Tendon Extracellular Matrix Remodeling and Defective Cell Polarization in the Presence of Collagen VI Mutations
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Assembly of Fibrillin Microfibrils Governs Extracellular Deposition of Latent TGF
3006 Research Article Assembly of fibrillin microfibrils governs extracellular deposition of latent TGF Teresa Massam-Wu*, Maybo Chiu*, Rawshan Choudhury, Shazia S. Chaudhry, Andrew K. Baldwin, Amanda McGovern, Clair Baldock, C. Adrian Shuttleworth and Cay M. Kielty‡ Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK *These authors contributed equally to this work ‡Author for correspondence ([email protected]) Accepted 18 May 2010 Journal of Cell Science 123, 3006-3018 © 2010. Published by The Company of Biologists Ltd doi:10.1242/jcs.073437 Summary Control of the bioavailability of the growth factor TGF is essential for tissue formation and homeostasis, yet precisely how latent TGF is incorporated into the extracellular matrix is unknown. Here, we show that deposition of a large latent TGF complex (LLC), which contains latent TGF-binding protein 1 (LTBP-1), is directly dependent on the pericellular assembly of fibrillin microfibrils, which interact with fibronectin during higher-order fibrillogenesis. LTBP-1 formed pericellular arrays that colocalized with microfibrils, whereas fibrillin knockdown inhibited fibrillar LTBP-1 and/or LLC deposition. Blocking 51 integrin or supplementing cultures with heparin, which both inhibited microfibril assembly, disrupted LTBP-1 deposition and enhanced Smad2 phosphorylation. Full-length LTBP-1 bound only weakly to N-terminal pro-fibrillin-1, but this association was strongly enhanced by heparin. The microfibril- associated glycoprotein MAGP-1 (MFAP-2) inhibited LTBP-1 binding to fibrillin-1 and stimulated Smad2 phosphorylation. By contrast, fibulin-4, which interacted strongly with full-length LTBP-1, did not induce Smad2 phosphorylation. -
Tendon Fibroblasts
Ann Rheum Dis: first published as 10.1136/ard.46.5.385 on 1 May 1987. Downloaded from Annals of the Rheumatic Diseases, 1987; 46, 385-390 Isolation and growth characteristics of adult human tendon fibroblasts M D CHARD, J K WRIGHT, AND B L HAZLEMAN From the Rheumatology Research Unit, Addenbrooke's Hospital, Hills Road, Cambridge SUMMARY An explant method for the isolation of fibroblasts from adult human tendon is described. Cells were successfully isolated from 22 out of 27 common biceps tendons obtained from cadaveric donors (age range 11-83 years). The fibroblasts could be maintained in culture using standard methods and morphologically resembled those of synovial rather than dermal origin. Growth characteristics of 12 cell lines were assessed by deoxyribose nucleic acid (DNA) synthesis using [3H]thymidine incorporation in response to stimulation by fetal calf serum. Cells obtained separately from superficial and deep parts of the tendons produced almost identical responses. No significant reduction in growth response with increasing age was found when related to the age of the donor. Therefore this study did not show any age related defect in the short term tendon fibroblast replicative responses to serum. Key words: in vitro, DNA synthesis. copyright. Tendinous lesions are common, but their nature and other tissues such as skin. It is desirable to investi- any possible predisposing factors are not well gate adult human tendon fibroblasts directly. It was understood. They occur in middle life frequently thought that the culture of adult human tendon after only minor, if any, injury. The extent to which fibroblasts would be very difficult to achieve be- this reflects age related changes in tendon tissue is cause of the differentiated appearance of cells on uncertain. -
Review the Cellular Matrix: a Feature of Tensile Bearing Dense Soft
