Tendon response to matrix unloading is determined by the patho-physiological niche.
edeker JG Abstract Although the molecular mechanisms behind tendon disease remain obscure, aberrant stromal matrix turnover and tissue hypervascularity are known hallmarks of advanced tendinopathy. We harness a tendon explant model to unwind complex cross-talk between the stromal and vascular tissue compartments. We identify the hypervascular tendon niche as a state-switch that gates degenerative matrix remodeling within the tissue stroma. Here pathological conditions resembling hypervascular tendon disease provoke rapid cell-mediated tissue breakdown upon mechanical unloading, in contrast to unloaded tendons that...
Source: Matrix Biology - January 6, 2020 Category: Molecular Biology Authors: Wunderli SL, Blache U, Piccoli AB, Niederöst B, Holenstein CN, Passini FS, Silván U, Bundgaard L, Keller UAD, Snedeker JG Tags: Matrix Biol Source Type: research

Single cell RNA-sequencing reveals cellular heterogeneity and trajectories of lineage specification during murine embryonic limb development.
Abstract The coordinated spatial and temporal regulation of gene expression in the murine hindlimb determines the identity of mesenchymal progenitors and the development of diversity of musculoskeletal tissues they form. Hindlimb development has historically been studied with lineage tracing of individual genes selected a priori, or at the bulk tissue level, which does not allow for the determination of single cell transcriptional programs yielding mature cell types and tissues. To identify the cellular trajectories of lineage specification during limb bud development, we used single cell mRNA sequencing (scRNA-se...
Source: Matrix Biology - December 21, 2019 Category: Molecular Biology Authors: Kelly NH, Huynh NPT, Guilak F Tags: Matrix Biol Source Type: research

Hypomorphic zebrafish models mimic the musculoskeletal phenotype of β4GalT7-deficient Ehlers-Danlos syndrome.
In conclusion, we generated the first viable animal models for spEDS-B4GALT7, and show that in early development the human spEDS-B4GALT7 phenotype is faithfully mimicked in these zebrafish models. Our findings underscore a key role for β4GalT7 in early development of cartilage, bone and muscle. These models will lead to a better understanding of spEDS-B4GALT7 and can be used in future efforts focusing on therapeutic applications. PMID: 31862401 [PubMed - as supplied by publisher] (Source: Matrix Biology)
Source: Matrix Biology - December 17, 2019 Category: Molecular Biology Authors: Delbaere S, Van Damme T, Syx D, Symoens S, Coucke P, Willaert A, Malfait F Tags: Matrix Biol Source Type: research

Loss of LRP1 promotes acquisition of contractile-myofibroblast phenotype and release of active TGF- β1 from ECM stores.
Loss of LRP1 promotes acquisition of contractile-myofibroblast phenotype and release of active TGF-β1 from ECM stores. Matrix Biol. 2019 Dec 10;: Authors: Schnieder J, Mamazhakypov A, Birnhuber A, Wilhelm J, Kwapiszewska G, Ruppert C, Markart P, Wujak L, Rubio K, Barreto G, Schaefer L, Wygrecka M Abstract In healing tissue, fibroblasts differentiate to α-smooth muscle actin (SMA)-expressing contractile-myofibroblasts, which pull the wound edges together ensuring proper tissue repair. Uncontrolled expansion of the myofibroblast population may, however, lead to excessive tissue scarring and f...
Source: Matrix Biology - December 10, 2019 Category: Molecular Biology Authors: Schnieder J, Mamazhakypov A, Birnhuber A, Wilhelm J, Kwapiszewska G, Ruppert C, Markart P, Wujak L, Rubio K, Barreto G, Schaefer L, Wygrecka M Tags: Matrix Biol Source Type: research

Heparanase promotes myeloma stemness and in vivo tumorigenesis.
Abstract Heparanase is known to enhance the progression of many cancer types and is associated with poor patient prognosis. We recently reported that after patients with multiple myeloma were treated with high dose chemotherapy, the tumor cells that emerged upon relapse expressed a much higher level of heparanase than was present prior to therapy. Because tumor cells having stemness properties are thought to seed tumor relapse, we investigated whether heparanase had a role in promoting myeloma stemness. When plated at low density and grown in serum-free conditions that support survival and expansion of stem-like c...
Source: Matrix Biology - December 5, 2019 Category: Molecular Biology Authors: Tripathi K, Ramani VC, Bandari SK, Amin R, Brown EE, Ritchie JP, Stewart MD, Sanderson RD Tags: Matrix Biol Source Type: research

The role of extracellular matrix in biomechanics and its impact on bioengineering of cells and 3D tissues.
Abstract The cells and tissues of the human body are constantly exposed to exogenous and endogenous forces that are referred to as biomechanical cues. They guide and impact cellular processes and cell fate decisions on the nano-, micro- and macro-scale, and are therefore critical for normal tissue development and maintaining tissue homeostasis. Alterations in the extracellular matrix composition of a tissue combined with abnormal mechanosensing and mechanotransduction can aberrantly activate signaling pathways that promote disease development. Such processes are therefore highly relevant for disease modelling or w...
Source: Matrix Biology - December 2, 2019 Category: Molecular Biology Authors: Urbanczyk M, Layland SL, Schenke-Layland K Tags: Matrix Biol Source Type: research

