane and release cell contents to external environments. The cell removal was facilitated by subsequent rinsing of sodium dodecyl sulfate detergents. Sonication treatment is used in the preparation of complete decellularized bioscaffolds. The aim of this study is to confirm the usefulness of sonication treatment for preparation of biological scaffolds. In this study, samples of aortic tissues are decellularized by sonication treatment at frequency of 170 kHz in 0.1% and 2% sodium dodecyl sulfate detergents for 10-h treatment time. The relation between decellularization and sonication parameters such as dissolved oxygen concentration, conductivity, and pH is investigated. Histological analysis and biomechanical testing is performed to evaluate cell removal efficiency as well as changes in biomechanical properties. Minimal inflammation response elicit by bioscaffolds is confirmed by xenogeneic implantation and immunohistochemistry. Sonication treatment is able to produce complete decellularized tissue suggesting that these treatments could be applied widely as one of the decellularization method.
    Matched MeSH terms: Extracellular Matrix/chemistry
  14. Munirah S, Kim SH, Ruszymah BH, Khang G
    Eur Cell Mater, 2008 Feb 21;15:41-52.
    PMID: 18288632
    Our preliminary results indicated that fibrin and poly(lactic-co-glycolic acid) (PLGA) hybrid scaffold promoted early chondrogenesis of articular cartilage constructs in vitro. The aim of this study was to evaluate in vivo cartilaginous tissue formation by chondrocyte-seeded fibrin/PLGA hybrid scaffolds. PLGA scaffolds were soaked carefully, in chondrocyte-fibrin suspension, and polymerized by dropping thrombin-calcium chloride (CaCl2) solution. PLGA-seeded chondrocytes were used as a control. Resulting constructs were implanted subcutaneously, at the dorsum of nude mice, for 4 weeks. Macroscopic observation, histological evaluation, gene expression and sulphated-glycosaminoglycan (sGAG) analyses were performed at each time point of 1, 2 and 4 weeks post-implantation. Cartilaginous tissue formation in fibrin/PLGA hybrid construct was confirmed by the presence of lacunae and cartilage-isolated cells embedded within basophilic ground substance. Presence of proteoglycan and glycosaminoglycan (GAG) in fibrin/PLGA hybrid constructs was confirmed by positive Safranin O and Alcian Blue staining. Collagen type II exhibited intense immunopositivity at the pericellular matrices. Chondrogenic properties were further demonstrated by the expression of gene encoded cartilage-specific markers, collagen type II and aggrecan core protein. The sGAG production in fibrin/PLGA hybrid constructs was higher than in the PLGA group. In conclusion, fibrin/PLGA hybrid scaffold promotes cartilaginous tissue formation in vivo and may serve as a potential cell delivery vehicle and a structural basis for articular cartilage tissue-engineering.
    Matched MeSH terms: Extracellular Matrix/metabolism
  15. Naidu M
    Malays J Med Sci, 2009 Apr;16(2):10-4.
    PMID: 22589652 MyJurnal
    Wallerian degeneration is a complicated process whereby axons and myelin sheaths undergo degeneration, and eventually are phagocytosed by macrophages and Schwann cells following nerve damage. Schwann cells proliferate and the endoneural tubes persist. In addition, neurotrophins, neural cell adhesion molecules, cytokines and other soluble factors are upregulated to facilitate regeneration. The important role of cellular components, neurotrophins, and extracellular matrix components, including cell surface molecules involved in this regenerative process, is highlighted and discussed in this review.
    Matched MeSH terms: Extracellular Matrix
  16. Mansouri N, SamiraBagheri
    Mater Sci Eng C Mater Biol Appl, 2016 Apr 1;61:906-21.
    PMID: 26838922 DOI: 10.1016/j.msec.2015.12.094
    The actual in vivo tissue scaffold offers a three-dimensional (3D) structural support along with a nano-textured surfaces consist of a fibrous network in order to deliver cell adhesion and signaling. A scaffold is required, until the tissue is entirely regenerated or restored, to act as a temporary ingrowth template for cell proliferation and extracellular matrix (ECM) deposition. This review depicts some of the most significant three dimensional structure materials used as scaffolds in various tissue engineering application fields currently being employed to mimic in vivo features. Accordingly, some of the researchers' attempts have envisioned utilizing graphene for the fabrication of porous and flexible 3D scaffolds. The main focus of this paper is to evaluate the topographical and topological optimization of scaffolds for tissue engineering applications in order to improve scaffolds' mechanical performances.
    Matched MeSH terms: Extracellular Matrix/metabolism; Extracellular Matrix/chemistry
  17. Ab-Rahim S, Selvaratnam L, Kamarul T
    Cell Biol Int, 2008 Jul;32(7):841-7.