Histol Histopathol (2002) 17: 523-537 Histology and http://www.hh.um.es Histopathology Cellular and Molecular Biology Review The cellular matrix: a feature of tensile bearing dense soft connective tissues I.K. Lo, S. Chi, T. Ivie, C.B. Frank and J.B. Rattner Joint Injury and Arthritis Research Group, University of Calgary, Calgary, Canada S u m m a r y. The term connective tissue encompasses a recent studies using a variety of microscopic and indirect d iverse group of tissues that reside in diff e r e n t immunofluorescence techniques suggest that these e nvironments and must support a spectrum of apparently diverse groups of tissues, which are mechanical functions. Although the extracellular matrix characterized by a spectrum of functions and in vivo of these tissues is well described, the cellular mechanical environments, are organized around similar architecture of these tissues and its relationship to tissue architectural principles. function has only recently become the focus of study. It The purpose of this rev i ew is to highlight recent n ow appears that tensile-bearing dense connective d evelopments in our understanding of the cellular tissues may be a specific class of connective tissues that architecture of dense soft connective tissues and to display a common cellular organization characterized by discuss their functional implications. It will become fusiform cells with cytoplasmic projections and ga p clear that a 3-dimensional cellular arrangement, a junctions. These cells with their cellular projections are “cellular matrix”, consisting of fusiform cells with organised into a complex 3-dimensional network leading cytoplasmic projections and gap junctions may define a to a phy s i c a l l y, chemically and electrically connected s p e c i fic class of hy p o c e l l u l a r, tensile-bearing, dense cellular matrix. -
Collagen VI-Related Myopathy
Collagen VI-related myopathy Description Collagen VI-related myopathy is a group of disorders that affect skeletal muscles (which are the muscles used for movement) and connective tissue (which provides strength and flexibility to the skin, joints, and other structures throughout the body). Most affected individuals have muscle weakness and joint deformities called contractures that restrict movement of the affected joints and worsen over time. Researchers have described several forms of collagen VI-related myopathy, which range in severity: Bethlem myopathy is the mildest, an intermediate form is moderate in severity, and Ullrich congenital muscular dystrophy is the most severe. People with Bethlem myopathy usually have loose joints (joint laxity) and weak muscle tone (hypotonia) in infancy, but they develop contractures during childhood, typically in their fingers, wrists, elbows, and ankles. Muscle weakness can begin at any age but often appears in childhood to early adulthood. The muscle weakness is slowly progressive, with about two-thirds of affected individuals over age 50 needing walking assistance. Older individuals may develop weakness in respiratory muscles, which can cause breathing problems. Some people with this mild form of collagen VI-related myopathy have skin abnormalities, including small bumps called follicular hyperkeratosis on the arms and legs; soft, velvety skin on the palms of the hands and soles of the feet; and abnormal wound healing that creates shallow scars. The intermediate form of collagen VI-related myopathy is characterized by muscle weakness that begins in infancy. Affected children are able to walk, although walking becomes increasingly difficult starting in early adulthood. They develop contractures in the ankles, elbows, knees, and spine in childhood. -
The Beneficial Regulation of Extracellular Matrix
cosmetics Article The Beneficial Regulation of Extracellular Matrix and Heat Shock Proteins, and the Inhibition of Cellular Oxidative Stress Effects and Inflammatory Cytokines by 1α, 25 dihydroxyvitaminD3 in Non-Irradiated and Ultraviolet Radiated Dermal Fibroblasts Neena Philips *, Xinxing Ding, Pranathi Kandalai, Ilonka Marte, Hunter Krawczyk and Richard Richardson School of Natural Sciences, Fairleigh Dickinson University, Teaneck, NJ 07601, USA * Correspondence: [email protected] or [email protected] Received: 30 June 2019; Accepted: 20 July 2019; Published: 1 August 2019 Abstract: Intrinsic skin aging and photoaging, from exposure to ultraviolet (UV) radiation, are associated with altered regulation of genes associated with the extracellular matrix (ECM) and inflammation, as well as cellular damage from oxidative stress. The regulatory properties of 1α, 25dihydroxyvitamin D3 (vitamin D) include endocrine, ECM regulation, cell differentiation, photoprotection, and anti-inflammation. The goal of this research was to identify the beneficial effects of vitamin D in preventing intrinsic skin aging and photoaging, through its direct effects as well as its effects on the ECM, associated heat shock proteins (HSP-47, and -70), cellular oxidative stress effects, and inflammatory cytokines [interleukin (IL)-1 and IL-8] in non-irradiated, UVA-radiated, UVB-radiated dermal fibroblasts. With regard to the ECM, vitamin D stimulated type I collagen and inhibited cellular elastase activity in non-irradiated fibroblasts; and stimulated type I collagen and HSP-47, and inhibited elastin expression and elastase activity in UVA-radiated dermal fibroblasts. With regard to cellular protection, vitamin D inhibited oxidative damage to DNA, RNA, and lipids in non-irradiated, UVA-radiated and UVB-radiated fibroblasts, and, in addition, increased cell viability of UVB-radiated cells. -