Scavenger Receptor Cysteine-Rich domains of Lysyl Oxidase-Like2 regulate endothelial ECM and angiogenesis through non-catalytic scaffolding mechanisms.
Abstract Lysyl oxidases are major actors of microenvironment and extracellular matrix (ECM) remodeling. These cross-linking enzymes are thus involved in many aspects of physiopathology, including tumor progression, fibrosis and cardiovascular diseases. We have already shown that Lysyl Oxidase-Like 2 (LOXL2) regulates collagen IV deposition by endothelial cells and angiogenesis. We here provide evidence that LOXL2 also affects deposition of other ECM components, including fibronectin, thus altering structural and mechanical properties of the matrix generated by endothelial cells. LOXL2 interacts intracellularly and...
Source: Matrix Biology - November 20, 2019 Category: Molecular Biology Authors: Umana-Diaz C, Pichol-Thievend C, Marchand MF, Atlas Y, Salza R, Malbouyres M, Barret A, Teillon J, Ardidie-Robouant C, Ruggiero F, Monnot C, Girard P, Guilluy C, Ricard-Blum S, Germain S, Muller L Tags: Matrix Biol Source Type: research

Glypican-6 stimulates intestinal elongation by simultaneously regulating Hedgehog and non-canonical Wnt signaling.
This study also provides experimental evidence that strongly suggests that GPC6 inhibits the activity of Wnt5a on the intestinal epithelium by binding to this growth factor, and reducing its release from the surrounding mesenchymal cells. Finally, we show that whereas the mesenchymal layer of GPC6-null intestines displays reduced cell proliferation and a thinner smooth muscle layer, epithelial cell differentiation is not altered in the mutant gut. PMID: 31756413 [PubMed - as supplied by publisher] (Source: Matrix Biology)
Source: Matrix Biology - November 19, 2019 Category: Molecular Biology Authors: Shi W, Kaneiwa T, Cydzik M, Gariepy J, Filmus J Tags: Matrix Biol Source Type: research

A novel ADAMTS17 variant that causes Weill-Marchesani syndrome 4 alters fibrillin-1 and collagen type I deposition in the extracellular matrix.
Abstract Weill-Marchesani syndrome (WMS) is a rare genetic disorder that affects the musculoskeletal system, the eye, and the cardiovascular system. Individuals with WMS present with short stature, joint contractures, thick skin, microspherophakia, small and dislocated lenses, and cardiac valve anomalies. WMS can be caused by recessive mutations in ADAMTS10 (WMS 1), ADAMTS17 (WMS 4), or LTBP2 (WMS 3), or by dominant mutations in fibrillin-1 (FBN1) (WMS 2); all genes encode secreted extracellular matrix (ECM) proteins. Individuals with WMS 4 due to ADAMTS17 mutations appear to have less severe cardiac involvement a...
Source: Matrix Biology - November 11, 2019 Category: Molecular Biology Authors: Karoulias SZ, Beyens A, Balic Z, Symoens S, Vandersteen A, Rideout AL, Dickinson J, Callewaert B, Hubmacher D Tags: Matrix Biol Source Type: research

TonEBP-deficiency accelerates intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression.
Abstract The tonicity-responsive enhancer binding protein (TonEBP) plays an important role in intervertebral disc and axial skeleton embryogenesis. However, the contribution of this osmoregulatory transcription factor in postnatal intervertebral disc homeostasis is not known in vivo. Here, we show for the first time that TonEBP-deficient mice have pronounced age-related degeneration of the intervertebral disc with annular and endplate herniations. Using FTIR-imaging spectroscopy, quantitative immunohistochemistry, and tissue-specific transcriptomic analysis, we provide morphological and molecular evidence that the...
Source: Matrix Biology - November 7, 2019 Category: Molecular Biology Authors: Tessier S, Tran VA, Ottone OK, Novais EJ, Doolittle A, DiMuzio MJ, Shapiro IM, Risbud MV Tags: Matrix Biol Source Type: research

Accumulation of versican facilitates wound healing: implication of its initial ADAMTS-cleavage site.
Abstract Versican is a large chondroitin sulfate/dermatan sulfate proteoglycan in the extracellular matrix, and is expressed at high levels in tissues during development and remodeling in pathological conditions. Its core protein is cleaved at a region close to the N-terminal end of CSβ domain by several members of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, i.e., ADAMTS-1, 4, 5, 9, 15, and 20. Here, using a CRISPR/Cas9 system, we generated knock-in mice (V1R), which express an ADAMTS cleavage-resistant versican. Some V1R homozygote mice, termed R/R, exhibit syndactyly and ...
Source: Matrix Biology - October 26, 2019 Category: Molecular Biology Authors: Islam S, Chuensirikulchai K, Khummuang S, Keratibumrungpong T, Kongtawelert P, Kasinrerk W, Hatano S, Nagamachi A, Honda H, Watanabe H Tags: Matrix Biol Source Type: research

Bipartite mechanism for laminin-integrin interactions: identification of the integrin-binding site in LG domains of the laminin α chain.
Bipartite mechanism for laminin-integrin interactions: identification of the integrin-binding site in LG domains of the laminin α chain. Matrix Biol. 2019 Oct 24;: Authors: Taniguchi Y, Takizawa M, Li S, Sekiguchi K Abstract Laminins are major cell-adhesive proteins consisting of α, β, and γ chains, in which the three C-terminal globular domains of the α chain (LMα/LG1-3) and the C-terminal tail region of the γ1 chain (LMγ1-tail) are required for binding to integrin. Despite the recent progress on the role of LMγ1-tail in coordinating the metal ion-...
Source: Matrix Biology - October 24, 2019 Category: Molecular Biology Authors: Taniguchi Y, Takizawa M, Li S, Sekiguchi K Tags: Matrix Biol Source Type: research