    PMID: 18479947 DOI: 10.1016/j.cellbi.2008.03.016
    Articular cartilage extracellular matrix (ECM) plays a crucial role in regulating chondrocyte functions via cell-matrix interaction, cytoskeletal organization and integrin-mediated signaling. Factors such as interleukins, basic fibroblast growth factor (bFGF), bone morphogenic proteins (BMPs) and insulin-like growth factor (IGF) have been shown to modulate the synthesis of extracellular matrix in vitro. However, the effects of TGF-beta1 and beta-estradiol in ECM regulation require further investigation, although there have been suggestions that these factors do play a positive role. To establish the role of these factors on chondrocytes derived from articular joints, a study was conducted to investigate the effects of TGF-beta1 and beta-estradiol on glycosaminoglycan secretion and type II collagen distribution (two major component of cartilage ECM in vivo). Thus, chondrocyte cultures initiated from rabbit articular cartilage were treated with 10ng/ml of TGF-beta1, 10nM of beta-estradiol or with a combination of both factors. Sulphated glycosaminoglycan (GAG) and type II collagen levels were then measured in both these culture systems. The results revealed that the synthesis of GAG and type II collagen was shown to be enhanced in the TGF-beta1 treated cultures. This increase was also noted when TGF-beta1 and beta-estradiol were both used as culture supplements. However, beta-estradiol alone did not appear to affect GAG or type II collagen deposition. There was also no difference between the amount of collagen type II and GAG being expressed when chondrocyte cultures were treated with TGF-beta1 when compared with cultures treated with combined factors. From this, we conclude that although TGF-beta1 appears to stimulate chondrocyte ECM synthesis, beta-estradiol fails to produce similar effects. The findings of this study confirm that contrary to previous claims, beta-estradiol has little or no effect on chondrocyte ECM synthesis. Furthermore, the use of TGF-beta1 may be useful in future studies looking into biological mechanisms by which ECM synthesis in chondrocyte cultures can be augmented, particularly for clinical application.
    Matched MeSH terms: Extracellular Matrix/drug effects; Extracellular Matrix/metabolism*
  18. Zakaria MA, Rajab NF, Chua EW, Selvarajah GT, Masre SF
    Cancer Invest, 2020 Sep;38(8-9):445-462.
    PMID: 32713210 DOI: 10.1080/07357907.2020.1802474
    Tissues become more rigid during tumorigenesis and have been identified as a driving factor for tumor growth. Here, we highlight the concept of tissue rigidity, contributing factors that increase tissue rigidity, and mechanisms that promote tumor growth initiated by increased tissue rigidity. Various factors lead to increased tissue rigidity, promoting tumor growth by activating focal adhesion kinase (FAK) and Rho-associated kinase (ROCK). Consequently, result in recruitment of cancer-associated fibroblasts (CAFs), epithelial-mesenchymal transition (EMT) and tumor protection from immunosurveillance. We also discussed the rationale for targeting tumor tissue rigidity and its potential for cancer treatment.
    Matched MeSH terms: Extracellular Matrix/pathology
  19. Morris MA, Dawson CW, Laverick L, Davis AM, Dudman JP, Raveenthiraraj S, et al.
    Sci Rep, 2016;6:19533.
    PMID: 26782058 DOI: 10.1038/srep19533
    Approximately 20% of global cancer incidence is causally linked to an infectious agent. Epstein-Barr virus (EBV) accounts for around 1% of all virus-associated cancers and is associated with nasopharyngeal carcinoma (NPC). Latent membrane protein 1 (LMP1), the major oncoprotein encoded by EBV, behaves as a constitutively active tumour necrosis factor (TNF) receptor activating a variety of signalling pathways, including the three classic MAPKs (ERK-MAPK, p38 MAPK and JNK/SAPK). The present study identifies novel signalling properties for this integral membrane protein via the induction and secretion of activin A and TGFβ1, which are both required for LMP1's ability to induce the expression of the extracellular matrix protein, fibronectin. However, it is evident that LMP1 is unable to activate the classic Smad-dependent TGFβ signalling pathway, but rather elicits its effects through the non-Smad arm of TGFβ signalling. In addition, there is a requirement for JNK/SAPK signalling in LMP1-mediated fibronectin induction. LMP1 also induces the expression and activation of the major fibronectin receptor, α5β1 integrin, an effect that is accompanied by increased focal adhesion formation and turnover. Taken together, these findings support the putative role for LMP1 in the pathogenesis of NPC by contributing to the metastatic potential of epithelial cells.
    Matched MeSH terms: Extracellular Matrix Proteins
  20. Agarwal R, Agarwal P
    Exp Biol Med (Maywood), 2017 Feb;242(4):374-383.
    PMID: 27798117 DOI: 10.1177/1535370216675065
    Disturbances of extracellular matrix homeostasis are associated with a number of pathological conditions. The ability of extracellular matrix to provide contextual information and hence control the individual or collective cellular behavior is increasingly being recognized. Hence, newer therapeutic approaches targeting extracellular matrix remodeling are widely investigated. We reviewed the current literature showing the effects of resveratrol on various aspects of extracellular matrix remodeling. This review presents a summary of the effects of resveratrol on extracellular matrix deposition and breakdown. Mechanisms of action of resveratrol in extracellular matrix deposition involving growth factors and their signaling pathways are discussed. Involvement of phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways and role of transcription factors and sirtuins on the effects of resveratrol on extracellular matrix homeostasis are summarized. It is evident from the literature presented in this review that resveratrol has significant effects on both the synthesis and breakdown of extracellular matrix. The major molecular targets of the action of resveratrol are growth factors and their signaling pathways, phosphoinositol-3-kinase/Akt and mitogen-activated protein kinase pathways, transcription factors, and SIRT-1. The effects of resveratrol on extracellular matrix and the molecular targets appear to be related to experimental models, experimental environment as well as the doses.
    Matched MeSH terms: Extracellular Matrix/pathology*
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