Dietary Protein Restriction Rapidly Reduces Transforming Growth Factor
Proc. Natl. Acad. Sci. USA Vol. 88, pp. 9765-9769, November 1991 Medical Sciences Dietary protein restriction rapidly reduces transforming growth factor p1 expression in experimental glomerulonephritis (extraceliular matrix/transforming growth factor 8/glomerulonephritis) SEIYA OKUDA*, TAKAMICHI NAKAMURA*, TATSUO YAMAMOTO*, ERKKI RUOSLAHTIt, AND WAYNE A. BORDER*t *Division of Nephrology, University of Utah School of Medicine, Salt Lake City, UT 84132; and tCancer Research Center, La Jolla Cancer Research Foundation, La Jolla, CA 92037 Communicated by Eugene Roberts, August 19, 1991 (receivedfor review April 29, 1991) ABSTRACT Dietary protein restriction has been shown to TGF-/31 on both cell types is to regulate the synthesis of two slow the rate of loss of kidney function in humans with chondroitin/dermatan sulfate proteoglycans, biglycan and progressive glomerulosclerosis due to glomerulonephritis or decorin, both of which can bind TGF-P1 (23). In an experi- diabetes mellitus. A central feature of glomerulosclerosis is the mental model ofglomerulonephritis in the rat, we have found pathological accumulation of extracellular matrix within the a close association between elevated expression of the diseased glomeruli. Transforming growth factor j1 (TGF-.81) TGF-131 gene and the development of glomerulonephritis is known to have widespread regulatory effects on extracellular (10). Seven days after glomerular injury, at the time of matrix and has been implicated as a major cause of increased significant extracellular matrix accumulation, the glomeruli extracellular matrix synthesis and buildup of pathological showed a 5-fold increase in TGF-f31 mRNA and a nearly matrix within glomeruli in experimental glomerulonephritis. 50-fold increase in production ofbiglycan and decorin. -
Extracellular Matrix Grafts: from Preparation to Application (Review)
INTERNATIONAL JOURNAL OF MOleCular meDICine 47: 463-474, 2021 Extracellular matrix grafts: From preparation to application (Review) YONGSHENG JIANG1*, RUI LI1,2*, CHUNCHAN HAN1 and LIJIANG HUANG1 1Science and Education Management Center, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, Zhejiang 315700; 2School of Chemistry, Sun Yat-sen University, Guangzhou, Guangdong 510275, P.R. China Received July 30, 2020; Accepted December 3, 2020 DOI: 10.3892/ijmm.2020.4818 Abstract. Recently, the increasing emergency of traffic acci- Contents dents and the unsatisfactory outcome of surgical intervention are driving research to seek a novel technology to repair trau- 1. Introduction matic soft tissue injury. From this perspective, decellularized 2. ECM-G characterization matrix grafts (ECM-G) including natural ECM materials, and 3. Methods of decellularization treatments their prepared hydrogels and bioscaffolds, have emerged as 4. Removal of residual cellular components and chemicals possible alternatives for tissue engineering and regenerative 5. Application of ECM-P in regenerative medicine medicine. Over the past decades, several physical and chemical 6. Challenges and future outlook on ECM-P decellularization methods have been used extensively to deal 7. Conclusions with different tissues/organs in an attempt to carefully remove cellular antigens while maintaining the non-immunogenic ECM components. It is anticipated that when the decellular- 1. Introduction ized biomaterials are seeded with cells in vitro or incorporated into irregularly shaped defects in vivo, they can provide the The extracellular matrix (ECM) derived from organs/tissues is appropriate biomechanical and biochemical conditions for a complex, highly organized assembly of macromolecules with directing cell behavior and tissue remodeling. -
Comparative Multi-Scale Hierarchical Structure of the Tail, Plantaris, and Achilles Tendons in 2 the Rat 3 Andrea H