Role of hypoxia in skeletal muscle fibrosis: Synergism between hypoxia and TGF- β signaling upregulates CCN2/CTGF expression specifically in muscle fibers.
Role of hypoxia in skeletal muscle fibrosis: Synergism between hypoxia and TGF-β signaling upregulates CCN2/CTGF expression specifically in muscle fibers. Matrix Biol. 2019 Oct 24;: Authors: Valle-Tenney R, Rebolledo D, Lipson KE, Brandan E Abstract Several skeletal muscle diseases are characterized by fibrosis, the excessive accumulation of extracellular matrix. Transforming growth factor-β (TGF-β) and connective tissue growth factor (CCN2/CTGF) are two profibrotic factors augmented in fibrotic skeletal muscle, together with signs of reduced vasculature that implies a decrease in oxyge...
Source: Matrix Biology - October 24, 2019 Category: Molecular Biology Authors: Valle-Tenney R, Rebolledo D, Lipson KE, Brandan E Tags: Matrix Biol Source Type: research

Elastic Fiber Ultrastructure and Assembly.
Abstract Studies over the years have described a filamentous structure to mature elastin that suggests a complicated packing arrangement of tropoelastin subunits. The currently accepted mechanism for tropoelastin assembly requires microfibrils to serve as a physical extracellular scaffold for alignment of tropoelastin monomers during and before crosslinking. However, recent evidence suggests that the initial stages of tropoelastin assembly occur within the cell or at unique assembly sites on the plasma membrane where tropoelastin self assembles to form elastin aggregates. Outside the cell, elastin aggregates trans...
Source: Matrix Biology - October 24, 2019 Category: Molecular Biology Authors: Kozel BA, Mecham RP Tags: Matrix Biol Source Type: research

A tribute to Ladislas Robert.
Abstract This Thematic Minireview Series of Matrix Biology focused on elastin, from structure to disease celebrates the memory of Ladislas Robert, a pioneer in Matrix Biology in France and Europe. Since his first publication on elastin and elastases in 1957, the huge development in matrix biology led to major findings on elastic fibers and their component proteins including elastin architecture, the role of fibrillins and microfibril-binding proteins on elastin assembly, the effects of sequence variants of human tropoelastin on its assembly, structure and functions, the role of elastin peptides in health and disea...
Source: Matrix Biology - October 24, 2019 Category: Molecular Biology Authors: Jacob MP, Ricard-Blum S Tags: Matrix Biol Source Type: research

H-Ras activation and fibroblast-induced TGF- β signaling promote laminin-332 accumulation and invasion in cutaneous squamous cell carcinoma.
In conclusion, we demonstrate the presence of laminin-332 in the invasive front of cSCC tumors and report a new Ras/TGF-β-dependent mechanism that promotes laminin-332 accumulation and cancer cell invasion. PMID: 31655292 [PubMed - as supplied by publisher] (Source: Matrix Biology)
Source: Matrix Biology - October 24, 2019 Category: Molecular Biology Authors: Siljamäki E, Rappu P, Riihilä P, Nissinen L, Kähäri VM, Heino J Tags: Matrix Biol Source Type: research

Type III Collagen is a Key Regulator of the Collagen Fibrillar Structure and Biomechanics of Articular Cartilage and Meniscus.
This study queried the role of type III collagen in the structure and biomechanical functions of two structurally distinctive tissues in the knee joint, type II collagen-rich articular cartilage and type I collagen-dominated meniscus. Integrating outcomes from atomic force microscopy-based nanomechanical tests, collagen fibril nanostructural analysis, collagen cross-linking analysis and histology, we elucidated the impact of type III collagen haplodeficiency on the morphology, nanostructure and biomechanical properties of articular cartilage and meniscus in Col3a1+/- mice. Reduction of type III collagen leads to increased ...
Source: Matrix Biology - October 23, 2019 Category: Molecular Biology Authors: Wang C, Brisson BK, Terajima M, Li Q, Hoxha K, Han B, Goldberg AM, Sherry Liu X, Marcolongo MS, Enomoto-Iwamoto M, Yamauchi M, Volk SW, Han L Tags: Matrix Biol Source Type: research

Rise and fall of elastic fibers from development to aging. Consequences on arterial structure-function and therapeutical perspectives.
cob MP, Faury G Abstract In the arteries of vertebrates, evolution has given rise to resilient macromolecular structures, elastin and elastic fibers, capable of sustaining an elevated blood pressure and smoothing the discontinuous blood flow and pressure generated by the heart. Elastic fibers are produced only during development and childhood, before being progressively degraded by mechanical stress and enzymatic activities during adulthood and aging. During this period, arterial elastic fiber calcification and loading of lipids also occur, all of these events conducting to arteriosclerosis. This leads to a progre...
Source: Matrix Biology - September 4, 2019 Category: Molecular Biology Authors: Fhayli W, Boëté Q, Harki O, Briançon-Marjollet A, Jacob MP, Faury G Tags: Matrix Biol Source Type: research

Abrogation of EMILIN1- β1 integrin interaction promotes experimental colitis and colon carcinogenesis.
Abrogation of EMILIN1-β1 integrin interaction promotes experimental colitis and colon carcinogenesis. Matrix Biol. 2019 Aug 31;: Authors: Capuano A, Pivetta E, Sartori G, Bosisio G, Favero A, Cover E, Andreuzzi E, Colombatti A, Cannizzaro R, Scanziani E, Minoli L, Bucciotti F, Lopez AIA, Gaspardo K, Doliana R, Mongiat M, Spessotto P Abstract Colon cancer is one of the first tumor types where a functional link between inflammation and tumor onset has been described; however, the microenvironmental cues affecting colon cancer progression are poorly understood. Here we demonstrate that the expressio...
Source: Matrix Biology - August 31, 2019 Category: Molecular Biology Authors: Capuano A, Pivetta E, Sartori G, Bosisio G, Favero A, Cover E, Andreuzzi E, Colombatti A, Cannizzaro R, Scanziani E, Minoli L, Bucciotti F, Lopez AIA, Gaspardo K, Doliana R, Mongiat M, Spessotto P Tags: Matrix Biol Source Type: research

