Extracellular Matrix News Volume 8.22 | Jun 8 2017

TOP STORY

Young at Heart: Restoring Cardiac Function with a Matrix Molecule

Scientists have uncovered a molecule in newborn hearts that appears to control the renewal process. When injected into adult mouse hearts injured by heart attacks, this molecule, called Agrin, seems to “unlock” that renewal process and enable heart muscle repair. [Press release from the Weizmann Institute of Science discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Preventing Tissue Fibrosis by Local Biomaterials Interfacing of Specific Cryptic Extracellular Matrix Information

Researchers developed an electrospun membrane biofunctionalized with a fragment of the laminin β1-chain to modulate the expression of matrix metalloproteinase 2 (MMP2). They demonstrated that interfacing of the β1-fragment with the mesothelium of the peritoneal membrane via a biomaterial abrogated the release of active MMP2 in response to transforming growth factor β1 and rescued tissue integrity ex vivo and in vivo in a mouse model of peritoneal fibrosis. [Nat Commun] Full Article

Laminin-111 and the Level of Nuclear Actin Regulate Epithelial Quiescence via Exportin-6

The authors showed previously that nuclear actin (N-actin) levels mediate the growth and quiescence of mouse epithelial cells in response to laminin-111 (LN1), a component of the mammary basement membrane. They showed that it is the LN1/N-actin pathway that is aberrant in human breast cancer cells, leading to continuous growth. [Cell Rep] Full Article | Graphical Abstract

Integrin-Linked Kinase Regulates Bone Formation by Controlling Cytoskeletal Organization and Modulating BMP and Wnt Signaling in Osteoprogenitors

To assess the in vivo role of integrin-linked kinase (ILK) signaling in osteoprogenitors and the osteoblast lineage cells descending thereof, investigators generated conditional knockout mice using the Osx-Cre:GFP driver strain. Mice lacking functional ILK in osterix-expressing cells and their derivatives showed no apparent developmental or growth phenotype, but by five weeks of age they displayed a significantly reduced trabecular bone mass, which persisted into adulthood in male mice. [J Bone Miner Res] Abstract

Wnt5a Induces Catabolic Signaling and Matrix Metalloproteinase Production in Human Articular Chondrocytes

Researchers investigated the role of Wnt5a as a potential mediator of cartilage destruction in osteoarthritis (OA). Cultured normal human chondrocytes were treated with fibronectin fragments (FN-f) as a catabolic stimulus or recombinant Wnt5a protein with or without pretreatment using a panel of signaling inhibitors. Wnt5a was present in human articular cartilage with OA changes and its expression and secretion were increased in FN-f stimulated chondrocytes. [Osteoarthritis Cartilage] Abstract

TGF-β1 Improves Biomechanical Strength by Extracellular Matrix Accumulation without Increasing the Number of Tenogenic Lineage Cells in a Rat Rotator Cuff Repair Model

The effects of transforming growth factor β1 (TGF-β1) on rotator cuff healing were investigated at 2, 4, 6, 8, and 12 weeks postoperatively. The TGF-β1-treated group had significantly higher ultimate load to failure and tissue volume at 6 and 12 weeks postoperatively and a higher collagen content at 12 weeks compared with the saline group. [Am J Sports Med] Abstract

Osteoblast-Derived Laminin-332 Is a Novel Negative Regulator of Osteoclastogenesis in Bone Microenvironments

Investigators found that laminin-332 (Lm-332) was expressed in osteoblasts, and was implicated in the regulation of osteoclast differentiation. Lm-332 markedly inhibited osteoclastogenesis induced by receptor activator of nuclear factor kappa B ligand when bone marrow-derived macrophages were cultured on Lm-332-coated plates. [Lab Invest] Abstract

Nicotine Stimulates Collagen Type I Expression in Lung via α7 Nicotinic Acetylcholine Receptors

Pulmonary fibroblasts from wildtype and α7 nicotinic acetylcholine receptor knockout mice were exposed to nicotine and examined for collagen type 1 mRNA and protein expression. Scientists found that nicotine stimulated collagen type I mRNA and protein expression in a dose-dependent manner and up to 72 hours in primary lung fibroblasts. [Respir Res] Full Article

Native Extracellular Matrix/Fibroin Hydrogels for Adipose Tissue Engineering with Enhanced Vascularization

Researchers developed thick and vascularized adipose tissue constructs supporting cell viability and adipose tissue regeneration. Gelation times decreased with increasing fibroin ratio among hydrogel groups 1:3 decellularized adipose tissue (DAT):fibroin (Fib) ratio group showed similar mechanical properties with adipose tissue. In vitro analyses showed that hydrogels with 1:3 DAT:Fib ratio supported better cell viability. [Biomed Mater] Abstract

Endothelial to Mesenchymal Transformation is Induced by Altered Extracellular Matrix in Aortic Valve Endothelial Cells