bioRxiv preprint doi: https://doi.org/10.1101/396309; this version posted August 20, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 Comparative Multi-scale Hierarchical Structure of the Tail, Plantaris, and Achilles Tendons in 2 the Rat 3 Andrea H. Lee, Dawn M. Elliott* 4 Department of Biomedical Engineering, University of Delaware 5 *Corresponding author. Tel.: +1 302 831 1295. E-mail address: [email protected] (D.M. Elliott). 6 7 Keyword: Tendon, Hierarchical Structure, Multi-scale, Imaging 8 9 10 Abstract (500 words) 11 Rodent tendons are widely used to study human pathology, such as tendinopathy and 12 repair, and to address fundamental physiological questions about development, growth, and 13 remodeling. However, how the gross morphology and the multi-scale hierarchical structure of 14 rat tendons, such as the tail, plantaris, and Achillles tendons, compare to that of human 15 tendons are unknown. In addition, there remains disagreement about terminology and 16 definitions. Specifically, the definition of fascicle and fiber are often dependent on the diameter 17 size and not their characteristic features, which impairs the ability to compare across species 18 where the size of the fiber and fascicle might change with animal size and tendon function. 19 Thus, the objective of the study was to select a single species that is widely used for tendon 20 research (rat) and tendons with varying mechanical functions (tail, plantaris, Achilles) to 21 evaluate the hierarchical structure at multiple length scales. -
New Insights Into the Secretory Functions of Brown Adipose Tissue
243 2 Journal of J Villarroya et al. Secretory functions of brown 243:2 R19–R27 Endocrinology adipose tissue REVIEW New insights into the secretory functions of brown adipose tissue Joan Villarroya, Rubén Cereijo, Aleix Gavaldà-Navarro, Marion Peyrou, Marta Giralt and Francesc Villarroya Departament de Bioquímica i Biomedicina Molecular and Institut de Biomedicina (IBUB), Universitat de Barcelona, Barcelona, Catalonia, Spain CIBER Fisiopatología de la Obesidad y Nutrición, Barcelona, Catalonia, Spain Correspondence should be addressed to F Villarroya: [email protected] Abstract In recent years, an important secretory role of brown adipose tissue (BAT) has emerged, Key Words which is consistent, to some extent, with the earlier recognition of the important f brown adipose tissue secretory role of white fat. The so-called brown adipokines or ‘batokines’ may play an f brown adipokine autocrine role, which may either be positive or negative, in the thermogenic function f batokine of brown adipocytes. Additionally, there is a growing recognition of the signalling f thermogenesis molecules released by brown adipocytes that target sympathetic nerve endings (such as neuregulin-4 and S100b protein), vascular cells (e.g., bone morphogenetic protein-8b), and immune cells (e.g., C-X-C motif chemokine ligand-14) to promote the tissue remodelling associated with the adaptive BAT recruitment in response to thermogenic stimuli. Moreover, existing indications of an endocrine role of BAT are being confirmed through the release of brown adipokines acting on other distant tissues and organs; a recent example is the recognition that BAT-secreted fibroblast growth factor-21 and myostatin target the heart and skeletal muscle, respectively. -
Effects of Collagen-Derived Bioactive Peptides and Natural Antioxidant
www.nature.com/scientificreports OPEN Efects of collagen-derived bioactive peptides and natural antioxidant compounds on Received: 29 December 2017 Accepted: 19 June 2018 proliferation and matrix protein Published: xx xx xxxx synthesis by cultured normal human dermal fbroblasts Suzanne Edgar1, Blake Hopley1, Licia Genovese2, Sara Sibilla2, David Laight1 & Janis Shute1 Nutraceuticals containing collagen peptides, vitamins, minerals and antioxidants are innovative functional food supplements that have been clinically shown to have positive efects on skin hydration and elasticity in vivo. In this study, we investigated the interactions between collagen peptides (0.3–8 kDa) and other constituents present in liquid collagen-based nutraceuticals on normal primary dermal fbroblast function in a novel, physiologically relevant, cell culture model crowded with macromolecular dextran sulphate. Collagen peptides signifcantly increased fbroblast elastin synthesis, while signifcantly inhibiting release of MMP-1 and MMP-3 and