Circadian rhythms in skin and other elastic tissues.
Abstract Circadian rhythms are daily oscillations that, in mammals, are driven by both a master clock, located in the brain, and peripheral clocks in cells and tissues. Approximately 10% of the transcriptome, including extracellular matrix components, is estimated to be under circadian control. Whilst it has been established that certain collagens and extracellular matrix proteases are diurnally regulated (for example in tendon, cartilage and intervertebral disc) the role played by circadian rhythms in mediating elastic fiber homeostasis is poorly understood. Skin, arteries and lungs are dynamic, resilient, elasti...
Source: Matrix Biology - August 15, 2019 Category: Molecular Biology Authors: Sherratt MJ, Hopkinson L, Naven M, Hibbert SA, Ozols M, Eckersley A, Newton VL, Bell M, Meng QJ Tags: Matrix Biol Source Type: research

Multimerin-2 maintains vascular stability and permeability.
Abstract Multimerin-2 is an extracellular matrix glycoprotein and member of the elastin microfibril interface-located (EMILIN) family of proteins. Multimerin-2 is deposited along blood vessels and we previously demonstrated that it regulates the VEGFA/VEGFR2 signaling axis and angiogenesis. However, its role in modulating vascular homeostasis remains largely unexplored. Here we identified Multimerin-2 as a key molecule required to maintain vascular stability. RNAi knockdown of Multimerin-2 in endothelial cells led to cell-cell junctional instability and increased permeability. Mechanistically cell-cell junction di...
Source: Matrix Biology - August 15, 2019 Category: Molecular Biology Authors: Pellicani R, Poletto E, Andreuzzi E, Paulitti A, Doliana R, Bizzotto D, Braghetta P, Colladel R, Tarticchio G, Sabatelli P, Bucciotti F, Bressan G, Iozzo RV, Colombatti A, Bonaldo P, Mongiat M Tags: Matrix Biol Source Type: research

Disrupted type II collagenolysis impairs angiogenesis, delays endochondral ossification and initiates aberrant ossification in mouse limbs.
We report here that this mouse (Bailey) is viable. It has a significantly expanded growth plate and exhibits delayed and abnormal angiogenic invasion into the growth plate. Deeper electron microscopy analyses revealed that, at around five weeks of age, a small number of blood vessel(s) penetrate into the growth plate, leading to its abrupt shrinking and the formation of a bony bridge. Our results from in vitro and ex vivo studies suggest that collagen II matrikines stimulate the normal branching of endothelial cells and promote blood vessel invasion at the chondro-osseous junction. The results further suggest that failed c...
Source: Matrix Biology - August 2, 2019 Category: Molecular Biology Authors: Gauci SJ, Golub SB, Tatarczuch L, Lee E, Chan D, Walsh NC, Little CB, Stanton H, Lokmic Z, Sims NA, Mackie EJ, Fosang AJ Tags: Matrix Biol Source Type: research

Tendon tissue microdamage and the limits of intrinsic repair.
Abstract The transmission of mechanical muscle force to bone for musculoskeletal stability and movement is one of the most important functions of tendon. The load-bearing tendon core is composed of highly aligned collagen-rich fascicles interspersed with stromal cells (tenocytes). Despite being built to bear very high mechanical stresses, supra-physiological/repetitive mechanical overloading leads to tendon microdamage in fascicles, and potentially to tendon disease and rupture. To date, it is unclear to what extent intrinsic healing mechanisms of the tendon core compartment can repair microdamage. In the present ...
Source: Matrix Biology - July 17, 2019 Category: Molecular Biology Authors: Stauber T, Blache U, Snedeker JG Tags: Matrix Biol Source Type: research

Fibroblast activation protein restrains adipogenic differentiation and regulates matrix-mediated mTOR signaling.
te; E Abstract Obesity is a risk factor for multiple diseases, including diabetes, cardiovascular disease, and cancer. Within obese adipose tissue, multiple factors contribute to creating a disease-promoting environment, including metabolic dysfunction, inflammation, and fibrosis. Recent evidence points to fibrotic responses, particularly extracellular matrix remodeling, in playing a highly functional role in the pathogenesis of obesity. Fibroblast activation protein plays an essential role in remodeling collagen-rich matrices in the context of fibrosis and cancer. We observed that FAP-null mice have increased wei...
Source: Matrix Biology - July 17, 2019 Category: Molecular Biology Authors: Blomberg R, Beiting DP, Wabitsch M, Puré E Tags: Matrix Biol Source Type: research

Scaffold stiffness influences breast cancer cell invasion via EGFR-linked Mena upregulation and matrix remodeling.
Abstract Clinically, increased breast tumor stiffness is associated with metastasis and poorer outcomes. Yet, in vitro studies of tumor cells in 3D scaffolds have found decreased invasion in stiffer environments. To resolve this apparent contradiction, MDA-MB-231 breast tumor spheroids were embedded in 'low' (2 kPa) and 'high' (12 kPa) stiffness 3D hydrogels comprised of methacrylated gelatin/collagen I, a material that allows for physiologically-relevant changes in stiffness while matrix density is held constant. Cells in high stiffness materials exhibited delayed invasion, but more abundant actin-enriched pr...
Source: Matrix Biology - July 16, 2019 Category: Molecular Biology Authors: Berger AJ, Renner CM, Hale I, Yang X, Ponik SM, Weisman PS, Masters KS, Kreeger PK Tags: Matrix Biol Source Type: research