Investigators developed in vitro models of early and late-stage valve disease by incorporating the glycosaminoglycans (GAGs) chondroitin sulfate (CS), hyaluronic acid and dermatan sulfate into 3D collagen hydrogels with or without exposure to TGF-β1 to simulate endothelial to mesenchymal transformation (EndMT) in response to microenvironmental changes. High levels of CS induced the highest rate of EndMT and led to the most collagen I and GAG production by mesenchymally transformed cells, which indicates a cell phenotype most likely to promote fibrotic disease. [J Biomed Mater Res A] Abstract

Mechanosensing of Matrix by Stem Cells: From Contractility and Matrix Heterogeneity to Cardiogenesis and Muscle Stem Cells

The authors focus on mechanosensing of matrix elasticity in the differentiation or early maturation of a few illustrative stem cell types, with an intended audience of biologists and physical scientists. Contractile forces applied by a cell’s acto-myosin cytoskeleton are often resisted by the extracellular matrix and transduced through adhesions and the cytoskeleton ultimately into the nucleus to modulate gene expression. [Semin Cell Dev Biol] Abstract

Metalloproteinases in Extracellular Vesicles

Researchers focus on recent findings and knowledge about metalloproteinases in extracellular vesicle biology, and they discuss their potential involvement in human diseases, highlighting the context of tumor cells and their microenvironment. [Biochim Biophys Acta] Abstract

Visit our reviews page to see a complete list of reviews in the extracellular matrix research field.

Yale School of Medicine Expands Partnership to Promote Clinical Trials and Training in Puerto Rico

An expanded partnership between the Yale School of Medicine and research institutions in Puerto Rico is set to foster collaborative clinical research and training opportunities in both countries. [Yale University] Press Release

Fibrocell Completes Dosing of First Cohort in Phase I/II Clinical Trial of FCX-007 Gene Therapy for Treatment of Recessive Dystrophic Epidermolysis Bullosa

Fibrocell Science, Inc. announced that the remaining two patients in the NC1⁺ cohort have been dosed in the Phase I portion of the Phase I/II clinical trial of FCX-007 for the treatment of Recessive Dystrophic Epidermolysis Bullosa. [Fibrocell Science, Inc.] Press Release

NSF Offers Arm’s-Length Defense of Trump’s 2018 Request

President Donald Trump’s proposal for an 11.3% cut in spending at the National Science Foundation (NSF) may be dead on arrival in Congress. But that doesn’t mean congressional appropriators will be able to avoid any squeeze on NSF’s budget. Representative John Culberson, who chairs the House of Representatives spending panel that oversees NSF, opened a hearing yesterday on NSF’s 2018 budget request by saying he will work “to ensure NSF is appropriately funded” in the fiscal year. But after the hearing, Culberson declined to say whether that would require preserving its 2017 budget of $7.47 billion. [ScienceInsider] Editorial

Critics Challenge NIH Finding that Bigger Labs Aren’t Necessarily Better

A strident debate has erupted among biomedical researchers over a proposed National Institutes of Health (NIH) policy that would shift money from richer to poorer labs. The policy—which would limit investigators to the equivalent of three NIH grants—is based largely on an agency-led analysis of lab productivity. It found that once an NIH-funded lab grows to a certain size, each additional grant produces a smaller productivity boost. But NIH’s study, and one graph in particular, has drawn widespread criticism. [ScienceInsider] Editorial

Trump Retains Collins as NIH Director

President Donald Trump announced that he is keeping Francis Collins as director of the National Institutes of Health (NIH). Collins, who was appointed by former President Barack Obama in 2009, was asked to stay on temporarily after the election. The decision comes despite a recent call from some conservative members of Congress to fire Collins because he supports embryonic stem cell research. Collins has said he would return to full-time research if Trump asked him to step down. [ScienceInsider] Editorial

Romania’s Science Reforms Prompt Boycott

Researchers in Romania are stepping up protests against controversial government science reforms. Hundreds of scientists at leading research institutions say they will refuse to sit on national panels that assess and award grants, after the Romanian researchers’ association Ad Astra called for the boycott. But not all scientists in the country support the move. [Nature News] Editorial

NEW Quantitative Principles in Biology
November 2-4, 2017
Heidelberg, Germany

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NEW Group Leaders – Multiple Areas (French National Center for Scientific Research)

Assistant Professor – Biofilms (University of Maryland)

Postdoctoral Researcher – Degenerative Disc Disease (NUI Galway)

Part Time Faculty – Developmental Biology (Boston College Biology Department)

Assistant Professor – Genetics (University of Trento)

Postdoctoral Fellow – Proteoglycan Remodeling (University of Alberta)

Postdoctoral Research Fellow – Tendon and Connective Tissue Biology (Weill Cornell Medical College)

Postdoctoral Associate – Molecular and Cell Biology (Stony Brook University)

PhD Position – Extracellular Matrix in Cancer Progression (University of Copenhagen)

Biomaterials Scientist – Tissue Engineering (VitroLabs Inc.)

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