elastin degradation. The positive efects of the collagen peptides on these responses and on fbroblast proliferation were enhanced in the presence of the antioxidant constituents of the products. These data provide a scientifc, cell-based, rationale for the positive efects of these collagen-based nutraceutical supplements on skin properties, suggesting that enhanced formation of stable dermal fbroblast-derived extracellular matrices may follow their oral consumption. Te biophysical properties of the skin are determined by the interactions between cells, cytokines and growth fac- tors within a network of extracellular matrix (ECM) proteins1. Te fbril-forming collagen type I is the predomi- nant collagen in the skin where it accounts for 90% of the total and plays a major role in structural organisation, integrity and strength2. -
Establishment and Investigation of Tendon-Derived Cell Lines Immortalized by the Human Telomerase Reverse Transcriptase Gene
Aus der Chirurgischen Klinik und Poliklinik – Innenstadt, der Ludwig-Maximilians-Universität München Direktor: Prof. Dr. med. Wolf Mutschler Establishment and investigation of tendon- derived cell lines immortalized by the human telomerase reverse transcriptase gene. DISSERTATION zum Erwerb des Doktorgrades der Medizin an der Medizinischen Fakultät der Ludwig-Maximilians-Universität zu München vorgelegt von: Sophia Amina Poppe aus München, im Jahr 2010 Mit Genehmigung der Medizinischen Fakultät der Universität München Berichterstatter: Prof. Dr. med. Matthias Schieker Mitberichterstatter: Prof. Dr. Günther Eißner Prof. Dr. Peter Müller Mitbetreuung durch die promovierten Mitarbeiter: Dr. rer. nat. Denitsa Docheva Dekan: Prof. Dr. med. Dr. h.c. M. Reiser FACR, FRCR Tag der mündlichen Prüfung: 08. Juli 2010 1. INTRODUCTION......................................................................................................................... 4 1.1. General background......................................................................................................... 4 1.1.1. Anatomical and molecular structure of tendons.............................................. 4 1.1.1.1. Tendinous tissue................................................................................................ 4 1.1.1.2. Osteotendinous junction - enthesis............................................................ 5 1.1.1.3. Myotendinous junction................................................................................... 7 1.1.2. Development of tendons...................................................................................... -
Altered Adipose Tissue and Adipocyte Function in the Pathogenesis of Metabolic Syndrome
Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome C. Ronald Kahn, … , Guoxiao Wang, Kevin Y. Lee J Clin Invest. 2019;129(10):3990-4000. https://doi.org/10.1172/JCI129187. Review Series Over the past decade, great progress has been made in understanding the complexity of adipose tissue biology and its role in metabolism. This includes new insights into the multiple layers of adipose tissue heterogeneity, not only differences between white and brown adipocytes, but also differences in white adipose tissue at the depot level and even heterogeneity of white adipocytes within a single depot. These inter- and intra-depot differences in adipocytes are developmentally programmed and contribute to the wide range of effects observed in disorders with fat excess (overweight/obesity) or fat loss (lipodystrophy). Recent studies also highlight the underappreciated dynamic nature of adipose tissue, including potential to undergo rapid turnover and dedifferentiation and as a source of stem cells. Finally, we explore the rapidly expanding field of adipose tissue as an endocrine organ, and how adipose tissue communicates with other tissues to regulate systemic metabolism both centrally and peripherally through secretion of adipocyte-derived peptide hormones, inflammatory mediators, signaling lipids, and miRNAs packaged in exosomes. Together these attributes and complexities create a robust, multidimensional signaling network that is central to metabolic homeostasis. Find the latest version: https://jci.me/129187/pdf REVIEW SERIES: MECHANISMS UNDERLYING THE METABOLIC SYNDROME The Journal of Clinical Investigation Series Editor: Philipp E. Scherer Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome C. Ronald Kahn,1 Guoxiao Wang,1 and Kevin Y.