Biallelic KRT5 mutations in epidermolysis bullosa simplex, including a complete human keratin 5 "knock-out".
Biallelic KRT5 mutations in epidermolysis bullosa simplex, including a complete human keratin 5 "knock-out". Matrix Biol. 2019 Jul 11;: Authors: Vahidnezhad H, Youssefian L, Daneshpazhooh M, Mahmoudi H, Kariminejad A, Fischer J, Christiansen J, Schneider H, Guy A, Liu L, McGrath JA, Has C, Uitto J Abstract Epidermolysis bullosa simplex (EBS) is usually inherited as an autosomal dominant disease due to monoallelic gain-of-function mutations in KRT5 and KRT14. Although autosomal recessive forms of EBS have been associated with mutations in at least 10 genes, recessive EBS due to homozygous bia...
Source: Matrix Biology - July 11, 2019 Category: Molecular Biology Authors: Vahidnezhad H, Youssefian L, Daneshpazhooh M, Mahmoudi H, Kariminejad A, Fischer J, Christiansen J, Schneider H, Guy A, Liu L, McGrath JA, Has C, Uitto J Tags: Matrix Biol Source Type: research

Elastin architecture.
PMID: 31301399 [PubMed - as supplied by publisher] (Source: Matrix Biology)
Source: Matrix Biology - July 10, 2019 Category: Molecular Biology Authors: Vindin H, Mithieux SM, Weiss AS Tags: Matrix Biol Source Type: research

The role of elastin-derived peptides in human physiology and diseases.
Abstract Once considered as inert, the extracellular matrix recently revealed to be biologically active. Elastin is one of the most important components of the extracellular matrix. Many vital organs including arteries, lungs and skin contain high amounts of elastin to assure their correct function. Physiologically, the organism contains a determined quantity of elastin from the early development which may remain physiologically constant due to its very long half-life and very low turnover. Taking into consideration the continuously ongoing challenges during life, there is a physiological degradation of elastin in...
Source: Matrix Biology - July 8, 2019 Category: Molecular Biology Authors: Le Page A, Khalil A, Vermette P, Frost EH, Larbi A, Witkowski JM, Fulop T Tags: Matrix Biol Source Type: research

Peptide gels of fully-defined composition and mechanics for probing cell-cell and cell-matrix interactions in vitro.
y CLR Abstract Current materials used for in vitro 3D cell culture are often limited by their poor similarity to human tissue, batch-to-batch variability and complexity of composition and manufacture. Here, we present a "blank slate" culture environment based on a self-assembling peptide gel free from matrix motifs. The gel can be customised by incorporating matrix components selected to match the target tissue, with independent control of mechanical properties. Therefore the matrix components are restricted to those specifically added, or those synthesised by encapsulated cells. The flexible 3D culture ...
Source: Matrix Biology - July 8, 2019 Category: Molecular Biology Authors: Ashworth JC, Thompson JL, James JR, Slater CE, Pijuan-Galitó S, Lis-Slimak K, Holley RJ, Meade KA, Thompson A, Arkill KP, Tassieri M, Wright AJ, Farnie G, Merry CLR Tags: Matrix Biol Source Type: research

Tenascin-C increases lung metastasis by impacting blood vessel invasions.
stofori G, Mathelin C, Loustau T, Hussenet T, Orend G Abstract Metastasis is a major cause of death in cancer patients. The extracellular matrix molecule tenascin-C is a known promoter of metastasis, however the underlying mechanisms are not well understood. To further analyze the impact of tenascin-C on cancer progression we generated MMTV-NeuNT mice that develop spontaneous mammary tumors, on a tenascin-C knockout background. We also developed a syngeneic orthotopic model in which tumor cells derived from a MMTV-NeuNT tumor. Tumor cells were transfected with control shRNA or with shRNA to knockdown tenascin-C ex...
Source: Matrix Biology - July 6, 2019 Category: Molecular Biology Authors: Sun Z, Velázquez-Quesada I, Murdamoothoo D, Ahowesso C, Yilmaz A, Spenlé C, Averous G, Erne W, Oberndorfer F, Oszwald A, Kain R, Bourdon C, Mangin P, Deligne C, Midwood K, Abou-Faycal C, Lefebvre O, Klein A, van der Heyden M, Chenard MP, Christofori G, Tags: Matrix Biol Source Type: research

Trends in the design and use of elastin-like recombinamers as biomaterials.
e;guez-Cabello JC Abstract Elastin-like recombinamers (ELRs), which derive from one of the repetitive domains found in natural elastin, have been intensively studied in the last few years from several points of view. In this mini review, we discuss all the recent works related to the investigation of ELRs, starting with those that define these polypeptides as model intrinsically disordered proteins or regions (IDPs or IDRs) and its relevance for some biomedical applications. Furthermore, we summarize the current knowledge on the development of drug, vaccine and gene delivery systems based on ELRs, while also empha...
Source: Matrix Biology - July 6, 2019 Category: Molecular Biology Authors: Ibáñez-Fonseca A, Flora T, Acosta S, Rodríguez-Cabello JC Tags: Matrix Biol Source Type: research

Sequence variants of human tropoelastin affecting assembly, structural characteristics and functional properties of polymeric elastin in health and disease.
Abstract Elastin is the polymeric protein responsible for the physiologically important properties of extensibility and elastic recoil of cardiovascular, pulmonary and many other tissues. In spite of significant advances in the understanding how monomeric tropoelastin is assembled into the polymeric elastic matrix, details of this assembly process are still lacking. In particular it is not clear how the various architectures and more subtle elastic properties required by diverse elastic tissues can arise from the protein product of a single gene. While monomeric tropoelastin has the intrinsic ability to self-assem...
Source: Matrix Biology - June 26, 2019 Category: Molecular Biology Authors: Reichheld SE, Muiznieks LD, Lu R, Sharpe S, Keeley FW Tags: Matrix Biol Source Type: research

Non-invasive marker-independent high content analysis of a microphysiological human pancreas-on-a-chip model.
In this study, we developed an endocrine pancreas-on-a-chip model based on a tailored microfluidic platform, which enables self-guided trapping of single human pseudo-islets. Continuous, low-shear perfusion provides a physiologically relevant microenvironment especially important for modeling and monitoring of the endocrine function as well as sufficient supply with nutrients and oxygen. Human pseudo-islets, generated from the conditionally immortalized EndoC-βH3 cell line, were successfully injected by hydrostatic pressure-driven flow without altered viability. To track insulin secretion kinetics in response to gluco...
Source: Matrix Biology - June 22, 2019 Category: Molecular Biology Authors: Zbinden A, Marzi J, Schlünder K, Probst C, Urbanczyk M, Black S, Brauchle EM, Layland SL, Kraushaar U, Duffy G, Schenke-Layland K, Loskill P Tags: Matrix Biol Source Type: research

Elastic fibers and elastin receptor complex: Neuraminidase-1 takes the center stage.
Abstract Extracellular matrix (ECM) has for a long time being considered as a simple architectural support for cells. It is now clear that ECM presents a fundamental influence on cells driving their phenotype and fate. This complex network is highly specialized and the different classes of macromolecules that comprise the ECM determine its biological functions. For instance, collagens are responsible for the tensile strength of tissues, proteoglycans and glycosaminoglycans are essential for hydration and resistance to compression, and glycoproteins such as laminins facilitate cell attachment. The largest structure...
Source: Matrix Biology - June 18, 2019 Category: Molecular Biology Authors: Bennasroune A, Romier-Crouzet B, Blaise S, Laffargue M, Efremov RG, Martiny L, Maurice P, Duca L Tags: Matrix Biol Source Type: research

The role of fibrillin and microfibril binding proteins in elastin and elastic fibre assembly.
Abstract Fibrillin is a large evolutionarily ancient extracellular glycoprotein that assembles to form beaded microfibrils which are essential components of most extracellular matrices. Fibrillin microfibrils have specific biomechanical properties to endow animal tissues with limited elasticity, a fundamental feature of the durable function of large blood vessels, skin and lungs. They also form a template for elastin deposition and provide a platform for microfibril-elastin binding proteins to interact in elastic fibre assembly. In addition to their structural role, fibrillin microfibrils mediate cell signalling v...
Source: Matrix Biology - June 18, 2019 Category: Molecular Biology Authors: Godwin ARF, Singh M, Lockhart-Cairns MP, Alanazi Y, Cain SA, Baldock C Tags: Matrix Biol Source Type: research

Collagen XIII-derived ectodomain regulates bone angiogenesis and intracortical remodeling.
In this study, we found that ColXIII expression is significantly upregulated in osteoporotic patients. In view of that, we studied bone homeostasis in ColXIII-overexpressing mice (Col13a1oe) up to 72 weeks of age and observed a cortical bone overgrowth followed by a drastic bone loss, together with increased bone vascularization. Moreover, our results demonstrate that the ColXIII-derived ectodomain enhances angiogenesis through β1-integrins and the JNK pathway. Consequently, these data suggest that ColXIII has a role in age-dependent cortical bone deterioration with possible implications for osteoporosis and fractur...
Source: Matrix Biology - June 17, 2019 Category: Molecular Biology Authors: Koivunen J, Kemppainen AV, Finnilä MA, Keski-Filppula R, Härönen H, Tu H, Pellikka H, Heikkinen A, Kylmäoja E, Sormunen R, Miinalainen I, Saarakkala S, Izzi V, Pihlajaniemi T Tags: Matrix Biol Source Type: research

Tension in fibrils suppresses their enzymatic degradation - A molecular mechanism for 'use it or lose it'.
Abstract Tissue homeostasis depends on a balance of synthesis and degradation of constituent proteins, with use of a given protein potentially regulating its turnover. Extracellular matrix (ECM) is predominantly composed of fibrillar collagens that exhibit tension-sensitive degradation, which we review here at different levels of hierarchy. Past experiments and recent proteomics measurements together suggest that mechanical strain stabilizes collagen against enzymatic degradation at the scale of tissues and fibrils whereas isolated collagen molecules exhibit a biphasic behavior that depends on load magnitude. With...
Source: Matrix Biology - June 12, 2019 Category: Molecular Biology Authors: Saini K, Cho S, Dooling LJ, Discher DE Tags: Matrix Biol Source Type: research

Transcriptomic analysis reveals that BMP4 sensitizes glioblastoma tumor-initiating cells to mechanical cues.
Abstract The poor prognosis of glioblastoma (GBM) is associated with a highly invasive stem-like subpopulation of tumor-initiating cells (TICs), which drive recurrence and contribute to intra-tumoral heterogeneity through differentiation. These TICs are better able to escape extracellular matrix-imposed mechanical restrictions on invasion than their more differentiated progeny, and sensitization of TICs to extracellular matrix mechanics extends survival in preclinical models of GBM. However, little is known about the molecular basis of the relationship between TIC differentiation and mechanotransduction. Here we e...
Source: Matrix Biology - June 9, 2019 Category: Molecular Biology Authors: Hughes JH, Ewy JM, Chen J, Wong SY, Tharp KM, Stahl A, Kumar S Tags: Matrix Biol Source Type: research

Covalent cross-linking of basement membrane-like matrices physically restricts invasive protrusions in breast cancer cells.
Abstract The basement membrane (BM) provides a physical barrier to invasion in epithelial tumors, and alterations in the molecular makeup and structural integrity of the BM have been implicated in cancer progression. Invadopodia are the invasive protrusions that enable cancer cells to breach the nanoporous basement membrane, through matrix degradation and generation of force. However, the impact of covalent cross-linking on invadopodia extension into the BM remains unclear. Here, we examine the impact of covalent cross-linking of extracellular matrix on invasive protrusions using biomaterials that present ligands ...
Source: Matrix Biology - June 1, 2019 Category: Molecular Biology Authors: Wisdom KM, Indana D, Chou PE, Desai R, Kim T, Chaudhuri O Tags: Matrix Biol Source Type: research

Distinct glycosylation in membrane proteins within neonatal versus adult myocardial tissue.
In this study, glycosylation of the adult rat cardiac ventricle showed no variability between the two strains analysed, nor were there any differences between the glycosylation of the right or left ventricle using lectin histochemistry and microarray profiling. However, in the Sprague-Dawley strain, neonatal cardiac glycosylation in the left ventricle differed from adult tissues using mass spectrometric analysis, showing a higher expression of high mannose structures and lower expression of complex N-linked glycans in the three-day-old neonatal tissue. Man6GlcNAc2 was identified as the main high mannose N-linked structure ...
Source: Matrix Biology - May 17, 2019 Category: Molecular Biology Authors: Contessotto P, Ellis B, Jin C, Karlsson NG, Zorlutuna P, Kilcoyne M, Pandit A Tags: Matrix Biol Source Type: research

Bioengineered scaffolds for 3D culture demonstrate extracellular matrix-mediated mechanisms of chemotherapy resistance in glioblastoma.
Abstract Originating in the brain, glioblastoma (GBM) is a highly lethal and virtually incurable cancer, in large part because it readily develops resistance to treatments. While numerous studies have investigated mechanisms enabling GBM cells to evade chemotherapy-induced apoptosis, few have addressed how their surrounding extracellular matrix (ECM) acts to promote their survival. Here, we employed a biomaterial-based, 3D culture platform to investigate systematically how interactions between patient-derived GBM cells and the brain ECM promote resistance to alkylating chemotherapies - including temozolomide, whic...
Source: Matrix Biology - April 24, 2019 Category: Molecular Biology Authors: Xiao W, Wang S, Zhang R, Sohrabi A, Yu Q, Liu S, Ehsanipour A, Liang J, Bierman RD, Nathanson DA, Seidlits SK Tags: Matrix Biol Source Type: research

Citrullination of fibronectin alters integrin clustering and focal adhesion stability promoting stromal cell invasion.
Abstract The extracellular matrix (ECM) microenvironment is increasingly implicated in the instruction of pathologically relevant cell behaviors, from aberrant transdifferentation to invasion and beyond. Indeed, pathologic ECMs possess a panoply of alterations that provide deleterious instructions to resident cells. Here we demonstrate the precise manner in which the ECM protein fibronectin (FN) undergoes the posttranslational modification citrullination in response to peptidyl-arginine deiminase (PAD), an enzyme associated with innate immune cell activity and implicated in systemic ECM-centric diseases, like canc...
Source: Matrix Biology - April 17, 2019 Category: Molecular Biology Authors: Stefanelli VL, Choudhury S, Hu P, Liu Y, Schwenzer A, Yeh CR, Chambers DM, Pesson K, Li W, Segura T, Midwood KS, Torres M, Barker TH Tags: Matrix Biol Source Type: research

Engineering microenvironment for human cardiac tissue assembly in heart-on-a-chip platform.
Abstract Organ-on-a-chip systems have the potential to revolutionize drug screening and disease modeling through the use of human stem cell-derived cardiomyocytes. The predictive power of these tissue models critically depends on the functional assembly and maturation of human cells that are used as building blocks for organ-on-a-chip systems. To resemble a more adult-like phenotype on these heart-on-a-chip systems, the surrounding micro-environment of individual cardiomyocyte needs to be controlled. Herein, we investigated the impact of four microenvironmental cues: cell seeding density, types and percentages of ...
Source: Matrix Biology - April 11, 2019 Category: Molecular Biology Authors: Zhao Y, Rafatian N, Wang EY, Feric NT, Lai BFL, Knee-Walden EJ, Backx PH, Radisic M Tags: Matrix Biol Source Type: research

Elastic fibers and biomechanics of the aorta: Insights from mouse studies.
Abstract Elastic fibers are major components of the extracellular matrix (ECM) in the aorta and support a life-long cycling of stretch and recoil. Elastic fibers are formed from mid-gestation throughout early postnatal development and the synthesis is regulated at multiple steps, including coacervation, deposition, cross-linking, and assembly of insoluble elastin onto microfibril scaffolds. To date, more than 30 molecules have been shown to associate with elastic fibers and some of them play a critical role in the formation and maintenance of elastic fibers in vivo. Because the aorta is subjected to high pressure ...
Source: Matrix Biology - March 14, 2019 Category: Molecular Biology Authors: Yanagisawa H, Wagenseil J Tags: Matrix Biol Source Type: research

Thrombospondin-2 regulates extracellular matrix production, LOX levels, and cross-linking via downregulation of miR-29.
Abstract Collagen fibrillogenesis and crosslinking have long been implicated in extracellular matrix (ECM)-dependent processes such as fibrosis and scarring. However, the extent to which matricellular proteins influence ECM protein production and fibrillar collagen crosslinking has yet to be determined. Here we show that thrombospondin 2 (TSP2), an anti-angiogenic matricellular protein, is an important modulator of ECM homeostasis. Specifically, through a fractionated quantitative proteomics approach, we show that loss of TSP2 leads to a unique ECM phenotype characterized by a significant decrease in fibrillar col...
Source: Matrix Biology - March 12, 2019 Category: Molecular Biology Authors: Calabro NE, Barrett A, Chamorro-Jorganes A, Tam S, Kristofik NJ, Xing H, Loye AM, Sessa WC, Hansen K, Kyriakides TR Tags: Matrix Biol Source Type: research

p16Ink4a deletion in cells of the intervertebral disc affects their matrix homeostasis and senescence associated secretory phenotype without altering onset of senescence.
Abstract Intervertebral disc degeneration is an important contributor to chronic low back and neck pain. Although many environmental and genetic factors are known to contribute to disc degeneration, age is still the most significant risk factor. Recent studies have shown that senescence may play a role in age-related disc degeneration and matrix catabolism in humans and mouse models. Clearance of p16Ink4a-positive senescent cells reduces the degenerative phenotype in many age-associated diseases. Whether p16Ink4a plays a functional role in intervertebral disc degeneration and senescence is unknown. We first charac...
Source: Matrix Biology - February 24, 2019 Category: Molecular Biology Authors: Novais EM, Diekman BO, Shapiro IM, Risbud MV Tags: Matrix Biol Source Type: research

Hyaluronan biology: A complex balancing act of structure, function, location and context.
Abstract Cell-matrix interactions are fundamental to many developmental, homeostatic, immune and pathologic processes. Hyaluronan (HA), a critical component of the extracellular matrix (ECM) that regulates normal structural integrity and development, also regulates tissue responses during injury, repair and regeneration. Though simple in its primary structure, HA regulates biological responses in a highly complex manner with balanced contributions from its molecular size and concentration, synthesis versus enzymatic and/or oxidative-nitrative fragmentation, interactions with key HA binding proteins and cell associ...
Source: Matrix Biology - February 22, 2019 Category: Molecular Biology Authors: Garantziotis S, Savani RC Tags: Matrix Biol Source Type: research

Collagen fiber structure guides 3D motility of cytotoxic T lymphocytes.
Abstract Lymphocyte motility is governed by a complex array of mechanisms, and highly dependent on external microenvironmental cues. Tertiary lymphoid sites in particular have unique physical structure such as collagen fiber alignment, due to matrix deposition and remodeling. Three dimensional studies of human lymphocytes in such environments are lacking. We hypothesized that aligned collagenous environment modulates CD8+ T cells motility. We encapsulated activated CD8+ T cells in collagen hydrogels of distinct fiber alignment, a characteristic of tumor microenvironments. We found that human CD8+ T cells move fast...
Source: Matrix Biology - February 15, 2019 Category: Molecular Biology Authors: Pruitt HC, Lewis D, Ciccaglione M, Connor S, Smith Q, Hickey JW, Schneck JP, Gerecht S Tags: Matrix Biol Source Type: research

Limb- and tendon-specific Adamtsl2 deletion identifies a role for ADAMTSL2 in tendon growth in a mouse model for geleophysic dysplasia.
Abstract Geleophysic dysplasia is a rare, frequently lethal condition characterized by severe short stature with progressive joint contractures, cardiac, pulmonary, and skin anomalies. Geleophysic dysplasia results from dominant fibrillin-1 (FBN1) or recessive ADAMTSL2 mutations, suggesting a functional link between ADAMTSL2 and fibrillin microfibrils. Mice lacking ADAMTSL2 die at birth, which has precluded analysis of postnatal limb development and mechanisms underlying the skeletal anomalies of geleophysic dysplasia. Here, detailed expression analysis of Adamtsl2 using an intragenic lacZ reporter shows strong Ad...
Source: Matrix Biology - February 7, 2019 Category: Molecular Biology Authors: Hubmacher D, Taye N, Balic Z, Thacker S, Adams SM, Birk DE, Schweitzer R, Apte SS Tags: Matrix Biol Source Type: research

Denervation-induced skeletal muscle fibrosis is mediated by CTGF/CCN2 independently of TGF- β.
Denervation-induced skeletal muscle fibrosis is mediated by CTGF/CCN2 independently of TGF-β. Matrix Biol. 2019 Feb 01;: Authors: Rebolledo DL, González D, Faundez-Contreras J, Contreras O, Vio CP, Murphy-Ullrich JE, Lipson KE, Brandan E Abstract Muscular fibrosis is caused by excessive accumulation of extracellular matrix (ECM) that replaces functional tissue, and it is a feature of several myopathies and neuropathies. Knowledge of the biology and regulation of pro-fibrotic factors is critical for the development of new therapeutic strategies. Upon unilateral sciatic nerve transection, we...
Source: Matrix Biology - February 1, 2019 Category: Molecular Biology Authors: Rebolledo DL, González D, Faundez-Contreras J, Contreras O, Vio CP, Murphy-Ullrich JE, Lipson KE, Brandan E Tags: Matrix Biol Source Type: research